Insight into trifluoromethylation – experimental electron density for Togni reagent I

3,3-Dimethyl-1-(trifluoromethyl)-1,3-dihydro-1-λ3,2-benziodoxole represents a popular reagent for trifluoromethylation. The σ hole on the hypervalent iodine atom in this “Togni reagent” is crucial for adduct formation between the reagent and a nucleophilic substrate. The electronic situation may be probed by high resolution X-ray diffraction: the experimental charge density thus derived shows that the short intermolecular contact of 3.0 Å between the iodine and a neighbouring oxygen atom is associated with a local charge depletion on the heavy halogen in the direction of the nucleophile and visible polarization of the O valence shell towards the iodine atom. In agreement with the expectation for λ3-iodanes, the intermolecular O⋯I–C_aryl halogen bond deviates significantly from linearity.

The experimentally observed electron density for the “Togni reagent” explains the interaction of the hypervalent iodine atom with a nucleophile.

A “halogen bond” denotes a short contact between a nucleophile acting as electron density donor and a (mostly heavy) halogen atom as electrophile;^1,2 halogen bonds are a special of σ hole interactions.^3–5 Such interactions do not only play an important role in crystal engineering;^6–11 rather, the concept of a nucleophile approaching the σ hole of a neighbouring atom may also prove helpful for understanding chemical reactivity.The title compound provides an example for such a σ hole based reactivity: 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1-λ3,2-benziodoxole, 1, (Scheme 1) commonly known as “Togni reagent I”, is used for the electrophilic transfer of a trifluoromethyl group by reductive elimination. The original articles in which the application of 1¹² and other closely related “Togni reagents”¹³ were communicated have been and still are highly cited. Trifluoromethylation is not the only application for hypervalent iodine compounds; they have also been used as alkynylating¹⁴ or azide transfer reagents.^15,16 The syntheses of hypervalent iodanes and their application in organofluorine chemistry have been reviewed,¹⁷ and a special issues of the Journal of Organic Chemistry has been dedicated to Hypervalent Iodine Catalysis and Reagents.¹⁸ Recently, Pietrasiak and Togni have expanded the concept of hypervalent reagents to tellurium.¹⁹Open in a separate windowScheme 1Lewis structure of the Togni reagent, 1.Results from theory link σ hole interactions and chemical properties and indicate that the electron density distribution associated with the hypervalent iodine atom in 1 is essential for the reactivity of the molecule in trifluoromethylation.²⁰ Lüthi and coworkers have studied solvent effects and shown that activation entropy and volume play relevant roles for assigning the correct reaction mechanism to trifluoromethylation via1. These authors have confirmed the dominant role of reductive elimination and hence the relevance of the σ hole interaction for the reactivity of 1 in solution by ab initio molecular dynamics (AIMD) simulations.^21,22 An experimental approach to the electron density may complement theoretical calculations: low temperature X-ray diffraction data of sufficient resolution allow to obtain the experimental charge density and associate it with intra- and inter-molecular interactions.^23–25 Such advanced structure models based on aspherical scattering factors have also been applied in the study of halogen bonds.^26–30 In this contribution, we provide direct experimental information for the electronic situation in Togni reagent I, 1; in particular, we analyze the charge distribution around the hypervalent iodine atom.Excellent single crystals of the title compound were grown by sublimation.^§ The so-called independent atom model (IAM), i.e. the structure model based on conventional spherical scattering factors for neutral atoms, confirms the solid state structure reported by the original authors,¹² albeit with increased accuracy. As depicted in Fig. 1, two molecules of 1 interact via a crystallographic center of inversion. The pair of short intermolecular O⋯I contacts thus generated can be perceived as red areas on the interaction-sensitive Hirshfeld surface.³¹Open in a separate windowFig. 1Two neighbouring molecules of 1, related by a crystallographic center of inversion. The short intermolecular I⋯O contacts show up in red on the Hirshfeld surface³² enclosing the left molecule. (90% probability ellipsoids, H atoms omitted, symmetry operator 1 − x, 1 − y, 1 − z).The high resolution of our diffraction data ^¶ for 1 allowed an atom-centered multipole refinement^33,34 and thus an improved model for the experimental electron density which takes features of chemical bonding and lone pairs into account. Fig. 2 shows the deformation density, i.e. the difference electron density between this advanced multipole model and the IAM in the same orientation as Fig. 1.^|| The orientation of an oxygen lone pair (blue arrow) pointing towards the σ hole of the heavy halogen in the inversion-related molecule and the region of positive charge at this iodine atom (red arrow) are clearly visible. Single-bonded terminal halides are associated with one σ hole opposite to the only σ bond, thus resulting in a linear arrangement about the halogen atom. Different geometries and potentially more than a single σ hole are to be expected for λ3-iodanes such as our target molecule, and as a tendency, the resulting halogen bonds are expected to be weaker than those subtended by single-bonded iodine atoms.³⁵ In agreement with these theoretical considerations, the closest I⋯O contacts in 1 amount to 2.9822(9) Å. This distance is significantly shorter than the sum of the van-der-Waals radii (I, 1.98 Å; O, 1.52 Å (ref. 36)) but cannot compete with the shortest halogen bonds between iodine and oxygen^37,38 or iodine and nitrogen.^39–41Fig. 1 and ​and22 show that the C_aryl–I⋯O contacts are not linear; they subtend an angle C10–I1⋯O1′ of 141.23(3)° at the iodine atom. On the basis of theoretical calculations, Kirshenboim and Kozuch³⁵ have suggested that the split σ holes should be situated in the plane of the three substituents of the hypervalent atom and that halogen and covalent bonds should be coplanar. Fig. 3 shows that the C_aryl–I⋯O interaction in 1 closely matches this expectation, with the next oxygen neighbour O1′ only 0.47 Å out of the least-squares plane through the heavy halogen I1 and its three covalently bonded partners C1, O1 and C10.Open in a separate windowFig. 2Deformation density for the pair of neighbouring molecules in 1; the dashed blue and red arrows indicate regions of opposite charge. (Contour interval 0.10e Å⁻³; blue lines positive, red lines negative, green lines zero contours, symmetry operator 1 − x, 1 − y, 1 − z).Open in a separate windowFig. 3A molecule of 1, shown [platon] along O1⋯C1, and its halogen-bonded neighbour O1ⁱ. Symmetry operator 1 − x, 1 − y, 1 − z.The Laplacian, the scalar derivative of the gradient vector field of the electron density, emphasizes local charge accumulations and depletions and it allows to assess the character of intra- and inter-molecular interactions. A detailed analysis of all bonds in 1 according to Bader''s Atoms In Molecules theory⁴² is provided in the ESI.^‡ We here only mention that the electron density in the bond critical point (bcp) of the short intermolecular I⋯O contact amounts to 0.102(5)e Å⁻³; we are not aware of charge density studies on λ3-iodanes, but both the electron density and its small positive Laplacian match values experimentally observed for halogen bonds involving O and terminal I in the same distance range.⁴³The crystal structure of 1 necessarily implies additional contacts beyond the short halogen bond shown in Fig. 1 and ​and2.2. The shortest among these secondary interactions is depicted in Fig. 4: it involved a non-classical C–H⋯F contact with a H⋯F distance of 2.55 Å.Open in a separate windowFig. 4C–H⋯F contact in 1; additional information has been compiled in the ESI.^‡ Symmetry operators i = 1 − x, 1 − y, 1 − z; ii = 1 − x, 1 − y, −z.The topological analysis of the experimental charge density reveals that this non-classical C–H⋯F hydrogen bond and all other secondary contacts are only associated with very small electron densities in the bcps. Table S8 in the ESI^‡ provides a summary of this analysis and confirms that the I⋯O halogen bond discussed in Fig. 1 and ​and22 represents by far the most relevant intermolecular interaction.The relevance of this halogen bond extends beyond the crystal structure of 1: Insight into the spatial disposition of electrophilic and nucleophilic regions and hence into the expected reactivity of a molecule may be gained from another electron-density derived property, the electrostatic potential (ESP). The ESP for the pair of interacting molecules in 1 is depicted in Fig. 5.Open in a separate windowFig. 5Electrostatic potential for a pair of molecules in 1 mapped on an electron density isosurface (ρ = 0.5e Å⁻³; program MoleCoolQt^44,45). Fig. 5 underlines the complementary electrostatic interactions between the positively charged iodine and the negatively charged oxygen atoms. One can easily imagine to “replace” the inversion-related partner molecule in crystalline 1 by an incoming nucleophile.The ESP tentatively obtained for a single molecule in the structure of 1 did not differ significantly from that derived for the inversion-related pair (Fig. 5), and even the results from theoretical calculations in the gas phase for an isolated molecule²⁰ are in good qualitative agreement with our ESP derived from the crystal structure. In the absence of very short contacts, polarization by neighbouring molecules only has a minor influence on the ESP. The experimentally observed electron density matches the proven reactivity for the title compound, and we consider it rewarding to extend our charge density studies on related hypervalent reagents.     

Retracted Article: Facile preparation of bithiazole-based material for inkjet printed light-emitting electrochemical cell

Light-emitting electrochemical cell of bithiazole-based material was fabricated by solution processing rendered high external quantum efficiency over 12.8% and luminance of 1.8 10⁴ cd m⁻².

Light-emitting electrochemical cell of bithiazole-based material was fabricated by solution processing rendered high external quantum efficiency over 12.8% and luminance of 1.8 10⁴ cd m^−2.

It is well known that inkjet printing works as precise and versatile patterning method for printed electronics.^1,2 As for its advantages, it is already being exploited widespread for printing electronics.^3,4 Those merits are easily processed from solutions and conveniently used for air-stable electrodes.^5,6Light-emitting electrochemical cells (LECs) have emerged as an active layer,^7,8 arousing tremendous attention over the years.^9–11 Nevertheless, LECs are simpler than organic light-emitting diodes (OLEDs).^12,13 Due to its single layer architecture, low fabrication price and operating voltages, LECs are considered as a promising, next-generation, emissive thin-film technology.^14–16The most efficient device used to date for LECs are biscyclometalated iridium(iii) (Ir) complexes, because they have highly efficient and stable devices spanning the whole visible range.^17–19 However, avoiding the use of Ir is strongly desired because of its high cost and limited supply.^20–22 Till now, thiazole has worked as active component in a LECs system with a long-lived charge-separation molecule, without additional ions in its active layer.^23–26 As for its advantages, it can reduce recombination of charge carriers and facilitate carrier transfer.^27–29 More and more importance has been attached to thiazole compounds, especially bithiazole-based ones.^30–33 Therefore, these have aroused interest in the syntheses of bithiazoles.^34–36Based on our previous research,^37–41 the use of bithiazole ligands already explored by our group for photocatalytic technology has the advantage of an easy transformation of neutral complexes into charged ones by substitution on the N-atom of the thiazole moiety.^42,43 Furthermore, we demonstrate the fabrication of LEC devices by a combination of inkjet printing and spin coating, on A4 paper substrates for low cost, disposable and flexible conductive pattern.^44,45 Their corresponding material characteristics were closely investigated, a detailed report of the material properties of the resulting coatings, and an envisaged proof of concept application are disclosed in this paper. These fully printed devices demonstrate the potential upscaling of the fabrication of optoelectronic devices.Herein we report the design for a range of bithiazole derivatives 1a–1c (Fig. 1, their synthesis is shown in Scheme S1^†), and explore their properties. First of all, the UV-visible diffuse-reflectance (UV-vis DRS) spectra of those specimens at room temperature are displayed in Fig. 2 and the data are collected in Table S1.^† This enhancement was ascribed to the increase of aromatic rings, which has an intense absorption in the visible-light region. And their bandgap energies (E_g) are between 2.97–3.01 eV (Table S1^†), and are estimated from these absorption spectra according to the Kubelka–Munk method. Expanding the conjugated system and electron density with these donor groups, it can lead to a larger bathochromic shift of the absorption maximum.^46,47Open in a separate windowFig. 1Chemical structures of compounds 1a–1c described in this work.Open in a separate windowFig. 2UV-vis DRS spectra of 1a–1c.All of the three compounds are photoluminescent at room temperature, the relevant fluorescence peak maximum ranges from 360 to 398 nm (Fig. 3). They emit blue light when they are being excited. In agreement with Fig. 3, the presence of electron-releasing groups would shift the emission maximum. Among them, the most electron-donating carbazole unit would give the most red-shifted peak at 398 nm for 1c (Table S1^†). The PL quantum yield (ϕ_PL) studies show that both 1a and 1b are as high as 62 and 78%, while another one is 85% (Table S1^†). The data for their fluorescent quantum yields largely depends on interaction effect with molecules 1a–1c in the crystal packing. In this context, π–π intermolecular interactions can inhibit the fluorescence.⁴⁸Open in a separate windowFig. 3Typical PL spectra of 1a–1c.It may indicate that enlarging the conjugation length and electron density with these donor groups plays an important role in increasing the ϕ_PL.⁴⁹ Moreover, those with high ϕ_PL may be suitable for application as efficient light-emitting material in LECs.⁵⁰In addition, time-resolved measurements of the donor lifetime (τ) in 1a–1c were carried out, and their corresponding values are given in Table S1.^† The bithiazole derivatives 1a–1c showed long-lived singlet fluorescence lifetimes (τ_F), ranging between 1.04 and 9.54 ns (Table S1^†). This was on average more than double the fluorescence lifetime of the bithiazole starting material.⁵¹ These three samples possess relatively high decay time, as a result of their inhomogeneity.⁵² Compound 1c exhibited the longest fluorescence lifetime decay τ_F = 9.54 ns. The sensitivity of the emission to the polarity of the solvent is beneficial for an intramolecular charge transfer (ICT)-like emission.⁵³ This difference probably accounts for the high concentration of donor units in the bithiazole backbone, low rates of intersystem crossing to reactive triplet states.^48,54Consequently, the composite 1c was the best performing LEC and chosen for the below test. The EL spectra obtained for both devices were almost identical, with a main peak at 498 nm and other peak at 504 nm wavelength as illustrated in Fig. 4a. It may account for trapping, cavity, and self-absorption effects from within the LEC device 1c multilayer-structure. The spin-coated emission is quantified by the commission Internationale de L’Eclairage (CIE) coordinates of (0.28, 0.42), and a colour rendering index (CRI) of 65 (Table S2^†). While inkjet-printed light emission with CIE coordinates of (0.34, 0.43) and a CRI value of 83 was achieved for device 1c (Table S2^†). It exhibits good colour rendering indices (CRI > 70), this device exhibited a warm-white appearance, and the colour rendering is considered sufficient for indoor lighting applications.Open in a separate windowFig. 4Comparison of device characteristics with spin-cast and inkjet printer emitting layer for 1c: (a) electroluminescent spectra, (b) luminance vs. voltage, (c) current density vs. voltage, (d) efficiency vs. luminance behaviour.The time-dependent brightness and current density under constant biases of 2.9–3.3 V for device 1c are shown in Fig. 4b and c. Interestingly, the device with the inkjet-printed emitting layer (EML) produced a light output of around 3600 cd m⁻², whereas 4600 cd m⁻² was achieved with the spin-coated EML. In other words, the device with the inkjet printed EML obtained about 78.3% of brightness compared with the reference device. The differences between the two devices regarding current efficiency (J) and power efficiency (PE) were rather closed, as listed in the Table S2.^† A luminous efficiency much larger than 10 cd A⁻¹ was achieved for the inkjet-printed EML, which tended to be 73.9%, and is similar to the spin-coated emitting layer.The performance gap between the devices (Fig. 4d) can be attributed to differences in the height and surface roughness of the emitting layer.⁵⁵ Lateral sizing histograms (Fig. S11^†) show that the spin-coated EML possessed a thickness of 35 nm and a very smooth surface. The inferior performance of the inkjet-printed EML is caused by a less homogeneous surface morphology and an overall fatter layer.⁵⁶ The depth of the inkjet-printed EML ranged from 25 nm (pixel centre) to 35 nm (pixel edges). As a consequence, it is an inkjet deposition process and the related evaporation dynamics reduces the light output and efficiency, but also postpones the stability of the device in the system.^10,57We then shifted our attention to the turn-on kinetics, efficiency and long-term stability of the LEC device for 1c; the typical evolution of current density and light emission is presented in Fig. 5a and b, showing a slow turn-on followed by a progressive decay over time.Open in a separate windowFig. 5(a) Current density (closed symbols) and brightness (open symbols) versus time at 3 V for a device with the representative sample 1c; (b) EQE versus time at an applied voltage of 3 V.The build-up of the light output is synchronous with that of the current density. This time-delayed response is one of the striking features of the operation of an electrochemical cell and reflects the mechanism of device operation.²² The champion device in this set exhibited a peak power efficiency (PE) of 17.4 lm W⁻¹ at a luminance of 18 000 cd m⁻². Meanwhile, the current density began to decrease, possibly due to the electrochemical oxidation or electro corrosion that occurred on component 1c through accumulated electroinduced holes, and then it kept up a durative datum.⁵⁸ Apparently it exhibited outstanding long-term operation stability beyond 40 h (Fig. 5b).The time-dependent external quantum efficiency (EQE) of LEC for the representative substrate 1c are shown in Fig. 5b. It also exhibited similar temporal tendency in device efficiency. When a bias was applied on the LECs, the EQE quickly increased since balanced carrier injection was achieved by the formation of the doped layers.⁵⁹ After attaining the crest value, the device current was still rising while the EQE reduced little by little. It implied that both growing the doped layers and weakening of the EQE was resulting from exciton quenching near the bithiazlole core in persistently extended doped layers.⁶⁰ Doping-induced self-absorption was rather adaptable to the temporal roll-off in device efficiency. This configuration shows the best performance (EQE = 12.8%) compared to those devices prepared with the single compounds, which is given in Table S3.^† The reason may be that the steady-state recombination zone in 1c device was close to the central active layer.⁶¹ Besides it contains fluorenes on its side chains, constructing plane structure, benefiting from good electron injection abilities, leading to enhancing the EQE itself.⁶²The fabrication of inkjet-printed bithiazole interdigitated electrode (IDE) is illustrated in Fig. 6. All the prepared varieties of bithiazole-based ink have been found to be highly stable with nil or miniscule precipitation in over 180 days being stored on the shelf (Fig. 6a). After HCl treatment of the paper substrate, the prepared inks have filled within ink cartridges of a low-cost desktop printer Canon iP1188 (Fig. 6b). Fig. 6c shows the photograph of inkjet-printed conductive patterns.Open in a separate windowFig. 6(a) The representative ink based on sample 1c was stable for 180 days; (b) electrode printing using Canon iP1188 printer; (c) scale showing size of printed electrodes; (d) interdigitated electrode (inset shows small size printed pattern).In addition, the most attractive prospect of the bilayer device structure at this stage is the possibility for patterned emission for the creation of a static display. Fig. 7 presents a photograph of a small portion of a larger static display, with a resolution of 170 PPI, which repeatedly exhibits a message in the form of the word “LEC”. As shown in Fig. 7, the pixel array produced are fairly luminous. The EL spectra were collected from each pixel on the substrate, the emission peak wavelength was about 510 nm and the full width at half maximum was about 170 nm. The low variation in emission intensity in the different pixels implies a small variation in thickness of the solution-coated layers. More specifically, if we assume a minimum diameter of 20 μm for an inkjetted electrolyte droplet, and a smallest inter-droplet distance of 10 μm, we attain a pitch of 30 μm, which corresponds to a high display resolution of 850 PPI. Finally, we draw attention to the herein presented static-display LEC that comprises solely air-stabile materials, and that we routinely fabricate the bilayer stack under ambient atmosphere.Open in a separate windowFig. 7(a) The patterned light emission from a bilayer LEC, with the emission pattern defined by the selected positions of the ink jetted electrolyte droplets. (b) The droplet diameter and pitch were 50 and 150 μm, respectively, and the device was driven at V = 3 V. The scale bar measures 300 μm.     

Characterization of biosurfactant lipopeptide and its performance evaluation for oil-spill remediation

Biosurfactant lipopeptide is a promising dispersant over varieties of chemical ones in oil-spill remediation. The toxicity, biodegradability and performance of the biosurfactant lipopeptide are studied in this paper.

Biosurfactant lipopeptide is a promising dispersant over varieties of chemical ones in oil-spill remediation.

Dispersants were globally applied to physico-chemically enhance the dispersion of oil in water and were assumed to stimulate oil biodegradation by indigenous microorganisms and to reduce the environmental impact of oil spills.^1,2 Since the 1960s,^3,4 chemical dispersants have been applied as an emergency response to oil spills in marine ecosystems,⁵ and have showed effectiveness at removing oil slicks from the coast.^3,6,7 However, most of the chemically synthesized dispersants are inherently toxic to various aquatic species and hardly biodegradable in the natural environment.^2,8 The application of chemical dispersants in the 2010 Gulf of Mexico oil spill also raised concerns regarding the toxicity and the potential environmental impact,^9,10 and caused a debate about the effectiveness of chemical dispersants on the rates of oil biodegradation.¹¹ Biosurfactants are promising dispersants in oil-spill remediation, owning to their environmentally friendly and biodegradable properties.¹² Chemical surfactants could be replaced with biosurfactants and this change would diminish the environmental impact of traditional dispersants.^8,13,14 Lipopeptide produced by microorganisms is one of the representative biosurfactants and has showed great potential applications in food,¹⁵ medicine,¹⁶ microbial enhanced oil recovery,¹⁷ and other fields.¹⁸ Nevertheless, the knowledge about the application of biosurfactant lipopeptide in marine oil-spill remediation is still limited.In the present work, the dispersion effectiveness, aquatic toxicity, biodegradability and environmental compatibility of the biosurfactant lipopeptide were determined using recognized standardized methods,^19–23 and the biosurfactant lipopeptide used as a bio-dispersant for marine oil-spill remediation were studied, which is, to the best of our knowledge, the first report about biosurfactant lipopeptide used in oil-spill remediation.The lipopeptide samples were isolated from cell-free broth of B. subtilis HSO121 at our laboratory.²⁴ The typical chemical structure of the lipopeptide used in the study was shown in Fig. 1 and its critical micelle concentration (CMC) was 8.69 × 10⁻⁵ mol L⁻¹.Open in a separate windowFig. 1Typical chemical structure of lipopeptides (a) and the surface tensions of lipopeptides respect to concentrations (b).Dispersion effectiveness (DE) of lipopeptides was examined at different surfactant-to-oil ratios (SORs), temperatures, pH values, and salinities. It indicated in Fig. 2 that DE of lipopeptides reached 70.23% at SORs of 1 : 10 (w/w) at 25 °C, pH 7 and the present of 3% NaCl (w/v). It should be noticed that the DE of lipopeptides was almost kept when SORs dropped to 1 : 250 w/w. The increase in DE with increasing SORs can be attributed to the generation of emulsions with smaller droplets and lower rising velocity.² Sharp drop off in DE was observed for lipopeptides when SORs below 1 : 500 (w/w), and DE value was 36.45% at an extreme SORs of 1 : 1250 (w/w). It had been reported that the abrupt decline for 80 : 20 lecithin : Tween 80 (w/w) surfactant happened when SORs below 1 : 100 v/v, from 77% (SORs 1 : 100 v/v) to 15% (SORs 1 : 200 v/v),²⁵ indicating a lower SOR in lipopeptides usage could reach its maximum effectiveness. Lipopeptides exhibited >70% DE values with temperatures ranged from 15 °C to 25 °C, and an increasing DE values when pH values raised, the largest DE was 77.45% at pH 11. DE of lipopeptides increased from 56.12% to 71.14% with increase in salinity. Higher DE at higher salinity was observed for anionic biosurfactants, which can be attributed to the electrostatic repulsion between polar head groups reduced by ions, and a close-packed arrangement of surfactant molecules at the oil–water interface were formed.²Open in a separate windowFig. 2The dispersion effectiveness (DE) of lipopeptides under different SORs (), temperatures (), pH values () and salinities ().Mortalities of zebrafish under different concentrations of different surfactants were shown in Fig. 3. It was evident that the toxicity of lipopeptides was far less than those of sodium dodecyl sulfate (SDS) and 3-(N,N-dimethyl palmityl ammonio) propane sulfonate (Betaine). The 24 h median lethal concentration (LC₅₀) values were calculated and showed in 26 in which an 96 h LC₅₀ of 1.9 mg L⁻¹ for Cyprinodon variegatus was reported. Low toxicities of lipopeptides on whiteleg shrimp and copepods were also evaluated that the 96 h LC₅₀ of lipopeptides from Bacillus sp. GY19 were 1050 mg L⁻¹ and 1174 mg L⁻¹, respectively.²⁷Open in a separate windowFig. 3Mortality of zebrafish (M_z) after a 24 h exposure to Betaine, SDS or lipopeptides.Ecotoxicity of tested surfactants to the zebrafish

Colour-tunable ultralong organic phosphorescence upon temperature stimulus

A new class of single-component molecular crystal with colour-tunable ultralong organic phosphorescence (UOP) was designed and synthesized through alkyl chain engineering. Forming a more rigid environment at 77 K, the colour-tunable UOP from yellow-white to blue-green is achieved through dual-emission of crystal and amorphous states.

A new class of single-component molecular crystal with colour-tunable ultralong organic phosphorescence (UOP) was designed and synthesized through alkyl chain engineering.

Ultralong phosphorescence, a kind of phosphorescence that can be observed by the naked eye after removing the excitation source, has received great attention in the fields of sensing,¹ displays,² imaging,³ anti-counterfeiting⁴ and so on during the past years. Unfortunately, it is limited to inorganic materials because of the weak spin–orbit coupling (SOC) and strong non-radiative transition of pure organic materials.⁵ Compared with inorganic materials, however, organic materials have some excellent merits, such as inexpensive cost, relative safety to the environment, and soft preparation conditions.⁶ The realization of UOP becomes very significant. As mentioned above, UOP can be achieved by promoting intersystem crossing (ISC) through enhancing SOC and suppressing non-radiative transitions. In view of these factors, various strategies such as polymerization,⁷ H-aggregation,⁸ crystallization,⁹ host–guest doping,¹⁰ and freezing conditions¹¹ have been explored to achieve UOP with the unremitting efforts of scientific researchers.Intelligent-response organic luminescent materials can change their luminescent properties such as colour, lifetime, intensity, etc. after being stimulated by the external factor, such as mechanical forces, temperature, pH, light, solvent, etc., which have caught great attraction. The sensitivity of luminescent molecule to excitation wavelength, temperature or oxygen can be applied in sensors, optical recording and so on.^12–14However, the luminescence of these materials with intelligent-response are mostly limited to fluorescence or room temperature phosphorescence (RTP) with relatively short lifetimes.^15–18 Few samples display persistent luminescent feature.¹⁹ Most organic compounds can only tune their afterglow properties by changing molecular side groups or multi-component doping.^20–23 Therefore, the development of single component UOP materials with intelligent response remains a challenge. Inspired by the alkyl-chain engineering²⁴ and freezing conditions, herein we speculate that temperature response UOP might be induced by controlling the activity of the alkyl chain to regulate non-radiative transition rate. By means of reducing the temperature to restrict the molecular motions at amorphous state, colour-tunable UOP with temperature-response can be realized by dual-emission of molecules at both amorphous and crystalline states.In our previous study, MCzT crystals showed yellow UOP at RT.²⁵ The crystals showed the same UOP at 77 K with that at RT (Fig. 1a). Here, 9-(2-((4,6-dimethoxy-1,3,5-triazin-2-yl)oxy)ethyl)-9H-carbazole (MTOD) was designed and via alkyl chain attaching carbazole with a triazine core. The target molecule was characterized by ¹H NMR and ¹³C NMR (Fig. S1–S3^†). Its melting point reaches 130 °C. (Fig. S4^†) MTOD achieved a lifetime of up to 860 ms under ambient conditions. Surprisingly, the UOP changed from yellow-white to blue-green after the removal of the UV-lamp for several seconds at 77 K (Fig. 1b), demonstrating colour-tunable property of UOP with a low temperature stimulus.Open in a separate windowFig. 1Molecular structures and UOP photographs of MCzT (a) and MTOD (b).In order to explore the reasons for the colour-tunable UOP of MTOD at low temperature. The photophysical properties of MTOD in the crystal state were first investigated under ambient conditions. As shown in Fig. 2a, the photoluminescence (PL) spectrum of MTOD shows two main emission peaks at 375 and 413 nm and a shoulder at 435 nm. From the lifetime decay profiles (Fig. S5a^†), it was confirmed that they were all assigned to the fluorescence. Notably, the crystals of MTOD presented yellow afterglow after turning off the UV lamp. From the delayed phosphorescence spectrum, the main emission of MTOD was located at 414, 556 and 600 nm with lifetimes of 681.91, 860.56 and 860.59 ms, respectively (Fig. 2b and S5b^†). Among these, the emission around 414 nm is assigned to triplet–triplet annihilation (TTA) fluorescence originating larger π–π overlaps of carbazole groups from the crystal data (Fig. S6^†).²⁶ Remaining two emission peaks are attributed to UOP emission. From the phosphorescence excitation-emission spectra of MTOD, UOP can be efficiently excited from 260 to 380 nm, with the optimal excitation at 360 nm (Fig. S7^†).Open in a separate windowFig. 2Photophysical properties of MTOD at room temperature and at 77 K. (a) Steady-state photoluminescence (PL, blue dashed line) and phosphorescence (red solid line) spectra at RT and 77 K. Inset: photographs taken after removing excitation. (b) Time-resolved phosphorescence decay of the emission bands at 556 and 600 nm at room temperature, respectively. (c) Time-resolved phosphorescence decay of the emission bands at 478, 564 and 612 nm at 77 K, respectively. (d) PL (blue dashed line) and phosphorescence (red solid line) spectra at molten state.Subsequently, we measured the PL and phosphorescence spectra of MTOD at 77 K (Fig. 2a). The steady-state PL spectrum showed four peaks at 361, 376, 410 and 436 nm, with little change compared with its corresponding spectrum at RT. However, a new phosphorescence peak appears at about 480 nm with an intense emission than others, which displays an ultralong lifetime of 2.5 s. Obviously, the new emission peak plays an indispensable role in the colour-changed UOP at 77 K. The yellowish-white UOP observed by naked eyes at 77 K is generated by the combination of three phosphorescence peaks. However, as time goes by, only the blue-green afterglow at about 480 nm due to the shorter lifetime of long-wavelength phosphorescence can be observed.To find out the origin of this new peak at 480 nm, the PL and phosphorescence spectra of MTOD at molten state were measured as amorphous emission. As shown in Fig. 2d, the PL peak is located at 380 nm and the phosphorescence spectrum shows a broad band with a main peak at 484 nm. It is suggested that the new phosphorescence emission peak at 77 K may be attributed to amorphous state. Taken together, we deduce that the colour-tunable property of the crystal is possibly due to the presence of an amorphous state at low temperature.The X-ray single crystal diffraction of MTOD crystal was taken to explore the mechanism of UOP at room temperature. Abundant intermolecular and intramolecular interactions (Fig. 3a, S6, S8 and S9a^†) in the crystals strongly restrict the torsional molecular configuration. The dihedral angle between the triazine and carbazole groups is about 75° (Fig. S10^†). In the crystal of MTOD, the single molecule is limited by multiple intermolecular interactions, including C–H⋯N (2.681 Å), π-H⋯π (2.791, 2.876 Å), π-H⋯N (2.703, 2.711 Å) (Table S3^†). The rich intermolecular interactions are beneficial to limit molecular motions to suppress non-radiative transitions of excited molecules, leading to UOP. However, the amorphous molecules around the crystals with weak restriction displayed negligible phosphorescence at room temperature due to the strong motions of alkyl chains.Open in a separate windowFig. 3Intermolecular interactions (a) at room temperature and (b) at 100 K.Comparatively, the single crystal of MTOD molecule at 100 K was measured in order to explore the colour-changing mechanism of UOP at low temperature (Fig. 3b and S9b^†). By comparison, MTOD crystals exhibit more intermolecular interactions at 100 K and the distance become shorter. Molecular conformation of MTOD changed slightly, the dihedral angle between triazine and carbazole changed from 74.95° to 75.32° (Fig. S10^†). These increased interactions can constrain the molecules more effectively and the stronger restriction of alkyl chain and carbazole will further suppress non-radiative transitions, resulting in the much longer phosphorescence lifetime of over 1.0 s at low temperature. Compared with the molecules in the crystalline state, freezing condition can provide a more rigid environment to minimize the movement of the alkyl chain, greatly reducing the non-radiative transition rate at amorphous state, resulting in the lifetime of short wavelength phosphorescence at 478 nm up to 2.5 s.According to the above results, the photophysical process of colour-tunable phosphorescence can be described by Jablonski diagram as shown in Fig. 4. Upon photoexcitation, both electrons in amorphous and crystalline molecules transforms to lowest singlet states (S₁). Then, the electrons in S₁ would further transform to the lowest triplet (T₁) through ISC. At room temperature, amorphous molecules show strong molecular motions to facilitate the non-radiative transitions. However, crystalline molecules due to closely arrangement can exhibit phosphorescence through radiative decay. At 77 K, both excitons in amorphous and crystal states are dominated by radiative transitions, leading to colour-tunable UOP.Open in a separate windowFig. 4(a) Jablonski diagram of the relevant photophysical processes illustrating amorphous and crystalline UOP process at room temperature (top) and 77 K (bottom). (b) Phosphorescence spectra of MTOD at different temperature and (c) corresponding coordinates in CIE.In view of the interesting luminescent phenomenon, we have investigated a series of phosphorescent spectra of MTOD crystals at different temperatures ranged from 183 to 273 K. As shown in Fig. 4b, as the temperature increases, the phosphorescence intensity of the amorphous molecules gradually decreases. The colour variations of the MTOD crystals in response to the environmental temperatures are shown in the Commission International de l’Eclairage (CIE) coordinate diagram (Fig. 4c). As the temperature was gradually changed from 183 to 273 K, the UOP changed from green to yellow with good linearity of the CIE coordinates. This demonstrated that MTOD crystals may have potential in low temperature sensing.In conclusion, we synthesized a colour-tunable single-component UOP compound through alkyl chain engineering. Combined the spectral and single crystal analyses, it is indicated that colour-tunable UOP comes from dual-emission of molecules at amorphous and crystalline states. Low temperature provides better rigid effect on UOP of amorphous molecules than crystals, resulting in the UOP colour changed from yellow-white to blue-green. More interestingly, red-shifted UOP of MTOD crystals with the increase of temperature can be achieved, demonstrating its potential for temperature sensing. This study will provide a platform for the design of single-component UOP molecules with tunable colour emission and broadens its application field.     

Complement activation by gold nanoparticles passivated with polyelectrolyte ligands

Gold nanoparticles passivated by polyelectrolyte ligands are widely used to confer stability and biofunctionality. While nanoparticles and polyelectrolytes have been reported as activators, their ability to activate the complement system as hybrid polyelectrolyte-coated nanoparticles is poorly characterized. Here, we found that gold nanoparticles passivated by common polyelectrolytes activated the system differently. The surface area of AuNPs appeared to be a major determinant of complement activation level as it determined the amount of adsorbed polyelectrolytes. Although a moderate negative correlation between AuNP surface hydrophilicity and their activation level was observed, the surface charge and functional group of polyelectrolyte ligands also influenced the final complement activation level.

We reported that the surface area and hydrophilicity of polyelectrolyte-coated gold nanoparticles influence their complement activation, a biological response not well understood to date.

Nanomaterials may elicit various biological responses upon contact with blood, of which activation of the complement system in innate immunity is one of the earliest.^1–3 The complement system is a collection of over 40 soluble and membrane-bound proteins, which acts in any of three distinct enzymatic cascades: classical, lectin, and alternative leading to the formation of a C3 convertase complex, and its accompanying range of biological responses, including inflammation, opsonization and cytolysis.^2,4While these responses could lead to undesirable physiological responses from over-activation and rapid clearance of nanomaterials from circulation, the intricate link between complement activation and adaptive immunity^5–7 also presents opportunities for exploitation in immune-related applications such as vaccines development. Therefore, complement activation by nanomaterials in biomedical applications has attracted great attention recently.^3,8–10We previously reported complement activation by gold nanoparticles (AuNPs) of different shapes in their as-synthesized citrate and CTAB coatings.¹¹ Polyelectrolyte ligands are also widely used in the preparation of AuNPs not only to stabilize AuNPs against aggregation, but to also enhance their solubility and confer additional surface functionalities.^12–14 These polyelectrolytes with different functional groups have been reported as complement activators in both their particulate and planar surface-immobilized forms.^15–21 However, the ability of polymer-passivated AuNPs to activate the complement system and the underlying mechanism remain poorly understood, although our previous study demonstrated that passivating the surface of AuNPs by poly(ethylene glycol) (PEG) modulated the activation level.¹¹Herein, we stabilized different shapes of AuNPs with different polyelectrolytes and examined their levels of complement activation and underlying mechanism. This would provide rational guidelines on the use of polyelectrolytes to modulate complement activation. All polyelectrolytes used in this study are hydrophilic and widely used as delivery platforms^5,22 and surface passivating ligands of nanomaterials²³ (Scheme 1).Open in a separate windowScheme 1Schematic illustration of gold nanoparticles (AuNPs) core, polyelectrolytes and methods used in this study. AuNPs with spherical shape of 20 nm (Au20) and 40 nm (Au40) as well as rod-shape (AuNR) were used as AuNP cores. These AuNPs were passivated with various polyelectrolyte ligands, examined for their hydrophilicities and levels of complement activation.Spherical AuNPs of two diameters, 20 nm (Au20) and 40 nm (Au40), were synthesized by well-known citrate reduction method.²⁴ AuNPs of rod-like shape (AuNR) were synthesized by hexadecyltrimethylammonium bromide (CTAB)-mediated method²⁵ with the CTAB ligands subsequently replaced by citrate using previously established protocol.²⁶ All AuNPs were then passivated by different polyelectrolytes following previously established layer-by-layer protocols (see Experimental section, ESI^†). With this library of AuNPs, we sought to examine the effects of size and shape of AuNP core as well as polyelectrolyte shell on the level of complement activation.The TEM images showed that Au20 and Au40 were spherical and homogenous while AuNR was rod-shaped with dimensions of approximately 40 × 10 nm (Fig. 1a–c). Hydrodynamic diameters, D_h, (Fig. 1d) were consistent with sizes of 20.2, 41.8, and 10.6 × 40.2 nm obtained from TEM images for Au20, Au40, and AuNR respectively (Fig. S1b–e, ESI^†). The UV-Vis absorption spectra showed surface plasmon resonance (SPR) peaks of 523 nm and 530 nm for Au20 and Au40, respectively while AuNR had transverse peak of 509 nm and longitudinal peak of 800 nm (Fig. S1a, ESI^†).^27,28 All citrate-capped Au20, Au40 and AuNRs had similar zeta potentials of −30 mV, which became nearly neutral after passivated with poly(vinyl alcohol) (ζ_AuNP-PVA ≈ −5 mV) and polyamidoamine (ζ_AuNP-PAMAM ≈ −10 mV) (Fig. 1e). In contrast, surface passivation with poly(acrylic acid) (AuNP-PAA), poly(styrenesulfonate) (AuNP-PSS), and heparin (AuNP-Heparin) conferred AuNPs a more negative zeta potential of ≈−40 mV (Fig. 1e), while coating with poly(ethyleneimine) (AuNP-PEI) conferred AuNPs a positive surface charge of ≈+40 mV. The presence of polyelectrolytes on AuNPs was further confirmed by the increase in D_h of polyelectrolyte-passivated AuNPs (Fig. 1d).Open in a separate windowFig. 1Physical properties of library of AuNPs. TEM images of (a) citrate-capped Au20, (b) Au40, and (c) AuNR. (d) Hydrodynamic diameter, D_h, and (e) zeta potential, ζ, of citrate-capped AuNPs and polyelectrolyte-passivated AuNPs. Each data point represents mean ± standard deviation (SD) of triplicate experiments. Scale bar in the TEM images represents 50 nm.When these polyelectrolyte-passivated AuNPs were incubated in normal human serum, the generation of SC5b-9 as an endpoint biomarker showed complement activation regardless of the activation pathway.^3,4,8 Here, elevated levels of SC5b-9 were detected in all AuNPs-treated sera (Fig. 2), indicating activation of the complement system. Prior to surface passivation by polyelectrolytes, we observed an expected complement activation by AuNP-citrate, although the level was significantly lower than our positive control zymosan (a well-known complement activator derived from the wall of yeast cell). Also, Au40-citrate induced more SC5b-9 than Au20-citrate and AuNR-citrate (Fig. 2).Open in a separate windowFig. 2Detection of endpoint product of complement activation, SC5b-9, using ELISA kit. 1× PBS and zymosan (10 mg ml⁻¹) were used as negative (−) and positive (+) controls, respectively. Each data point represents the mean ± standard deviation of triplicate experiments.The level of complement activation was dependent on both the AuNP core and polyelectrolyte ligand. Amongst the polyelectrolytes, we observed the highest level of complement activation from PEI, comparable or even higher than zymosan (Fig. 2). This agreed with previously published results where positively charged polymers carrying primary amino groups were shown to interact strongly with complement proteins to activate the complement system.^18,21Between the three AuNP cores, Au40-PEI had the highest level of complement activation ([SC5b-9] = 1.80 μg ml⁻¹), followed by Au20-PEI ([SC5b-9] = 1.29 μg ml⁻¹) and AuNR-PEI ([SC5b-9] = 1.16 μg ml⁻¹), which had comparable levels of complement activation (Fig. 2). The same trend was true not only for AuNPs-PEI but also other polyelectrolyte-passivated AuNPs. While complement activation by nanomaterials have been shown to depend on their sizes and shapes,^8,29 the differences observed here were more likely attributed to the amount of PEI adsorbed on the surface of AuNPs, which was in turn dictated by their surface area, since PEI by itself has been shown to activate the complement system in concentration-dependent manner.¹⁸ Here, Au20 and AuNR had comparable surface areas (1256 and 1413 nm², respectively) and hence similar levels of complement activation, while Au40 had the largest surface area (5024 nm²), thus accounting for the highest level of complement activation (Fig. 2).Unlike PEI, AuNPs passivated by both PVA and PAA induced the lowest levels of SC5b-9 (Fig. 2). While PVA is widely known as a biocompatible ligand on AuNRs,²³ its complement activation was not totally avoided probably due to its nucleophilic hydroxyl groups,^16,17 similar to PEI with nucleophilic amine groups. However, its complement activation level was much lower, and was likely due to its near neutral surface charge which did not promote interaction with many negatively charged complement proteins unlike the positively charged PEI.Similarly, the highly negative charge AuNP-PAA due to high density of carboxyl groups did not promote their interaction with negatively charged complement proteins, thus inducing an equally low level of complement activation as AuNP-PVA. Therefore, PAA is one of the most widely used water-soluble polyelectrolyte, superabsorbent polymer as well as food additive. Nonetheless, PAA conjugated to IgG has been found to specifically interact with positively charged C1q complement protein to activate the classical pathway.^30,31 Hence, AuNP-PAA has been found to promote inflammation via activation with fibrinogen.³² In this study, the AuNP-PAA could have activated the complement system via the classical pathway due to their interactions with C1q complement protein as reported.^30,31Owing to its nature as an anticoagulant, heparin has been reported to minimize complement activation.^33–35 However, we found that AuNP-heparin still activated the complement system although their level of complement activation was comparable to PVA and PAA, and much lower than PEI, PSS and PAMAM.Interestingly, despite the presence of nucleophilic amine groups on PAMAM similar to PEI, AuNP-PAMAM activated the complement system at much lower levels compared to AuNP-PEI. PAMAM dendrimers were known to be generation-dependent complement activators with stronger complement activation observed in higher generations.¹⁵ Here, we used PAMAM of generation 2.0 with aminoethanol surface and reasoned that coupling of amine with hydroxyl group helped to reduce activation level of AuNP-PAMAM. In fact, the activation level of AuNP-PAMAM was between that of AuNP-PVA with hydroxyl groups, and AuNP-PEI with amine groups. Furthermore, since primary amine groups adsorbed more C3b, a major component of complement proteins in serum, than secondary or tertiary amino groups,²⁰ the lack of primary amine group in PAMAM also explained its weaker complement activation than PEI which possesses a mixture of primary, secondary, and tertiary amine groups.The amount of SC5b-9 induced by AuNP-PSS was comparable to that of AuNP-PAMAM (Fig. 2). PSS is a widely used polyelectrolyte building block in layer-by-layer assembly,³⁶ and we used it as an intermediate ligand to prepare AuNR-citrate (Fig. S2, ESI^†). PSS by itself interacted with complement proteins of the classical pathway to activate the complement system.¹⁹ Our results not only confirmed complement activation by PSS passivation but also highlight the potential side effects of block-copolymer containing PSS commonly used as drug delivery platform in activating the complement system.Since the hydrophilicity of nanoparticles has been shown to modulate non-specific protein adsorption³⁷ and dictate immune response,³⁸ we further examined for possible correlation between the hydrophilicity of polyelectrolyte-passivated AuNPs and their level of complement activation. We measured relative hydrophilicity of polyelectrolyte-passivated AuNPs by dye absorption using a hydrophilic dye Nile Blue which interacted with a hydrophilic moiety (see Experimental section, ESI). On mixing the dye with AuNPs passivated with different polyelectrolyte ligands, we determined the partitioning quotient (PQ) as the ratio of dye bound on nanoparticles surface to the amount of free dye. In a plot of PQ versus surface area of nanoparticles, the slope of this linear regression line represented relative surface hydrophilicity.³⁹We observed different levels of hydrophilic dye adsorption on all polyelectrolyte-passivated AuNPs after 3 h incubation, indicating differences in their hydrophilicities (Fig. S8–10, ESI^†). AuNPs-PEI was the least hydrophilic (Fig. 3) as determined from the smallest slope of the linear regression line (Table S1, ESI^†), while AuNPs passivated with PVA, PAA, and heparin are amongst the most hydrophilic as given by the larger slope of the PQ vs. nanoparticle surface area plot (Fig. 3 and Table S1, ESI^†).Open in a separate windowFig. 3Negative correlation between surface hydrophilicity and complement activation by polyelectrolyte-passivated (a) Au20, (b) Au40 and (c) AuNR. X scale bar was plotted as ln of the value of relative hydrophilicity.We also observed a negative correlation between surface hydrophilicity and complement activation level across all AuNPs regardless of shape or size (Fig. 3). However, this correlation was only moderate with Pearson correlation coefficient, r = −0.2730, −0.4101, and −0.5489 for Au20, Au40 and AuNR, respectively (Fig. 3). Since Moyano et al. reported a positive correlation between nanoparticle surface hydrophobicity and their immune response previously,³⁸ the similarity in our observations suggested that the complement system could be a potential mediator between surface hydrophilicity/hydrophobicity and downstream immune response. Nonetheless, our results also demonstrated the complexity of complement activation by engineered nanomaterials, as it was not dependent solely on any one physical property such as shape, size, surface charge, surface functional group or surface hydrophilicity, but the interplay of these properties to influence the complement proteins adsorption.In summary, AuNPs passivated with different polyelectrolyte ligands activated the complement system at different levels, as characterized by the presence of endpoint product of complement activation, SC5b-9. The surface area of AuNPs appeared as a major determinant of complement activation level as it determined the amount of adsorbed polyelectrolytes. Although a moderate negative correlation between AuNPs surface hydrophilicity and their activation level was observed, the surface charge and functional group of polyelectrolyte ligands also influenced the final complement activation level. These findings provide new insights to rational selection and design guidelines for the use of polyelectrolytes to either suppress complement activation and downstream immune response for nanoparticulate drug delivery systems or to enhance complement activation and immune response for vaccine development.     

Mesoporous-silica-coated palladium-nanocubes as recyclable nanocatalyst in C–C-coupling reaction – a green approach

We report the straightforward design of a recyclable palladium-core–silica-shell nanocatalyst showing an excellent balance between sufficient stability and permeability. The overall process – design, catalysis and purification – is characterized by its sustainability and simplicity accompanied by a great recycling potential and ultra high yields in C–C-coupling reactions.

A green approach: in a single-step coating process a mesoporous silica shell was tailored onto palladium-nanocubes. Along with a PEG-matrix this core–shell-nanocatalyst could be recovered after C–C-coupling reactions and reused without any significant decrease in product yield.

In contrast to bulk materials, metal-nanocyrstals (NC) possess unique physical and chemical properties. Both, nano-scale and geometry can dictate their optical, electronic and catalytic behavior.^1–3 Consequently, nanomaterials have been implemented already in various fields like medicine,⁴ sensing,⁵ nano-electronics⁶ and organic synthesis.⁷ Smart strategies for a sustainable usage of limited resources such as precious metals and hydrocarbons are inevitable due to the consistently growing population and economy.^8–10 Generally, catalysis gives rise to novel and energy-saving synthetic routes. However, homogeneous catalysis is not widely used in industrial processes, due to the need of mostly toxic ligands and the costly purification along with a restricted reusability potential.^11–13 Heterogeneous catalysis based on the utilization of metal nanocrystals overcomes most of these limitations. Caused by its high surface-to-volume ratio, catalytic activities are drastically increased in comparison to bulk materials. However, the most common disadvantage in NC-based catalysis lies in the occurrence of aggregates during the reaction, which leads to a decrease of the catalytic active surface. Several studies were already presented in literature to delay that phenomenon using micelle-like- or core–shell-nanostructures as potential nanocatalytic systems.^14–20 However, these surfactants or shells are either potentially harmful for the environment or very step-inefficient to produce. Other approaches used the deposition of small NCs in a mesoporous support which offers a large active surface area.^21–24 In this context, it is crucial to find an adequate balance between permeability for small organic molecules and the overall stability of the nanocatalyst. Overcoming these obstacles can contribute to a sustainable supply of drugs and other organic substances.In the present work palladium-nanocubes (Pd-NCubes) were fabricated in aqueous solution using cetyltrimethyl-ammoniumbromide (CTAB) as surfactant. The procedure is adapted from a previously published study.^25,26 The respective transmission electron microscopy (TEM) image and the selected area electron diffraction (SAED) pattern of the as-obtained Pd-NCubes are depicted in Fig. S1.^† The SAED confirms the single-crystallinity of Pd-NCubes bound by {100}-facets. TE micrographs of Pd-NCubes revealed an average edge-length of (18 ± 2) nm (for histogram see Fig. S2^†). The formation of polyhedra and nanorods was found to be less than 1%.To the best of our knowledge, there is no procedure reported that showed the direct fabrication of a mesoporous silica (mSi) shell tailored on Pd-NCs. However, Matsuura et al. demonstrated a single-step coating approach of CTAB-capped gold-nanorods and CdSe/ZnS quantum dots obtaining a mesoporous silica shell.²⁷ The pores were determined to be 4 nm in width with 2 nm thick walls. Since the Pd-NCubes are covered by CTAB, already no surfactant exchange is necessary. Consequently, this procedure could be directly transferred to the as-obtained Pd-NCubes (∼10¹⁵ particles per L) of this study using tetraethyl orthosilicate (TEOS) as silica precursor in an alkaline solution. Here, CTAB serves as organic template for the formation of the mesoporous silica shell.TE micrographs of individual Pd-mSi-nanohybrids are depicted in Fig. 1 showing a spherical silica coating with a thickness of (17 ± 2) nm (for histogram see Fig. S3^†). The porosity is essential to ensure that vacant coordination sites on the palladium-core are present and accessible for catalysis. In contrast to other multistep approaches, pores are formed in situ with no additional etching step necessary.^28,29 This avoids the usage of harmful etching agents such as fluorides or ammonia.³⁰ The silica shell then served as platform for further surface modification using two different PEG-silanes (M_n = 5000 g mol⁻¹ and M_n = 20 000 g mol⁻¹). TE microscopy did not reveal any changes in the structure of the PEG functionalized Pd-mSi-nanohybrids opposed to the unfunctionalized nanocatalyst, since the contrast of polymer is too low (see Fig. S4^†). However, dynamic light scattering (DLS) measurements in diluted aqueous solutions proved an increased hydrodynamic radius with increasing molecular weight of the PEG-chain grafted onto the silica shell (see Fig. 2). These results provide evidence that only individual nanostructures are formed while no larger aggregates are present.Open in a separate windowFig. 1Exemplary TE micrographs of Pd-mSi-nanohybrids.Open in a separate windowFig. 2DLS results along the different stages of the hierarchal fabrication process of the nanocatalyst.The successful functionalization of the Pd-mSi-nanohybrid with PEG provides the dispersibility for the overall nanocatalyst in a PEG matrix. Due to its lack of toxicity and its simple recovery, caused by its melting point at ∼50 °C, PEG is considered as a “green” reaction medium.³¹ It has already been shown that PEG can act as suitable solvent for both homogeneous and heterogeneous catalysis.^32–34 Consequently, further experiments were performed using only the Pd-mSi-nanohybrid functionalized with PEG-silane having an average molecular weight of M_n = 5000 g mol⁻¹ (PEG-5k). For catalytic reactions, Pd-mSi-PEG-5k was dispersed in a PEG matrix (PEG-2000, M_n = 2000 g mol⁻¹) and charged into a Teflon centrifuge tube. Using only one tube for the reaction and the product separation avoids an additional transfer step and prevents any loss of the nanocatalyst between reaction cycles (see recycling Scheme 1). Here, the C–C-coupling between ethyl acrylate and p-iodoanisole served as model Heck-reaction to prove the catalytic activity of the designed catalyst (4.4 mol% overall Pd conc. equal to ca. 0.3 mol% surface-available Pd; conc. is determined by ICP-MS measurements, see Table S1^†). Sodium phosphate was used as base providing the largest product yield when compared to other bases, such as Na₂CO₃, K₂CO₃ and K₃PO₄. Once the catalysis was performed and the PEG-2000 was cooled down, diethyl ether was added to extract the product and separated from the reaction medium via centrifugation.Open in a separate windowScheme 1Recycling process of the Pd-mSi-PEG-5k-nanocatalyst and PEG-2000 as solvent after the Heck-reaction between ethyl acrylate and p-iodoanisole to form ethyl p-methoxycinnamate.To exclude any suspended compounds from the desired product, the mixture was passed through a PTFE-filter. Et₂O was removed in vacuo without the need of column chromatography. Comparing the ¹H-NMR spectra of the as-obtained product with the educts indicate a yield of 98% with only small amounts of PEG-2000 present (identified by the signal at ∼3.6 ppm, < 1 weight-%). The results show that both educts and the base Na₃PO₄ are able to diffuse through the mesoporous silica shell to the palladium core (see Fig. 3). A detailed ¹H-NMR signal assignment of the product is given in Fig. S5.^†Open in a separate windowFig. 3 ¹H-NMR spectra of the educts ethyl acrylate (top) and p-iodoanisole (center) and the product ethyl p-methoxycinnamate (bottom).After recovering the reaction mixture containing Pd-mSi-PEG-5k and PEG-2000, seven further Heck-reaction-cycles were conducted under the same conditions. Results obtained from ¹H-NMR and gravimetry indicate no significant decrease in catalytic activity (see ¹H-NMR spectra in Fig. 4). Along the eight Heck-reactions, product yields were determined between 94% and 99%. Only small traces of p-iodoanisole (identified by the signal at ∼6.75 ppm) were still present while ethyl acrylate could be fully removed in vacuo. The yields obtained after each cycle are displayed in Fig. 5. ICP-MS measurements of the catalysis product were performed to determine the palladium leaching out of the catalytic system. The results are displayed in Table S1^† indicating that leaching is strongly suppressed since the overall Pd-content in the product ranges from 0.3–5.7 ng, only. This corresponds to 0.002–0.044 ppm palladium with respect to the product mass. The data are in good agreement with the high product yields along the eight Heck-reactions. To trace the evolution of the nanocatalyst along the cycles, TE micrographs were taken after the 1^st and the 8^th Heck-cycle (see Fig. 6). It can be seen that the cubical structure of the palladium vanishes during the first reaction (left TEM image). Inside the silica shell spherical palladium particles were formed. An explanation for this rearrangement lies in the suggested Heck-mechanism.³⁵ Here, a Pd²⁺-species forms after the oxidative addition of the p-iodoanisole which can desorb from the Pd-NCube. Once the reductive elimination of the product occurs the Pd⁰-species is generated again that can re-deposit on the palladium-core.²¹ Since the spherical geometry possesses the lowest free surface energy, globules were eventually formed.³ The mesoporous silica shell is not affected significantly by the catalysis and the rearrangement of the palladium. The porosity appears to stay intact, enabling the penetration of further small organic molecules. Control experiments were performed to validate whether these observations are based on either a thermally or a chemically induced rearrangement process of the palladium core. Therefore, only the nanocatalyst was dispersed in PEG-2000 and heated at 110 °C for 24 h without any conducted catalysis reaction. TEM results showed no changes in the structure of neither the palladium core nor the silica shell (see Fig. S6^†). After the 8^th reaction, no core–shell-nanostructures could be detected anymore via TEM. Only small randomly shaped Pd-nanoparticles (≤20 nm) were found indicating a slow leaching of the palladium out of the silica shell. However, no larger aggregates were formed (see right TE micrograph in Fig. 6) which explains the continuously high catalytic activity.Open in a separate windowFig. 4 ¹H-NMR spectra of the product ethyl p-methoxycinnamate after the 1^st Heck-reaction (bottom) up to the 8^th reaction (top).Open in a separate windowFig. 5Conversions of ethyl p-methoxycinnamate obtained via NMR and gravimetry after each respective Heck-reaction (1–8).Open in a separate windowFig. 6TE micrographs of the Pd-mSi-PEG-5k-nanocatalyst taken after the 1^st (left) and the 8^th Heck-reaction (right).     

Electronic energy levels of porphyrins are influenced by the local chemical environment

Self-assembled islands of 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin (2HTFPP) on Au(111) contain two bistable molecular species that differ by shifted electronic energy levels. Interactions with the underlying gold herringbone reconstruction and neighboring 2HTFPP molecules cause approximately 60% of molecules to have shifted electronic energy levels. We observed the packing density decrease from 0.64 ± 0.04 molecules per nm² to 0.38 ± 0.03 molecules per nm² after annealing to 200 °C. The molecules with shifted electronic energy levels show longer-range hexagonal packing or are adjacent to molecular vacancies, indicating that molecule–molecule and molecule–substrate interactions contribute to the shifted energies. Multilayers of porphyrins do not exhibit the same shifting of electronic energy levels which strongly suggests that molecule–substrate interactions play a critical role in stabilization of two electronic species of 2HTFPP on Au(111).

Self-assembled islands of 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin (2HTFPP) on Au(111) contain two bistable molecular species that differ by shifted electronic energy levels.

The packing of two-dimensional self-assembled monolayers is facilitated by molecule–surface and molecule–molecule interactions. At low coverage, molecules with repulsive intermolecular interactions can adsorb at preferred surface-adsorption sites,^1–4 while at higher concentrations the preferred surface site may be sacrificed to increase density and maximize intermolecular interactions.^3–6 Surface adsorption can change the conformational structure of a molecule to maximize these interactions resulting in a conformational shape not found in bulk crystals or solvated molecules.^4,7–10 Rational manipulation of shape and local environment can fine tune the electronic properties of the adsorbate.Porphyrins consist of four pyrrole-like moieties connected with methine bridges. The high level of conjugation, with 18 π electrons in the shortest cyclic path, allow porphyrins to strongly absorb light in the visible region, 400–700 nm.^11–13 Porphyrins are known as the color of life molecule.^14,15 Heme, an iron–porphyrin complex, is responsible for transporting oxygen through the bloodstream and gives red blood cells their bright color.¹⁶ Chlorophyll, a partially hydrogenated porphyrin, is responsible for the green color in plants and plays a critical role in photosynthesis.¹⁶ The strong interaction with light, overall chemical stability, and diversity through functionalization makes pyrrolic macrocycles ideal candidates for use in photovoltaics,^17–21 chemical sensors,^22–25 catalysis,^26–28 and molecularly based devices.^29–32The existence of bistable switchable states is the first step towards use of porphyrins in applications of molecular memory storage or binary devices.³³ Pyrrolic macrocycles have been shown to exhibit bistable switching behavior on surfaces including induced conformational switching,^34–36 orientational flip-flopping,^37–41 and tautomerization.^42–46 Examples include subphthalocyanine arrays that adsorb with a shuttlecock shape and exhibit scanning tunneling microscopy (STM) induced reversible orientational switching on Cu(100),³⁷ and current from the STM tip that has been used to induce hydrogen tautomerization in naphthalocyanine on an NaCl bilayer on Cu(111).⁴²Confinement to two dimensions through adsorption of 2HTFPP onto a surface creates a complex heterogeneous environment with influences from the substrate and neighboring molecules. In this study, we characterize the local density of states of 2HTFPP adsorbed on Au(111), and found that the local chemical environment can cause the energies of molecular orbitals to shift. This creates an environment where chemically identical molecules exist as two species on the surface.The sample was prepared using an Au(111) substrate on mica (Phasis) that was cleaned through several rounds of annealing and argon sputtering. Images were collected at ultra-high vacuum and 77 K with a low-temperature scanning tunnelling microscope (LT-STM, Scienta Omicron) under constant current mode. The tips were mechanically etched 0.25 mm Pt80/Ir20 wire (NanoScience Instruments). The sample was prepared at room temperature by depositing 1 mM solution of 2HTFPP dissolved in dichloromethane via pulsed-solenoid valve in a vacuum chamber onto the clean gold or 2HTFPP dissolved in dimethylformamide via drop-casting and annealing to 200 °C.⁴⁷The electronic structure of 2HTFPP, neutral TFPP, and dianionic TFPP were calculated using density functional theory (DFT). The structures were optimised using the B3LYP^48,49 density functional approximation and the 6-311+G(d) basis set. A harmonic vibrational frequency analysis confirmed the structure was in a local minimum on the ground state potential energy surface without imaginary frequencies. All calculations were performed on Gaussian 16 Rev. A.03.⁵⁰ Simulated STM images were computed using the Tersoff and Hamann approximation^51,52 as done by Kandel and co-workers.^53,54 The tunneling current was modeled as a function of tip position, and the surface was modeled as a featureless and constant density of states to reproduce a constant current experiment. Through the Tersoff and Hamann approximation the tunneling current leads to information on the local density of states at a specific energy and a discrete location.Pulse-depositing 2HTFPP in vacuum via a pulsed-solenoid valve resulted in ordered islands of the adsorbate, Fig. 1. The formation of close-packed islands, despite submonolayer coverage, indicates attractive intermolecular interactions between adsorbates. 2HTFPP has a packing density of 0.64 ± 0.04 molecules per nm² with a 1-molecule unit cell and rectangular packing.Open in a separate windowFig. 1(a–c) Unoccupied and (d–f) occupied electron states of 2HTFPP. All scale bars are 5 nm. (e) Two bistable species, diffuse square outlined in green and a double-dot feature outlined in white. (f) 2HTFPP appears as double-dot features. The white box indicates the 1-molecule, rectangular unit cell. Images taken with a tunneling current of 5 pA.Changing the polarity of the bias voltage of the STM sample allows unoccupied (positive voltage) or occupied (negative voltage) molecular orbitals to be imaged along with the topography of the surface. The unoccupied electron states, Fig. 1a–c, have an even distribution of electron density across the molecule and appear as diffuse squares. As the magnitude of the bias voltage is increased, a larger number of electronic energy levels are included in the measurement. Increasing the magnitude of the negative bias voltage from −0.25 V to −1.5 V, Fig. 1d and f, results in a change in contrast from a diffuse square to a bright double-dot feature. Imaging at −0.75 V, an intermediate voltage between these two energy levels, we observe two species—a mixture of diffuse squares and double-dot features, Fig. 1e. These species are differentiated from one another by having the same ground state molecular orbitals at shifted energies. If all the molecules on the surface were equivalent, we would expect to image the same molecular orbitals of each molecule at each bias voltage. At −0.75 V we do not observe the same orbital shape for each molecule, but we observe influence of the HOMO−2 and HOMO−3 energy levels in approximately 60% of that adsorbed 2HTFPP. Interaction with the local chemical environment causes the energy levels to be shifted enough to be included at a bias voltage with a smaller magnitude.We investigated the possibility that the two species were chemically different. If a gold atom formed a complex with the porphyrin, we would expect the displacement of the inner pyrrolic hydrogens. It was also possible that the presence of the STM tip was altering the adsorbates. Smykalla et al. reported that the STM tip can reversibly remove and replace the pyrrolic hydrogens which changes the shape and contrast of the porphyrin in the STM images.⁵⁵ Deng and Hipps reported a small shift in orbital energies of 0.04 eV for vapor-deposited metallo-porphyrins on Au(111) due to the height of the tip.⁵⁶ We observed a march larger shift of orbital energies and used DFT to calculate shapes of the occupied and unoccupied molecular orbitals of gas phase 2HTFPP, TFPP with the inner pyrrolic hydrogens removed, dianionic TFPP with the inner pyrrolic protons removed, and Au-TFPP with a gold atom coordinated to the porphyrin, Fig. 1 in ESI.^† We used the electronic structure calculations to make theoretical STM images. We found that the double-dot feature was only present in the occupied orbitals of 2HTFPP, Fig. 2. Theoretical STM images of Au-TFPP, Fig. 2 in ESI,^† does not show the double-dot feature. This suggests that intact 2HTFPP molecules make up the close-packed islands, and both detected species are chemically equivalent. The shift in electronic energy levels is due to the heterogeneous local chemical environment.Open in a separate windowFig. 2DFT, theoretical STM images, and comparison with experimental STM images of 2HTFPP. HOMO and HOMO−1 have a diffuse square shape, while HOMO thru HOMO−3 exhibit the double dot feature. Both of these shapes were experimentally observed at −0.75 V.The packing of adsorbates is a balance between molecule–molecule and molecule–substrate interactions. We observed various packing densities and unit cells that were dependent on sample preparation. Preparation with the pulsed-solenoid valve at room temperature created a 1-molecule unit cell with a packing density of 0.64 ± 0.04 molecules per nm², Fig. 1. Annealing the sample to 200 °C resulted in a 1-molecule unit cell with a packing density of 0.38 ± 0.03 molecules per nm², Fig. 4. Annealing altered both the adsorption sites and intermolecular ordering of 2HTFPP, and we no longer observed two electronic species on the surface. Annealing to 200 °C may remove excess solvent and provide the energy needed for the adsorbed species to leave the preferred adsorption site and maximize intermolecular interactions. This suggests that the local chemical environment plays a critical role in the creation of two bistable species. The surface of Au(111) undergoes herringbone reconstruction with packing of the surface gold atoms.^57,58 The surface consists of both face-centered cubic packing (fcc) and hexagonally-close packed (hcp) gold atoms with strained transition areas. The three different domains create a heterogeneous surface electronic structure.⁵⁹ To investigate the relationship of species 1 and species 2 with the underlying substrate we characterized the images using Fast Fourier Transform (FFT). FFT converts an image from real space to frequency space and can reveal longer-range ordering of molecular assemblies.Open in a separate windowFig. 42HTFPP after annealing to 200 °C. The unit cell has dimensions of 1.6 nm × 1.6 nm and the monolayer has a packing density of 0.38 molecules per nm². The bright double-dot features are doubly stacked porphyrins, the start of a second layer. The image was taken with a bias voltage of −10.0 mV and a tunneling current of 10 pA.In order to focus the FFT on one species at a time, white circles were placed over each double dot feature, Fig. 3a and b. FFT were taken of the images with the circles to determine the packing of the adsorbates, Fig. 3c and d. Hexagonal ordering as well as longer-range rectangular packing can be seen in the FFT, Fig. 3c, of the locations of the double-dot features in the image showing two species of 2HTFPP, Fig. 3a. We observed rectangular packing of 2HTFPP when the magnitude of the bias voltage was large enough for all of the adsorbed porphyrins to exhibit bright double-dot features, Fig. 3b and d. The presences of hexagonal packing for one species, but not the overall self-assembled island suggests that the adsorption site on the underlying gold herringbone reconstruction is playing a role in the shift of electronic energy levels. We did not observe the two species after annealing to 200 °C, suggesting that solvent and intermolecular interactions may influence the location of the adsorption site on Au(111). We also observed that the double-dot features in Fig. 3a were more likely to exist around molecular defects and edges of the close-packed island suggesting that intermolecular interactions also play a role in the shift of the electronic energies of the molecular orbitals.Open in a separate windowFig. 3(a) Circles placed over each 2HTFPP molecule with bright double dot features at −0.75 V and (b) −1.5 V (c) is FFT of (a) showing hexagonal order (d) is FFT of (b) showing rectangular order.Pulse deposition with a solenoid valve into vacuum has been shown to create meta-stable molecular motifs due to the rapid evaporation of solvent.⁵³ We planned to directly compare room-temperature pulse deposition with drop-casting but were unable to resolve drop-cast porphyrins prior to annealing. Drop-casting followed by annealing resulted in an alternate packing of 0.21 molecules per nm², Fig. 3 in ESI.^† Despite the fluorinated phenyl group inverting the polarity of the ring, we observe π stacking of pentafluorophenyl rings after pulse-depositing and annealing to 200 °C, Fig. 4. Although this is unexpected, Blanchard et al. have previously observed face-to-face π stacking in the crystal structure of pentafluorophenyl substituted ferrocenes.⁶⁰Several molecules on top of the self-assembled island, the start of a second layer, appear with bright double-dot features, Fig. 4. We did not observe the coexistence of two electronic species in the second layer of 2HTFPP.In conclusion, we observed two bistable species of 2HTFPP on Au(111) with non-degenerate electronic energy levels. DFT and theoretical STM images suggest that the two species are both 2HTFPP and not chemically altered through adsorption or interaction with the STM tip. The species with the affected electronic energy levels appear near molecular vacancies and exhibit longer-range hexagonal packing indicating that the two species are created through molecule–substrate and molecule–molecule interactions. Annealing to 200 °C decreases the packing density and alters the molecule–molecule and molecule–surface interactions. Adding a second layer of adsorbate only exhibits one electronic species which strongly suggests that the local chemical environment plays a critical role in the shift of the electronic energies of the molecular orbitals of 2HTFPP.     

A solid-phase approach for the synthesis of α-aminoboronic acid peptides

A solid-phase synthesis of α-aminoboronic acid peptides using a 1-glycerol polystyrene resin is described. Standard Fmoc solid-phase peptide chemistry is carried out to construct bortezomib and ixazomib. This approach eliminates the need for liquid–liquid extractions, silica gel column chromatography, and HPLC purifications, as products are isolated in high purity after direct cleavage from the resin.

A solid-phase synthesis of α-aminoboronic acid peptides using a 1-glycerol polystyrene resin is described.

α-Aminoboronic acids are currently being investigated for their utility as reversible covalent inhibitors in a diverse range of therapeutic applications (Fig. 1).¹ These compounds'' Lewis acidity enables the formation of stable tetrahedral adducts with nucleophilic residues in biological targets (Fig. 2). In 2003, the first boronic acid drug, bortezomib, was approved for the treatment of multiple myeloma.² Ixazomib, a related α-aminoboronic acid inhibitor, was later approved in 2015 for the same indication.³Open in a separate windowFig. 1α-Aminoboronic acids featured in various drug discovery programs. Flaviviral protease inhibitor (1), HCV protease inhibitor (2), LepB inhibitor (3).Open in a separate windowFig. 2Yeast 20S proteasome in complex with bortezomib (PDB ID 2F16). The boronic acid forms a stable tetrahedral adduct with the N-terminal threonine (Thr1).Peptidic α-aminoboronic acids, such as bortezomib and ixazomib, have traditionally been assembled using standard peptide coupling techniques,⁴ wherein an α-aminoboronic ester is introduced onto a pre-constructed peptide and is subsequently deprotected to unmask the boronic acid. Metal-catalyzed decarboxylative borylation strategies have also been reported for the preparation of α-aminoboronic acid peptides.⁵ This approach provides direct access to these compounds from their parent peptide constructs but sacrifices stereochemical integrity.Regardless of the method, α-aminoboronic acid/ester peptides are difficult to prepare for a number of reasons.⁶ First, the C–B bond can be oxidatively labile.⁷ Second, α-aminoboronic acids and esters containing an unsubstituted α-amino group can undergo a spontaneous 1,3-rearrangement (Scheme 1, A); this process can be minimized or suppressed entirely if the amino group is rapidly acylated or protonated.⁸ Third, boronic esters can be hydrolytically labile, especially at low pH (Scheme 1, B).^6,9 Therefore, any multistep approach must entail careful extractive workups and purifications to ensure that the ester remains intact.Open in a separate windowScheme 1General considerations for preparing α-aminoboronic acid peptides.While solid-phase peptide synthesis (SPPS) has become a standard method for the construction of peptides,¹⁰ this technology has remained underexplored for the preparation of α-aminoboronic acid peptides.¹¹ An approach of this type could eliminate liquid–liquid extractions and HPLC purifications and could enable high-throughput access to this class of compounds. To the best of our knowledge, there has only been one report of C-terminal SPPS to generate α-aminoboronic acid peptides (Scheme 2).¹² Although this study provides a critical conceptual foundation, the approach it describes lacks the simplicity of a traditional solid-phase approach, requiring a complex 8-step synthesis to prepare resin-bound α-aminoboronic ester 6 for SPPS. This limitation may preclude its use as a general strategy for the preparation of α-aminoboronic acid peptides.Open in a separate windowScheme 28-Step preparation of a resin-bound α-aminoboronic acid for C-terminal SPPS.We sought to identify an approach that could enable access to resin-bound α-aminoboronic acids for SPPS in a limited number of steps using the emerging supply of commercially available α-aminoboronic acid building blocks. The Klein group recently described the use of a 1-glycerol polystyrene resin that could be used for Fmoc SPPS to construct boronic acid-containing peptides.^13–15 These results prompted us to explore the use of this resin for preparation of α-aminoboronic acid peptides, specifically bortezomib and ixazomib.Considering the unique reactivity of α-aminoboronic acids, we needed to devise a concise loading strategy that would suppress the potential for C to N boron migration. This required the amine to remain protonated or acylated throughout the loading process. These considerations lead to the design of a two-step loading protocol (Scheme 3). Commercially available boroleucine pinanediol ester 7 was hydrolysed with aqueous HCl. The boroleucine salt (8) was isolated in quantitative yield, free of pinanediol impurities, after a simple liquid–liquid extraction. The crude boroleucine salt was then shaken with the 1-glycerol polystyrene resin (loading capacity 0.6 mmol g⁻¹),¹³ Fmoc chloride, and N,N-diisopropylethylamine to provide resin-bound Fmoc-protected boroleucine 9.Open in a separate windowScheme 32-Step protocol for loading boroleucine onto a 1-glycerol polystyrene resin.With the C-terminal α-aminoboronic acid resin in hand, we used standard Fmoc SPPS coupling techniques¹⁶ to synthesize bortezomib (Scheme 4). Fmoc deprotection (piperidine, DMF) and amide coupling (Fmoc-Phe-OH, TBTU, N,N-diisopropylethylamine, DMF) delivered intermediate 10. A subsequent Fmoc deprotection/coupling sequence with pyrazinecarboxylic acid produced resin-bound bortezomib 11. Hydrolysis of the resin bound peptide was accomplished with gentle shaking in a THF/water mixture.¹³ Filtration and concentration delivered bortezomib (7-steps from boroleucine pinanediol ester 7) in 54% yield and in >95% purity.Open in a separate windowScheme 4Solid-phase synthesis of bortezomib.The synthesis of ixazomib (Scheme 5) was accomplished in an analogous manner. Fmoc deprotection (piperidine, DMF) and amide coupling (Fmoc-Gly-OH, TBTU, N,N-diisopropylethylamine, DMF) delivered intermediate 12. The deprotection/coupling sequence was repeated with 2,5-dichlorobenzoic acid to generate resin-bound ixazomib 13. Finally, boronic ester hydrolysis (THF/water) provided ixazomib in 49% yield and in >95% purity.Open in a separate windowScheme 5Solid-phase synthesis of ixazomib.     

Synthesis of fully protected trinucleotide building blocks on a disulphide-linked soluble support

In recent years, preparation of fully protected trinucleotide phosphoramidites as synthons for the codon-based synthesis of gene libraries as well as for the assembly of oligonucleotides from blockmers has gained much attention. We here describe the preparation of such trinucleotide synthons on a soluble support using a disulphide linker.

Fully protected trinucleotides are synthesized on a tetrapodal soluble support using a disulphide linkage that upon reductive cleavage allows release of the trinucleotide with free 3′-OH group for further conversion to a phosphoramidite.

The synthesis of fully protected trinucleotide synthons for codon-based assembly of oligonucleotides has a long history and originally was motivated by the need for methods of combinatorial and evolutionary protein engineering, which combine combinatorial gene synthesis with functional screening or genetic selection applied at the phenotype level to an ensemble of many structural variants generated in parallel.^1–3 Among a host of related methods, the use of mixtures of pre-formed trinucleotide blocks representing codons for the 20 canonical amino acids stands out as allowing fully controlled randomization individually at any number of arbitrarily chosen codon positions of a given gene.^4–6 The chance of functional proteins in such libraries is increased, as randomization independent from the degenerated genetic code is possible and thus bias to amino acids represented by more than one codon as well as stop codons can be avoided.^6–9 The power of this method has been successfully demonstrated for randomization of immunoglobulins or at the example of a gene library of tHisF from the hyperthermophile Thermotoga maritima.^7,10 Apart from the preparation of gene libraries with controlled randomization, fully protected trinucleotides have potential as building blocks for oligonucleotide synthesis from blockmers (n = 1, 2, 3, 4, …), in particular then, when the oligomer is composed of repetitive sequence patches. In an ideal case, one previously synthesized blockmer can be coupled several times to obtain the desired oligomer. Moreover, oligonucleotide assembly from blockmers is advantageous in terms of easier purification, since n − 1, −2, … side products cannot be formed. A number of routes to fully protected trinucleotide building blocks have been developed, based on strategies in solution, on solid phase or on soluble supports (Fig. 1).^4,11,12 Traditionally, trinucleotide synthons have been prepared in solution, paying special attention to the pair of orthogonal protecting groups for the 5′- and 3′-OH functions, when synthesizing a dinucleotide that subsequently can be extended in 5′- or 3′-direction.^1,13–19Open in a separate windowFig. 1Strategies for preparation of fully protected trinucleotides in solution (A), on solid support (B) and on soluble phase (C); PG = protecting group.Synthesis in solution requires isolation of products after each synthesis step, which can become rather tedious. Therefore, we^11,20 and others¹⁹ have developed strategies for trinucleotide synthesis on solid support as an attractive alternative to protocols in solution.The key issue is the attachment of the 3′-start nucleoside to the solid support via a suitable linker, allowing to cleave off the trinucleotide after synthesis without loss of the protecting groups. With regard to trinucleotide synthesis, an oxalyl anchor¹⁹ or a disulphide linker have been described.^11,21In recent years, protocols for the synthesis of oligonucleotides on soluble supports have emerged,^12,21–24 and those have also been used with particular attention to the preparation of fully protected trinucleotides.^12,21 The general strategy involves iterative cycles of reaction steps in solution and precipitation for isolation/purification of reaction products. Several soluble supports have been used for oligomer synthesis (reviewed in ref. 25), among those, pentaerythritol-derived cores, which are easily precipitated from methanol.²⁴ Fully protected trinucleotides have been prepared on the pentaerythritol-derived core with the start nucleoside being tethered to the polymer via a disulphide bridge²¹ or hydroquinone-O,O′-diacetic acid (Q-linker).¹² In both strategies, phosphotriester chemistry has been used for trimer assembly, which in the disulphide strategy resulted in a trinucleotide with 3′-terminal ortho-chlorophenylphosphate.²¹ This 3′-remnant may be activated as a phosphotriester, but in standard automated DNA synthesis, where phosphoramidite coupling is strongly preferred, it would require to be selectively removed in order to convert the trinucleotide to the 3′-O-phosphoramidite building block. Moreover, the reductive cleavage of the disulphide bridge was performed in conditions that caused premature loss of the 5′-dimethoxytrityl (DMT) protecting group.²¹Based on our previous experience,^11,14,20 we here report on the preparation of fully protected trinucleotides on a pentraerythritol-derived soluble support using phosphoramidite chemistry for nucleotide coupling. As we have reported previously, tethering the start nucleoside to a solid support (polystyrene) via a dithiomethyl linkage is a superior strategy for assembly of blockmers that upon release from the support by reductive cleavage carry protecting groups at all functionalities, but offer a free 3′-OH group for conversion to the phosphoramidite building block.^11,20 Application of this immobilization strategy to the pentaerythritol-derived core, first required appropriate functionalization of the core. This was achieved as described previously by conjugation of commercially available S-propargyl thioacetate to the tetrakis-O-[4-(azidomethylphenyl)pentaerythritol] support²¹ by Cu(i) catalyzed 1,3-dipolar cycloaddition,^26,27 yielding tetrakis-O-{4-[4-[(acetylthiomethyl)]-1H-1,2,3-triazol-1-ylmethyl]-phenyl} pentaerythritol (1) (Scheme 1). The 3′-O-methylthiomethyl (MTM) modified start nucleosides (T and Bz-dA) were synthesized as described²⁰ following the strategy originally developed for synthesis of 2′-O-DTM functionalized ribonucleotide building blocks.²⁸ Aminolysis of the thioacetate on the support with butylamine in methanol delivered the free thiol function (2) required for immediate reaction with the nucleoside derivative to form the disulphide linkage. To this end, the 3′-O-MTM functionalized nucleoside (3a–b) was activated by treatment with sulfuryl chloride to give the 3′-O-chloromethyl ether (4a–b) in a Pummerer rearrangement, which immediately was converted in the presence of potassium thiotosylate to the reactive species (5a–b). This subsequently reacted with the support bound thiol (2) to form the desired loaded tetrapodal soluble support (6a–b, Scheme 1).Open in a separate windowScheme 1Reaction scheme for coupling of start nucleoside to soluble support.To start trinucleotide assembly, the support carrying the start nucleoside (6a–b) was treated with 4% dichloroacetic acid in ethylene dichloride to cleave off the 5′-O-DMT group (Fig. 2). The acid treatment was quenched by addition of pyridine, the solvents were evaporated, and the support linked with the deprotected start nucleoside (7a–b) was precipitated from methanol. The coupling reaction was carried out by taking up the precipitate in acetonitrile containing six equivalents of the N-acyl-5′-O-DMT protected nucleoside phosphoramidite in 0.1 M concentration, and addition of benzylmercapto-tetrazole²⁹ as activator. The resulting dimer 8a–b was oxidized by addition of a 0.2 M solution of iodine in trimethylpyridine/ACN/H₂O (1/11/5) to give the dinucleotide product 9a–b (Fig. 2). The support-linked dinucleotide 9a–b was directly precipitated from the reaction mixture by addition of methanol. The solid was filtered off and used for the next coupling cycle. All steps including deprotection, coupling and oxidation were repeated to obtain the fully protected trinucleotide on the soluble support (10a–b–12a–b, Fig. 2).Open in a separate windowFig. 2Reaction scheme of trinucleotide assembly on soluble support.NMR spectroscopy was used to analyse success of the synthesis. However, as long as the start nucleoside as well as the intermediate dinucleotide and the final trinucleotide were bound to the soluble support, complexity of the products and their modest solubility in common deuterated solvents retarded the analysis. Consequently, detailed NMR characterization was applicable only for the products released from the support. After assembly of the trinucleotide was finished, it was released in fully protected form from the support by reductive cleavage of the disulphide linkage with TCEP at pH 7.5 ³⁰ (13a–b, Fig. 2). After treatment with TCEP, the support was thoroughly washed with acetonitrile, acetone, ethanol and ethyl acetate, in order to separate the cleaved off trinucleotide. Traces of TCEP and of the tetrapodal support, which remained after this work up, were finally removed by chromatographic purification, which yielded sufficiently pure trinucleotide blockmers CTA and GGT in 43% and 35% overall isolated yield, respectively (both synthesized in tens of μmol scale). Extensive analysis by various NMR techniques (¹H, ¹³C, DEPT, HSQC, DQF-COSY, for detailed information see ESI^†) unambiguously confirmed the identity and purity of the desired products. For further application as synthons for DNA synthesis, the trinucleotides were converted to 3′-O-methylphosphoramidites following the standard procedure for phosphitylation (Fig. 3).³¹ The methyl group was chosen for protection of the phosphorous, because of its higher stability as compared with the β-cyanoethyl group and thus easier handling. Nevertheless, it should be noted, that also β-cyanoethyl protection can be used, both for the phosphate moieties in the trinucleotide and in the final trinucleotide 3′-O-phosphoramidite, if all steps of synthesis, purification and storage are carried out with particular care, partially requiring specific conditions.¹⁴ After aqueous work up and extensive drying, 0.1 M solutions of both trinucleotide phosphoramidites in appropriate solvents (see below) were prepared and used for coupling on the DNA synthesizer. Both trinucleotide synthons CTA (14a) and GGT (14b) were coupled in individual syntheses onto a short oligomer (CTT) on CPG. The 5′-terminal DMT group was left on, and the resulting 6mers 5′-CTACTT-3′ and 5′-GGTCTT-3′ were cleaved from the support by concentrated ammonia. RP-HPLC analysis was used to evaluate the coupling efficiency of the trinucleotide blockmers (Fig. 4).Open in a separate windowFig. 3Reaction scheme of trinucleotide phosphitylation, (i) N,N-diisopropyl-methyl-phosphonamidic-chloride, TEA, DCM, 3.5 h, rt; PG = protecting group.Open in a separate windowFig. 4HPLC analysis of CTACTT (A) and GGTCTT (B) (DMT-on). (A) peak 1: abortive fragments, peak 2: CTACTT; (B) peak 1: abortive fragments, peak 2: GGTCTT; AU = absorption unit. Conditions for (A and B) nucleodur 125/4, CV = 1.571 ml, 1 ml min⁻¹; buffer (A) 5% ACN, 0.1 M TEAAc; buffer (B) 30% ACN, 0.1 M TEAAc; gradient: starting with 0% buffer (B) for 4 CV, to 40% buffer (B) over 3 CV, to 60% buffer (B) over 7 CV, to 100% buffer (B) over 2 CV, then 100% buffer (B) for another 2 CV, to 0% buffer (B) over 3 CV.It has been discussed in the past that some but not all trinucleotide synthons are soluble in acetonitrile^1,32 or various compositions of acetonitrile–dichloromethane mixtures^12,16,19 with or without addition of DMF.¹⁸ The fully protected trinucleotide CTA showed poor solubility in acetonitrile and therefore was dissolved in dichloromethane. Solubility was clearly better than in acetonitrile, but not fully satisfying. Accordingly, HPLC analysis of the 6mer after coupling and deprotection showed a rather low coupling yield (Fig. 4A). This result may be interpreted as a consequence of a low effective concentration of the CTA blockmer and of the missing acetonitrile being the ideal solvent for phosphoramidite coupling. For dissolving the second trinucleotide GGT, we applied a 3 : 1 mixture of dichloromethane and acetonitrile, which allowed to prepare a 0.1 M solution of the trinucleotide phosphoramidite ready for coupling. A double coupling cycle was used to increase the coupling efficiency. The results are shown in Fig. 4B. A clearly higher coupling yield was achieved for the trinucleotide synthon GGT as compared to CTA (Fig. 4A). HPLC peak areas designated as final 6mers and abortive fragments would give rough estimation for the coupling yields, being about 17% for the CTA synthon and 72% for the GGT synthon under the described conditions (see ESI^† for details). The identity of the assembled 6mers was confirmed by MS analysis (see ESI^†). For GGT, the estimated coupling yield is well in the range of that for trinucleotide synthons reported in the literature,^15,16,32 although the coupling yields given there are usually just concluded from detritylation values on the synthesizer,^1,12,18,32 or it is not at all specified how those were determined.^15,19 Therefore, it is difficult if not impossible to compare coupling yields among the different protocols. Trinucleotide synthons that we had prepared in the past, showed coupling yields in DNA synthesis comparable to that achieved here in the range of 70 to 90%.¹⁴ This certainly can be further optimized in a systematic study including various solvents and solvent compositions for trinucleotide phosphoramidites, which however would require larger amounts of trinucleotide synthons than produced here. The focus of this work is on preparation of the trinucleotides on a soluble support, which has been successfully achieved, and the general functionality of the prepared trinucleotide synthons in automated DNA synthesis was demonstrated, although suitable conditions for efficient coupling still need to be determined.     

Ultra-high adsorption of cationic methylene blue on two dimensional titanate nanosheets

In this work, we examined the performance of 2D titanate nanosheets for dye adsorption. Their adsorption capacity for methylene blue (MB) is up to 3937 mg g⁻¹, which is more than 10 times higher than active carbon and occupies the highest place among all the reports.

2D titanate nanosheets show ultra-high adsorption for methylene blue.

Dyes are important materials in many industries such as the textile, paper, leather, printing, and plastic industries. However, the dye effluents released by these industries give rise to major environmental issues because the dyes are generally toxic and/or carcinogenic to human beings.¹ Dye removal from the wastewater is essential before release in these industries. There are several methods to remove dye contaminants from wastewaters, such as adsorption, coagulation, chemical oxidation, membrane separation processes, etc.¹ Among the technologies, the adsorption process has been generally considered to be the most efficient method of quickly lowering the concentration of dissolved dyes in an effluent.² Various adsorbents have been studied for dye removal purposes, such as activated carbons (ACs),^3–6 clay,^7,8 sawdust,⁷ beer brewery waste,² chitosan,⁹ metal oxides,^10–12 carbon nanotubes and graphene oxide.^13,14 A general strategy to enhance the dye adsorption is to increase the surface area of the adsorbents, so the nanosized materials have been attracting much attention for the dye removal application because they exhibit much large surface area.^14–20Two dimensional (2D) materials are gaining great attention since discovery of graphene.^21–23 The 2D materials consist of large number of groups, such as graphene, transition metal dichalcogenides (TMDs), transition metal oxides (TMOs), layered double hydroxides (LDHs), MXene et al.^21,24–26 One may divide the 2D materials into three groups based on the charge of the host layer: neutral, negatively charged, and positively charged. The charged 2D materials must couple with counterions to compensate the charges. As a sample, 2D titanium oxide, also called titanate nanosheet (TONS) is negatively charged. The TONS is generally synthesized by the chemical exfoliation.^27,28 These chemical exfoliated TONS is monolayer nanocrystals with crystallographic thickness of 0.75 nm.²⁹ The nanosheets in aqueous solution behave as individual molecular entities, and they are surrounded by positively charged ions (TBA⁺ and H⁺).^28,30,31 The colloidal system is governed by electrostatic interaction.³¹As an emerging class of materials, the charged 2D materials are potentially useful for treatment of the dyes with opposite charges. This has motivated us to study the performance of the titanate nanosheets, a charged 2D material, for dye treatment.We synthesized the titanate nanosheets via top down approach report by Sasaki et al.^32,33Fig. 1a and b show the XRD pattern and SEM image of the protonated titanate. The XRD pattern is consistent with the previous report by Sasaki et al.^32,33 The SEM image shows that the crystal size is up to 20 μm. Fig. 1c shows the UV-Vis spectrum of the exfoliated titanate nanosheets. The peak is located at 265 nm, which is consistent with the value in the previous reports.^28,29,34Fig. 1d shows the STEM image of the nanosheets obtained by chemical exfoliation, and provides an evidence for the successful exfoliation. The AFM image of the nanosheets transferred to Si substrate by simple adsorption shown in Fig. S1^† shows the lateral size of the adsorbed nanosheets is generally less than 1 μm.Open in a separate windowFig. 1The XRD (a), SEM image (b) of protonated titanate; UV-Vis spectrum (c) and STEM image (d) of 2D titanate nanosheets. The dash line in (c) indicates the position of 265 nm.We first evaluated the adsorption capacity of the exfoliated nanosheets comparing with its bulk counterparts K_0.8[Ti_1.73Li_0.27O₄] (KLTO) and its protonated form (HTO). Fig. 2a shows that the adsorption capacity and adsorption percentage of the TONS in the function of the initial concentration of MB. The observed adsorption capacity increased up to 2236 mg g⁻¹ as the initial MB concentration was 4000 mg l⁻¹. It is noted that this value is underestimated because we didn''t consider the MB loss in experimental process. We analyzed the adsorption isotherm by fitting it with the Freundlich and the Langmuir models and the fitting curves are shown in Fig. 2b. The Langmuir model was fitting better than the Freundlich model, and the correlation coefficients R² for the Langmuir and the Freundlich models are 0.97 and 0.93, respectively. The better Langmuir model fitting indicates that the adsorption of MB on TONS surface is homogenous.¹¹ The maximum adsorption capacity fitted by the Langmuir model is 3937 mg g⁻¹. This adsorption capacity is, to the best of our knowledge, the largest for the MB adsorption among all the reports (see Table S1 in the ESI^†).^1,15–17,35 However, the dye removal efficiency is low even at the low initial concentration. Only half even less dye can be adsorbed as shown in Fig. 2a. Fig. 2c shows the morphology of the TONS after the MB adsorption at initial concentration of 1000 mg l⁻¹. The 2D feature of the TONS is clearly presented, indicating its good structural stability. In contrast to the large adsorption capacity of the TONS, its layered counterparts KLTO and HTO show limited adsorption capacity as shown Fig. 2d (see the adsorption data for KLTO in Fig. S2^†). Our data show that the adsorption capacities of the KLTO and HTO are 3.45 and 2.63 mg g⁻¹, respectively.Open in a separate windowFig. 2(a) The adsorption capacity and adsorption efficiency of titanate nanosheets at different initial concentrations; (b) the adsorption isotherm fitting with the Freundlich and the Langmuir models; (c) the typical morphology of TONS after MB adsorption (the initial concentration at 1000 mg l⁻¹); (d) the UV-Vis spectra of MB solution with concentration of 10 mg l⁻¹ before and after HTO adsorption. Fig. 3a presents the UV-Vis spectra of the MB (10 mg l⁻¹) and the TONS solution centrifuged at different time. The TONS shows rapid adsorption of the MB molecules. The concentration of the MB monomers dropped to a negligible concentration within 1 min, and a new peak appeared at ∼575 nm (purple by naked eyes) which can be assigned to the trimer form of the MB.^36–38 It is noted that the adsorption of MB monomers onto the TONS is much faster than other material systems, such as clay and graphene oxide.^14,39 The reason beyond this phenomenon is probably due to the large surface area and high charge density. It has been reported that the external adsorption of the MB is a fast process comparing with the internal adsorption in the clay system.³⁹ In this work, the TONS were dispersed in aqueous solution, so the external adsorption was dominating in the adsorption process. Another interesting feature is that the concentration of the MB trimers increased as the time proceeded. Because the MB monomers had been adsorbed onto the TONS within 1 min, the increase of the MB trimer concentration after 1 min suggests that the MB trimers came from desorption of the MB from the TONS. We analyzed the kinetic of trimer formation by assuming that the MB⁺ ions participating formation of trimer are irrelevant to the kinetic of desorption of MB–TONS complex, and we found the third order kinetic model is the best fitting to the experimental data among first, second and third order kinetic models, see Fig. 3b. The third order kinetic model yielded the correlation coefficient value of 0.965, while the first and second order kinetic models yielded the correlation coefficient values of 0.909 and 0.948, respectively. The data suggest that recombinative molecular desorption occurred, that is, multiple MB molecules desorbed and formed trimers. The desorption of counterions on the TONS was also observed with the TBA⁺ ions because the TBA–TONS complex went through an ionization process in the course of time.⁴⁰ The data here suggest the MB–TONS complex also went through an ionization process in the course of time after the rapid combination.Open in a separate windowFig. 3(a) UV-Vis spectra of MB and titanate nanosheets solution centrifuged at different time. (b) The trimer adsorption intensity vs. t for describing the desorption kinetics of methylene blue (10 mg l⁻¹) on the TONS.We also investigated the effect of the initial concentration of the MB on adsorption. Fig. 4a shows the UV-Vis spectra of residual (equilibrium) solution at different initial concentrations. The data show that the trimers were the main product after desorption at low concentrations (<100 mg l⁻¹), while the dimers (peak position at ∼615 nm) appeared and became more and more pronounced at high concentrations (>300 mg l⁻¹). We plotted the intensity change of monomers and dimers in reference to trimers in Fig. 4b. It is clear that the intensity of monomers didn''t change significantly in reference to trimers, but the intensity of the dimers did when the initial concentration of the MB solution increased, especially at 500 mg l⁻¹. It is noted that one should not compare the absolute values instead of the trend in the curves. The right vertical axis in the Fig. 4b presents the ratio of active surface area of adsorbed MB : TONS in the function of initial MB concentration in our study. We calculated the values assuming the MB molecules have only one side active to occupy the surface of the TONS. Fig. 4b shows that the number of the adsorbed MB⁺ ions was sufficient to cover the entire TONS surface and the second layer of the MB⁺ formed on the TONS surface when the initial concentration of MB solution reached 300 mg l⁻¹. Taking into consideration that the dimer started forming at the initial concentration of 300 mg l⁻¹, (see Fig. 4a) and the dimer formation enhanced further as the MB⁺ concentration increased, these data suggest that the formation of first layer MB⁺ on TONS surfaces suppresses the formation of trimers and promotes the formation of dimers. This is reasonable because the formation of first layer MB⁺ reduces the charge density of the MB–TONS complex. Bujdák et al. report that the high charge density of clay induces high order agglomeration of MB dye and low charge density suppresses the agglomeration.⁴¹ In our study, the charge density of the TONS remains constant, but the surface charge density of nanosheet complex changes with different amount of MB adsorption. The charge density of the MB–TONS complex determines the yield either trimer or dimer.Open in a separate windowFig. 4(a) UV-Vis spectra of residual (equilibrium) solution, (b) the intensity change of the monomer and dimer in the reference with trimer and the ratio of active surface area of adsorbed MB : TONS (the red dash line marks the position of left vertical axis at 1).In these colloidal systems, the TONS complex is governed by electrostatic force.³¹ According to the double layer theory, the TONS should be tightly bounded with the counterions such as MB⁺, TBA⁺ and H⁺ in first layer. In our solutions which are very basic, the concentration of these ions is in following order, TBA⁺ (0.0129 mol l⁻¹) > MB⁺ (0.00313 mol l⁻¹ for 1000 mg l⁻¹) ≫ H⁺. So, the TBA⁺ and MB⁺ ions are the main contributors to build the first layer. Given the size of the MB⁺ molecules 1.7 × 0.76 × 0.33 nm, the charge density is calculated to be 1.78q_e/nm² (where q_e is the electron charge) in the form of perpendicular to the TONS.⁴² In reality, the charge density should be smaller than this value because MB molecules are preferable to bound with TONS at certain angle. For example, the angle was found to be 65–70 °C on mica surface.⁴¹ The charge density of the TBA⁺ and NSTO is 1.63 and 4.72q_e/nm², respectively.²⁸ Therefore, one layer of the TBA⁺ and MB⁺ ions is insufficient to compensate the charge on the TONS surface. The TBA⁺ and MB⁺ ions in second and outer layers are necessary, but are loosely attracted to the TONS by the Coulomb force. The large dye adsorption capacity is probably due to this multilayer dye molecule adsorption behavior and the large surface area of the TONS. The mechanism of the ultra-high adsorption is to be verified.In summary, we studied the charged TONS for the MB adsorption treatment. We found that the TONS possess an ultra-high dye adsorption, and the adsorption capacity of titanate nanosheets is found up to 3937 mg g⁻¹. However, our data show that the dye removal efficiency of titanate nanosheets is low as less than 50%. Based on our analysis, we conclude that the large dye adsorption capacity is due to the large surface area of the TONS and the multilayer dye molecule adsorption behavior because of the presence of the surface charge. Furthermore, our study shows that the adsorption is a rapid process, and the loosely adsorbed MB molecules go through desorption to form high order agglomerates in the course of time. Our analysis indicates the desorption process a recombinative molecular desorption. What''s more, the product after desorption varies with the initial concentration of MB. Low concentration yields trimers, and high concentration promotes formation of dimers.It is well known that MB is a well-used redox indicator for photocatalysis study, at the end, we would like to highlight that one should use MB as the indicator more carefully because the color change may not be always due to the catalytic effect.     

Synthesis of a metal–organic framework by plasma in liquid to increase reduced metal ions and enhance water stability

Synthesis of a metal–organic framework by plasma in liquid was demonstrated with HKUST-1 as an example. HKUST-1 synthesized by this method contains a higher amount of monovalent copper ions than that synthesized by other conventional methods. The enhanced water stability was also confirmed.

Plasma in liquid provides a method for the synthesis of HKUST-1 with increased reduced metal ions and high water stability.

Metal–organic frameworks (MOFs) are a class of hybrid materials composed of organic linkers and metal nodes. They have high surface areas with tunable pore size and functionality.^1,2 Because of these features, MOFs have potential applications in the fields of gas adsorption/storage,^3,4 catalysis,^5,6 drug delivery,^7,8 and fabrication of luminescent materials.^9,10 Many methods have been proposed for synthesizing MOFs; these include solvothermal methods,^11,12 microwave-assisted methods,^13,14 ultrasonic-assisted methods,^15,16 mechanochemical methods,¹⁷ and electrosynthesis methods.¹⁸ Different synthesis methods result in the different crystallinity and size. Further, the synthesis method can influence the physicochemical and semiconductor properties.¹⁹Recently, a method for synthesizing MOFs in liquid contacting gas-phase dielectric barrier discharges has been reported.^20,21 However, MOFs synthesized by plasma have not been sufficiently characterized yet, thereby demanding further research. Plasma is a unique reaction field and has the advantage of being able to reduce and functionalize species using electrons and radicals. These characteristics have been widely utilized even in liquid phase for the synthesis of various materials such as carbon materials^22,23 and metal nanoparticles^24,25 and for introducing functional groups in materials.²⁶ Using plasma, it may be possible to synthesize functional MOFs with reduced metal ions or additional functional groups. Plasma in liquid generally have higher density of electrons and radicals than plasma in the gas phase,²⁷ and the influence of reactive species can be observed more prominently.In this study, we focused on [Cu₃(BTC)₂]_n (BTC = 1,3,5-benzenetricarboxylate). This is known as HKUST-1 and is one of the most widely researched MOFs. This MOF is assembled from copper nodes and BTC, with each copper coordinated with four oxygen atoms. HKUST-1 is a promising candidate for applications such as H₂ and SO₂ storage.^28,29 However, the crystal structure of HKUST-1 is changed by water molecules, and its surface area decreases.^30,31 To ensure the practical applications of HKUST-1, it is important to increase its resistance to water. To improve its stability to water, strategies such as incorporation of other materials, including graphite oxide³² and carboxyl-functionalized attapulgite,³³ have been developed. In the post-processing using plasma, the adsorption of water molecules on HKUST-1 is inhibited by introducing hydrophobic groups with perfluorohexane.³⁴ In another method, the adsorption of water molecules on unsaturated metal sites was prevented by irradiating the HKUST-1 with oxygen plasma.³⁵ In addition, to improve the water tolerance, reduction of Cu(ii) ions in HKUST-1 was also proposed.³⁶ However, in the above-mentioned methods, mixing of other materials or post-treatment steps was essential.In this work, we synthesized HKUST-1 containing Cu(i) by plasma in liquid; the method involved in situ plasma treatment during the synthesis activated also by plasma. Its resistance to water was compared with HKUST-1 synthesized by conventional methods such as heating or addition of triethylamine at room temperature.HKUST-1 was synthesized using the plasma generated by applying a bipolar pulse voltage to the electrode in an ethanol–water solution containing copper nitrate trihydrate and BTC (Fig. S1 and S2^†). Hereafter in this paper, the thus-synthesized HKUST-1 will be referred to as PL-HKUST-1. For comparison, HKUST-1 was synthesized by the conventional heating method and by the addition of triethylamine at room temperature,¹⁹ and the HKUST-1 formed are referred to as CH-HKUST-1 and RT-HKUST-1, respectively. The details of the synthetic methods are described in the ESI.^†All the samples were characterized by X-ray diffraction (XRD) and thermogravimetric analysis. The XRD patterns of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 are shown in Fig. 1. In all the cases, the characteristic diffraction peaks of HKUST-1 were identified, confirming the phase-pure formation of HKUST-1 samples irrespective of the synthetic method.^37,38 Thermogravimetric analysis of HKUST-1 revealed that the thermal stability of PL-HKUST-1 was similar to those of CH-HKUST-1 and RT-HKUST-1 (Fig. S3^†).Open in a separate windowFig. 1XRD patterns of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 before and after immersion in water. Fig. 2 shows the fluorescence (FL) spectra of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 upon excitation at 310 nm at room temperature. Note that a broad peak around 520 nm was observed only for PL-HKUST-1 and not for CH-HKUST-1 and RT-HKUST-1. Such a behavior has been previously reported for Cu(i) complexes and is attributed to the metal-to-ligand charge transfer (MLCT) from Cu(i) to an empty antibonding π* orbital of the ligand.^39–42 Thus, the FL spectrum indicates that a certain amount of Cu(i) is formed in PL-HKUST-1, which highly contrasted to CH-HKUST-1 and RT-HKUST-1.Open in a separate windowFig. 2FL spectra of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 (λ_ex = 310 nm).The existence of Cu(i) in PL-HKUST-1 was also confirmed by X-ray photoelectron spectroscopy (XPS). The XPS spectrum of PL-HKUST-1 showed peaks at 932.2 and 934.6 eV, assignable to Cu(i) and Cu(ii), respectively (Fig. S4^†).^43,44 Although the reduction to Cu(i) inevitably proceeded upon X-ray irradiation,⁴⁵ the concentration of Cu(i) in PL-HKUST-1 was apparently higher than those in CH-HKUST-1 and RT-HKUST-1, which was consistent with the FL spectra. The plasma has ample free electrons and ions, which can reduce metal ions via electrochemical reactions.⁴⁶ The temperature of the plasma in liquid could be as high as 1000–7000 K,²⁷ and the reduction of Cu(ii) to Cu(i) by heat might occur.⁴⁷To examine the water stability of the MOFs, HKUST-1 was immersed in water at room temperature for 12 h. The XRD patterns of the samples after immersion in water were compared with those of the as-synthesized samples. The water treatment resulted in the appearance of new peaks at 2θ ≈ 9.4°–9.7°, 10.1°, 11.1°, 17.3°, and 19.6° for CH-HKUST-1 and RT-HKUST-1 (Fig. 1). Notably, the XRD patterns of PL-HKUST-1 before and after immersion in water were identical, with no detectable changes.The effect of water treatment on the morphology of HKUST-1 was also investigated using scanning electron microscopy (SEM). Particles with octahedral shape were obtained by the plasma in liquid method, similar to those obtained by the conventional heating method (Fig. 3). After immersion in water, the formation of particles with a thread-like morphology was observed for CH-HKUST-1 and RT-HKUST-1, suggesting the decomposition of HKUST-1.^30,48 In contrast, although PL-HKUST-1 contained a portion of the etched corners, the particle shape and size remained unchanged after water treatment.Open in a separate windowFig. 3SEM images of (a and b) CH-HKUST-1, (c and d) RT-HKUST-1, and (e and f) PL-HKUST-1 before and after immersion in water.Fourier transform infrared (FTIR) spectra of HKUST-1 before and after the water treatment are shown in Fig. 4. All as-synthesized samples showed the typical characteristic peaks of HKUST-1. The bands from 1300 to 1700 cm⁻¹ are associated with the carboxylate group of the BTC ligand.⁴⁹ The two peaks in the range 1371–1448 cm⁻¹ correspond to the symmetric stretching vibrations of the carboxylate group.⁵⁰ The bands at 730 and 758 cm⁻¹ correspond to the in-plane C–H bending mode.⁴⁹ Peaks observed below 600 cm⁻¹ correspond to the bonds involving copper ions.⁴⁹ After immersion in water, the FTIR spectrum of PL-HKUST-1 did not show any significant change whereas those of CH-HKUST-1 and RT-HKUST-1 showed shifts in the peaks and formation of new peaks. When exposed to water, peaks corresponding to COO vibrations were observed for CH-HKUST-1 and RT-HKUST-1 between 1200 and 1700 cm⁻¹ due to a change in the environments of the linker BTC.⁴⁸ The peak around 1640 cm⁻¹ shifted to longer wavelengths, and a new peak appeared around 1570 cm⁻¹, which is consistent with previous research.³⁸ The Raman spectra of CH-HKUST-1 and RT-HKUST-1 also showed the structural change in the coordination bonding upon the water treatment (Fig. S5^†).⁵¹Open in a separate windowFig. 4FTIR spectra of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 before and after immersion in water. Fig. 5). The BET surface areas of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 were 888, 574, and 739 m² g⁻¹, respectively. After immersion in water, the amount adsorbed by CH-HKUST-1 and RT-HKUST-1 was lowered compared to that before immersion, and their BET surface areas were 407 and 351 m² g⁻¹, respectively. By contrast, in the case of PL-HKUST-1, the adsorption amount remained high even after immersion in water, and its BET surface area was 811 m² g⁻¹.Brunauer–Emmett–Teller surface areas of CH-HKUST-1, RT-HKUST-1, and PL-HKUST-1 before and after immersion in water

A concise and sequential synthesis of the nitroimidazooxazole based drug,Delamanid and related compounds

A concise, protection-group free and sequential route has been developed for the synthesis of the nitroimidazole based FDA-approved multi-drug resistant anti-tuberculosis drug, Delamanid and anti-leishmanial lead candidate VL-2098. The synthesis required chiral epoxides (11 and 17) as key intermediates. The chiral epoxide 11 was synthesised by sequential reaction cascades viz., allylation, selective N-arylation, Mitsunobu etherification, Sharpless asymmetric dihydroxylation and epoxidation, which do not require any special/dry reaction conditions. The steps involved towards the synthesis of epoxide also worked nicely in gram scales. After the synthesis of epoxide 11, the synthesis of Delamanid was achieved by reaction with 2-bromo-4-nitroimidazole 12 with an overall yield of 27%. Similarly, anti-leishmanial lead candidate VL-2098 was also synthesized in an overall yield of 36%.

A concise, protection-group free and sequential route has been developed for the synthesis of the nitroimidazole based FDA-approved multi-drug resistant anti-tuberculosis drug, Delamanid and anti-leishmanial lead candidate VL-2098.

Imidazoles are present in a wide variety of biologically relevant molecules exhibiting diverse pharmaceutical properties. Specifically, nitroimidazole containing compounds are active therapeutic agents against a wide variety of protozoan, bacterial (anaerobic) and leishmanial infections of humans and animals.¹ The notable examples of drugs are fexindazole,² metronidazole,³ benznidazole,⁴ tinidazole,⁵etc. Nitroimidazole was also well explored in the area of tuberculosis (TB) drug discovery (the structure of nitroimidazole containing drugs and lead compounds shown in Fig. 1).^6–9 CGI-17341 (I, developed by Ciba-Geigy, India) represents one of the very earliest outcomes but was not continued because of mutagenicity.⁶ Continued efforts to overcome the mutagenic liability led to the discovery of Delamanid (II, OPC-67683, a blockbuster against multi-drug resistant-TB, approved in 2014 by the EU)⁷ and Pretomanid^8a (III, PA-824, against multi-drug-resistant-MTB, approved in 2019 by the USFDA).¹⁰ Our involvement in the area of the TB drug discovery program and nitroimidazole chemistry^8b,c motivated us to develop a new concise and improved strategy towards the synthesis of Delamanid. The first synthesis of Delamanid was done by Tsubouchi et al. in 2004 (Otsuka Pharmaceutical Ltd. WO2004033463A1) which involved 16 steps (details shown in Fig. S1 of ESI^†).^11,12 The synthesis involves protection–deprotection strategy and made the process lengthy. Later on, in 2011, Otsuka had developed another concise route for Delamanid with improved yield (upper half of Fig. 2, details shown in Fig. S2 of ESI^†). This method involved the Sharpless epoxidation of 2-methyl allylalcohol followed by ring opening with 4-bromophenol. Then coupling with 4(4-trifluoromethoxy phenyl)piperidine fragment under palladium catalyzed conditions, which in turn was synthesized in 2–5 steps.¹³ Considering the importance of Delamanid, It could be better if more concise route was developed. In this regard, here we devised a route which involves sequential addition of fragments which not only avoid protection and deprotection but also provides the advantages of avoidance of dry conditions and costly intermediates. The lower half of Fig. 2 represents the strategy of the present method used for the synthesis of Delamanid, which involve the sequential coupling with following cascade viz., allylation, selective N-arylation, Mitsunobu ether formation, Sharpless dihydroxylation, epoxidation, ring opening and cyclization using inexpensive and easily available starting materials.Open in a separate windowFig. 1Nitroimidazole containing drugs and leads.Open in a separate windowFig. 2Previous and current approaches.The present synthesis started with 2-methylallyl chloride as first starting material and its selection is because of following reasons (i) as protecting group, (ii) inexpensive (33$ per 100 mL, Sigma) in comparison to 2-methylallyl alcohol (766$ per 100 mL, Sigma) which is used in earlier reported method and (iii) provide double bond functionality to generate epoxide via Sharpless dihydroxylation approach, which operates under open atmosphere conditions and avoids the anhydrous and dry environment as required for Sharpless epoxidation, used in the previous reported methods.^7,11b,12     

Three-component assembly of stabilized fluorescent isoindoles

The tandem addition of an amine and a thiol to an aromatic dialdehyde engages a selective three-component assembly of a fluorescent isoindole. While an attractive approach for diversity-based fluorophore discovery, isoindoles are typically unstable and present considerable challenges for their practical utility. We found that introduction of electron-withdrawing substituents into the dialdehyde component affords stable isoindole products in one step with acceptable yields and high purity.

The tandem addition of an amine and a thiol to an aromatic dialdehyde engages a selective three-component assembly of a stabilized fluorescent isoindole.

Since the preparation of the first isoindole (1, Fig. 1) in 1951 (ref. 1) and the isolation of the parent unsubstituted isoindole (2) in 1972,² the relative instability of this heterocyclic ring system has been an important impediment to the discovery of new chemical transformations and biological applications. The position of the equilibrium between the two tautomeric forms 2 and 3, respectively 2H- and 1H-isoindoles, could be invoked to assess the stability of the 2H-form. It has been found that substituents on the isoindole ring system play a key role. For example, it appears that electron-donating groups, such as methyl groups in 4, destabilize the 2H-isoindole,³ whereas electron acceptors in 5⁴ and 6⁵ improve stability.Open in a separate windowFig. 1 N-methylisoindole (1) and a selection of the first isoindoles prepared 4–6 along with a depiction of the substituent-based tautomeric preferences.Multicomponent reactions^6,7 that enable three or more discrete molecules to combine into one product not only curtail synthetic operations but also advance the complexity viable within a single operation. To date, many of our fluorescent probes are prepared by two-component processes wherein moiety A is attached to moiety B to generate a fluorescent probe. Conventionally, this is achieved by adding dye A to a biological molecule B, however methods have been established that generate the probe motif as part of the coupling process.^8,9 The latter, referred to as turn-on labeling, advantageously removes potential non-fluorescent impurities as only the desired product displays the proper fluorescence. While rare, advance of multicomponent turn-on labeling strategies offers a robust ability to improve the selectivity of labeling as well as to further expand the diversity possible within a labeling reaction. Here, we turn our attention to explore a three-component strategy to prepare isoindoles with improved stability.An early report of the formation of fluorescent species when o-diacetylbenzene was exposed to proteins¹⁰ led to the discovery of a multicomponent reaction between o-phthalaldehyde (7), amines 8 and thiols 9, which yields highly fluorescent isoindole 10 (Fig. 2).^11–16 This reaction now forms the basis for the quantitative determination of amino acids and is used in commercial amino acid analyzers.¹⁷ The method is characterized by high sensitivity, although the lack of mechanistic understanding has led researchers to optimize the conditions primarily empirically.Open in a separate windowFig. 2The three-component isoindole reaction. (a) Reaction of phthalaldehyde (7) or 2,3-naphthalenedicarboxaldehyde (11) with amines (8) and thiols (9) to afford fluorescent isoindoles 10 and 12, respectively. (b) Proposed mechanism of the reaction with 7 where the initial formation of imine 7a is followed by an attack by a thiol 9 to form acetal-like species 7b. This undergoes cyclization to give hemiaminal 7c with a subsequent elimination of water to result in isoindole 10.An important drawback of the method is the lack of stability of the product isoindoles 10 (Fig. 2), which, once form, undergo further conversions introducing inaccuracies due to unstable fluorescence. In general, the highest fluorescence must be achieved within 5–25 min and remain time-independent for another 20–30 min, the conditions which are hard to fulfill as the rate of isoindole formation and its stability depend on an individual amino acid.^18,19 Naphthalene-1,2-dicarboxaldehyde (11) was recommended as an alternative reagent with claims that the product isoindoles 12 would be more stable, but the proposal seemingly has not received acceptance from the scientific community as the increases in stability are probably not significant to justify the cost of this reagent.¹⁷Our initial attempt to characterize the product of the three-component reaction between phthalaldehyde 7, amines and thiols (Fig. 3) met with significant synthetic challenges, as evident by the low stability of 10a. This compound is unstable at room temperature and rapidly decomposed when column chromatography purification was attempted. In order to obtain an analytical sample, 10a was repeatedly recrystallized from cold CH₃CN, dried in vacuum at 0 °C and immediately analyzed by NMR. Isoindole 12a, derived from 2,3-naphthalenedicarboxaldehyde (11), turned out to be only slightly more stable in comparison to product 10a and also rapidly decomposed when column chromatography purification was attempted.Open in a separate windowFig. 3One-pot synthesis of fluorescent 1-thio-2H-isoindoles and related structures from aromatic dialdehydes, butylamine and N-(tert-butoxycarbonyl)-l-cysteine methyl ester (Boc-Cys-OMe).Electron-deficient dialdehydes 13, 15, 17 and 19 (Fig. 3) on the other hand, all gave stable isoindoles 14a, 16a (structure assigned by NOESY analyses, see ESI^†), 18a and 20a respectively (Fig. 3), when reacted with butyl amine and protected cysteine. These isoindoles could be purified by column chromatography and were considerably easier to handle.Next, we turned our attention to evaluate if n-butyl- and n-octylphthalimidic phthalaldehydes 17 and 19 produced readily isolated products from a variety of aliphatic or aromatic amines and thiols. As shown in Fig. 4, isoindoles 18b–d and 20b–f can be obtained by adding a thiol and amine to the solution of 17 or 19 in CH₃CN at 0 °C. Subsequent simple removal of the volatiles on the rotary evaporator and purification of the product, facilitated by its fluorescence on TLC, gave the desired 18b–d and 20b–f in a straightforward manner. These reactions could be conducted with a 1 : 1 : 1 ratio of dialdehyde, amine, and thiol in acceptable isolated yields (48–66%, Fig. 4). The yields did not seem to be affected by the electronic properties of the reacting amines or thiols and were similar for reactions involving electron-rich (18b, c, 20c–f) vs. electron-deficient (18d, 20b) amines or electron-rich (18c, 20d) vs. electron-deficient (18b, d, 20b, c, e, f) thiols.Open in a separate windowFig. 4One-pot synthesis of fluorescent 1-thio-2H-isoindoles from n-butyl- and n-octylphthalimidic phthalaldehydes 17 and 19, aliphatic and aromatic amines, and aliphatic and aromatic thiols.While an attractive analytical tool and fluorophore, practical applications of isoindoles suffer due to their rapid degradation. Proposed early on by Simons and Johnson,²⁰ the problem arises from nucleophilic attack by ROH (water or alcohols) at C1 (Fig. 5) resulting in the loss of the thiol and formation of the corresponding γ-lactam 21b.²¹ This is further complicated by the potential for self-dimerization by a Diels–Alder reaction as well as cycloaddition with oxygen, the latter of which results in the incipient formation of a rapidly degraded endoperoxide. In 1981, a team led by Simmons and Ammon reported the first stable isoindole by the reaction with dimethylene acetylenedicarboxylate.²² Here, the product of the Diels–Alder cycloaddition opened to deliver a stabilized isoindole by indirect functionalization at C3. While a practical discovery, the overall analytical utility of isoindoles would benefit from discovery of a material with bench stability.Open in a separate windowFig. 5Stability analyses on isoindole 18b were evaluated using time course NMR studies. Selected spectra are shown with expansion of the aromatic region from 6.50–8.50 ppm. The predominant product of this degradation step found to be 21b. Expansions and spectra from treating 18a, 18c and 18d under the same conditions are provided in the ESI.^†Overall, we were able to prepare and collect spectral data on 13 new isoindoles (Fig. 3 and ​and4).4). These materials were sufficiently stable for purification and spectral analyses. While we were able to prepare and isolate 10a and 12a, spectra on these materials needed to be collected immediately after preparation. NMR analyses were most challenging due to the fact that trace acidic or basic materials in the solvents led to rapid decomposition ultimately leading to the use of acetone-d₆ for NMR data collection.To further evaluate their utility, samples of 18a–d were monitored for their stability neat and in solution. Subjecting these samples to the same protocol (see ESI^†), isoindoles 18c and 18d were not sufficiently stable in neat form to endure >30 days at −20 °C followed by 48 h at 23 °C (conditions that modelled compound storage). Under the same conditions, 18a and 18b (Fig. 5a) were stable when stored (>30 days at −20 °C followed by 48 h at 23 °C) and when dissolved acetone-d₆ (Fig. 5a) and kept in the dark (Fig. 5b). Exposure to light, however, led to decomposition of both 18a and 18b (Fig. 5c). These observations indicated that steric bulk within the amine and thiol components contributed to the products stability. Additionally, the presence of alkene functionality within the amine was not tolerated, as given by the comparison of unstable 18d to stable 18a.Synthesis of isoindoles²³ through a three-component coupling provides a robust tool to rapidly access diverse fluorescent materials as recently demonstrated by adaptation for a Click-like processes²⁴ or crosslinking,²⁵ called Flick. Here, we describe how the addition of electron withdrawing groups effectively stabilizes the materials as demonstrated by 18a and 18b. While this data suggests that stability can be achieved, the light sensitivity of these agents suggests a future potential as photochemical sensors or modifiers. Efforts are now underway to explore this application.     

Thermally induced fragmentation of nanoscale calcite

Calcite nanorods ∼50 nm wide are thermally separated into nanoblocks. The fragmentation is ascribed to the ion diffusion on metastable crystal surfaces at temperatures (∼400 °C) much lower than the melting point. The presence of water molecules enhances the surface diffusion and induces deformation of the nanorods even at ∼60 °C.

Calcite nanorods ∼50 nm wide are thermally separated into nanoblocks.

Calcium carbonate is a common industrial material that is used as a micrometric filler for papers, rubbers, plastics, and inks. The shape and size of micrometric grains are important parameters that affect the physical and chemical properties of composite materials.^1–5 In recent years, nanometric particles of calcium carbonate have attracted much attention as basal building blocks of biogenic minerals^6–10 and functional materials with high biocompatibility and low environmental load.^11–14 Since various properties are influenced by the miniaturization of crystal grains below 100 nm, characterization of the carbonate particles is necessary for application in practical fields. However, their properties, including the thermal characteristics of nanometric calcium carbonate in the nanometric region, have not been sufficiently clarified because calcium carbonate is easily decomposed above 550 °C.^15,16 In the present work, we studied thermally induced deformation on nanometric calcite at temperatures lower than the melting point (1597 °C at 3 GPa)¹⁷ of the bulky crystal.Since the melting temperature of metals decreases when their size is decreased below ∼50 nm,^18,19 metallic nanowires fragment into nanospheres at temperatures much below the melting point of bulk metal.^20–22 The fragmentation is ascribed to the Rayleigh instability that is known for liquid. These results suggest that the surface diffusion of ions and atoms occurs easily on the nanometric particles when the surface instability is increased. The cleavage of solid nanowires has been observed only for metallic phases. In the current work, we found the morphological transformation of ion crystal nanorods into faceted nanograins through the surface diffusion at relatively low temperatures.The preparation of bulky calcium carbonate consisting of nanocrystals is required for reinforcing materials^23–25 and as a precursor of biomedical materials.^26,27 In general, however, fabricating large, bulky bodies through conventional sintering techniques is difficult because calcium carbonate is thermally decomposed into calcium oxide and carbon dioxide. Several methods, such as sintering with a flux^16,28 or in a carbon dioxide atmosphere²⁹ and hot-pressing under hydrothermal conditions^30,31 were developed to prepare bulky calcium carbonate materials. On the other hand, the thermal behaviors of pure calcium carbonate have not been sufficiently studied at temperatures below the decomposition and melting points.In nature, bulky calcium carbonate crystals are commonly produced as biominerals, such as shells, eggshells, sea urchins, and foraminiferal skeletons, under mild conditions.^{3,9,10,32–34} The bulky biogenic bodies are composed of nanometric grains 10–100 nm in size that are arranged in the same crystallographic direction.³ The formation of bridged architectures through oriented attachment is generally related to the ion diffusion on specific surfaces at relatively low temperatures. A detailed study on the stability of nanometric surfaces at relatively low temperatures is needed to understand the morphological change of calcium carbonate crystals.In the present report, we discuss the morphological change of calcite nanocrystals below the decomposition and melting temperatures by observing metastable crystal surfaces in the nanometer-scale range. Calcite nanorods elongated in the c direction were utilized as a typical nanometric shape covered with metastable surfaces. Here, thermally induced fragmentation was studied with and without water vapor. The surface diffusion was found to occur on the metastable surface at around 400 °C under a dry condition and at around 60 °C with water vapor. Our findings are important for clarification of the surface property of nanometric calcium carbonate and for the fabrication of bulky bodies through the attachment of nanocrystals.Single-crystal calcite nanorods elongated in the c direction were utilized in the present study (Fig. 1 and S1^†). Calcite nanorods up to ∼500 nm were formed through the combination of the carbonation of calcium hydroxide and the subsequent oriented attachment of resultant calcite nanoblocks ∼50 nm in diameter by stirring. The detailed mechanism was described in our previous study.³⁵ As shown in Fig. S1,^† the calcite nanorods were covered with metastable surfaces having a curvature. Moreover, we observed depressed parts originating from the oriented attachment of the original calcite grains. As shown in the Fig. S2,^† the XRD peaks of the nanorods were found to shift to higher angles than those of standard X-ray diffraction data (ICDD 00-005-0586). Thus, the crystal lattice of the nanorods was suggested to be stressed with the coverage of irregular surfaces.Open in a separate windowFig. 1SEM (a) and TEM (b and c₁), HRTEM (c₂) images, and the FFT pattern (c₃) of the lattice in (c₂) of calcite nanorods in aqueous dispersions at pH 12 and at 25 °C with stirring. (c) Reprinted from ref. 35 published by The Royal Society of Chemistry.As shown in Fig. 2, the calcite nanorods were deposited on a silicon substrate for clear observation of the morphological change. We redispersed the calcite nanorods in ethanol and evaporated the dispersion medium to deposit them on the substrate at 25 °C (Fig. 2a and S3a^†).³⁶ The nanorods were arranged on the solid surface through evaporation-driven self-assembly. Specifically, monolayers of the calcite nanorods were obtained by adding poly(acrylic acid) (PAA, MW: 5000 gmol⁻¹) to the ethanol dispersion. The dispersibility of the nanorods in ethanol was improved by the modifying agent. The organic components of the PAA-modified nanorods were removed through oxidation in air at around 300 °C (Fig. S4^†).Open in a separate windowFig. 2SEM images and schematic illustrations of calcite nanorods deposited on a silicon substrate before treatment (a) and heated at 400 °C for 1 (b) and 2 h (c). The PAA-modified calcite nanorods were used to obtain the monolayers (b and c). We used bare nanorods for take the images of original nanorods because the definite surfaces were not observed due to the presence of PAA (a).The calcite nanorods were deposited on the solid surface to study the morphological change when heated in air. Obvious changes were not found in the shape of the nanorods upon heating to a temperature below 350 °C in air for 24 h (Fig. S2^†). On the other hand, we observed significant deformation upon heating to 400 °C (Fig. 2). The depressed parts on the side surfaces enlarged in 1 h. The fragmentation of the nanorods was finally induced after treatment for 2 h. Calcite grains were formed by the thermally induced cleavage (Fig. 2c). The average size of the cleaved grains was ∼100 nm, which was larger than the average width of the nanorods, ∼50 nm. As shown in Fig. 3, we observed the definite surfaces covering nanograins. Most of the definite facets were assigned to the (104) of calcite by FFT analysis of the lattice fringes of nanograins in the HRTEM images. Some (012) planes were found in the nanograins. On the other hand, the surfaces of the deformed nanorods during fragmentation were curved and irregular. According to XRD patterns, the crystal phase was not changed with the fragmentation (Fig. S2^†). The diffraction peaks were shifted to the standard values and sharpened with the treatments. This suggests that the formation of the stable faces with the fragmentation is associated with the lattice relaxation.Open in a separate windowFig. 3TEM (a), HRTEM (b), and FFT images of nanocrystals before and after heating at 500 °C.We observed the stability of rhombohedral grains that were covered with the stable {104} planes. As shown in Fig. 4, the deformation of the rhombohedral grains was not observed at 400 °C in air for 6 h. These results indicate that the ion diffusion is not induced drastically on the stable surfaces at a temperature lower than the decomposition temperature.Open in a separate windowFig. 4SEM (a_1,2 and b_1,2), TEM (a₃), and SAED (a₄) images of calcite nanoblocks before treatment (a) and heated to 400 °C for 6 h (b). (a₃) A schematic illustration of a calcite rhombohedron covered with {104} faces.The fragmentation of the calcite nanorods was enhanced in the presence of water vapor. As shown in Fig. 5a, we found cleavage of the nanorods even at 60 °C in a closed vessel containing water. The formation of unifaceted rhombohedral nanoblocks with {104} faces was clearly observed at 100 °C for 24 h (Fig. 5b–d). Since the morphological change was similar to that under a dry condition, the ion diffusion on the surface is deduced to be assisted by adsorbed water molecules. The X-ray diffraction signals shifted to the standard values with the fragmentation (Fig. S2^†). Thus, the stable faces were formed with the lattice relaxation with the exposure to water vapor.Open in a separate windowFig. 5SEM (a and b), TEM (c), and SAED (d) images of calcite nanorods deposited on a silicon substrate subjected to high humidity at 60 °C (a) and 100 °C (b) for 24 h. (c) A schematic illustration of a calcite rhombohedron covered with {104} faces.The ion diffusion at a relatively low temperature, below the decomposition temperature, has not been reported for calcium carbonate. In the present work, however, we found the fragmentation of calcite nanorods at around 400 °C under a dry condition and at around 60 °C with water molecules. These results suggest that the ion diffusion occurs on the nanoscale calcite crystals. On the other hand, rhombohedral calcite grains covered with the stable {104} planes were not deformed at those temperatures. Thus, the diffusion at low temperatures is induced only on metastable surfaces that are exhibited on the nanoscale calcite. Moreover, the presence of water molecules enhances the ion diffusion on the metastable surfaces.The fragmentation of the calcite nanorods can be explained by Rayleigh instability. The cleavage by Rayleigh instability is ascribed to the enlargement of tiny perturbations on cylindrical liquids,³⁷ polymers, and metals. In general, the cylindrical bodies evolve into several spheres to decrease the total surface energy. Recently, Rayleigh instability was applied to the thermally induced fragmentation of metal^20–22 and organic³⁸ nanowires. The breakup phenomena were attributed to surface oscillations due to the high surface energy induced by increased surface-to-volume ratios.³⁹ Thus, metal nanowires are cleaved and form isotropic nanoblocks at temperatures well below the melting point. In the present work, we found fragmentation of the calcite nanorods at relatively low temperatures. The ion diffusion is induced on the metastable surfaces that are exhibited on nanoscale crystals. The depressed parts exist as perturbations on the side faces of the original nanorods. The cleavage occurs through enlargement of the depressed parts and formation of the stable faces to reduce the surface energy and relax the lattice strain.Polyhedral grains covered with flat planes were formed instead of spherical particles by the fragmentation of calcite nanorods. Formation of the stable {104} plane is achieved to reduce the surface energy. The {012} plane of calcite is not stable under the ambient temperature. However, the surface energy of {012} decreases with increasing temperature.⁴⁰ Thus, the facets are deduced to also be formed at temperatures around 400 °C.     

Effect of electric field on the electrical properties of a self-assembled perylene bisimide

A functionalised perylene bisimide forms two different self-assembled structures in water depending on the solution pH. Structure 1 (formed at pH 6.2) consists of a fibrous structure, whilst structure 2 (formed at pH 9.4) consists of disordered aggregates. Despite being formed from the same molecule, structure 1 shows higher stability under illumination and electric field than structure 2, demonstrating that the nature of the self-assembled aggregate is critical in devices. Interestingly, both structures show p-type behaviour.

A functionalised perylene bisimide forms two different self-assembled structures in water depending on the solution pH.

Conjugated small molecules have shown promising results in optoelectronic devices such as photovoltaics (PVs),¹ field effect transistors (FETs),^2,3 light emitting diodes (LEDs),⁴ and photodetectors.⁵ Perylene bisimides (PBIs, also called perylene diimides) are well-known electron transporting/accepting n-type organic semiconductors for optoelectronic devices.^6,7 PBIs could show high electron conductivity and are the best non-fullerene n-type materials for organic photovoltaic applications.⁸ These materials also have high extinction coefficients, high thermal and chemical stability, and chemical tunability.^9,10PBIs can be used to form useful FETs with high electrical conductivity. The change of electrical properties of PBI is due to the different stacking of the molecules which is influenced by the structure, solvent and concentration used to self-assemble the PBIs. For example, N,N′-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDIF-CN₂) forms large grains upon post-thermal annealing of a spin-coated film at 110 °C under vacuum, resulting in efficient n-type channel field effect transistor.¹¹ Jones et al. prepared efficient air-stable n-type FETs based on a core-cyanated PBI derivative.¹² They showed a significantly higher conductivity for the thermally evaporated PBI derivative in a top contact configuration, while substantial drop of conductivity observed for the solution-processed PBI-based FET for a bottom gate structure.The formation of controlled crystalline structures of PBIs to achieve high charge carrier mobility is difficult. Where the self-assembly can be controlled, this can lead to enhancement of their electrical conduction. Oh et al. observed solution based thin film formation of a PBI derivative in an OFET structure.¹³ The OFET device showed field effect n-type property with good electrical conductivity as a result of the slip-stacked face-to-face molecular packing of the PBI molecules and their dense parallel arrangement. Another study reported a liquid crystal (LC) PBI with space-charge limited current shows higher conductivity under ambient conditions.¹⁴ These LC PBIs form one-dimensional columnar stacks with intermolecular π–π orbital overlap to enhance mobility. Theoretical work reported by Delgado et al. showed the change of electron and hole conductivity upon addition of different end-substituted and core-substituted groups to a PBI.¹⁵ The change is due to different structural forms of the PBI.PBIs structure are intrinsically insoluble and mostly used as fluorescent dyes with high fluorescent quantum yield. These materials are however well-known for their excellent n-type behaviour for different optoelectronic devices such as solar cells and field effect transistors (FETs). Water-based PBIs are promising for biofriendly optoelectronic device application with the possibility of PBI thin film formation in PVs and FETs. However, there is limited information in the literature regarding the lateral field effect conductivity of water-based perylene structure in a FET configuration at dark and under illumination.PBIs in general can form a range of supramolecular structures, which depend on different types of intermolecular forces such as hydrogen bonding, π–π stacking and metal–ligand interactions.¹⁰ Among these non-covalent interactions, π–π stacking plays an important role in self-assembly of PBI derivative in both solution and films.^16,17 The dynamics of the supramolecular structure can be controlled via different conditions such as the pH, temperature and concentration. PBIs can form either H- or J-type aggregates,^18–20 although we and others have recently highlighted that this assignment needs to be completed with great care.^21,22We have been working with a series of amino acid functionalised PBIs. These have the advantage of being water-soluble, and we have shown that it is possible to control the aggregation type and electronic behaviour by varying the amino acid substituents.²³ The chemical structure of the water-soluble alanine-appended PBI (PBI-A) studied in this work is shown in Fig. 1. The aggregation of PBI-A in water is driven by the hydrophobicity of the PBI core in the aqueous environment. The structures formed depend on the pH of the solution. We have previously shown for this molecule that worm-like micelles are formed at a pH of less than 7, with gels being formed by a transition to fibres below a pK_a of 5.4.²⁴ The control of self-assembled structure formation of PBI-A film along with its promising photoconductivity^25,26 makes it as an interesting candidate for the next generation semiconductor devices. Previously, we have focussed on preparing films from PBI-A in the mono-deprotonated state. Here, we specifically compare films prepared from PBI-A at two different solution pH. The degree of deprotonation is different at these two pH values, which affects the aggregation and self-assembly. We show that this directly affects the film quality. We also show that this n-type semiconductor can show p-type behaviour.Open in a separate windowFig. 1(a) Chemical structure of the alanine-functionalised perylene bisimide (PBI-A) as singly deprotonated (1) and doubly deprotonated (2) forms. (b) Photographs of solutions of the PBI at pH 6.2 (b, forming structure 1) and at pH 9.4 (c, forming structure 2). The black scale bar indicates 1 cm.PBI-A was synthesised as described previously.²⁷ This molecule has two apparent pK_a.²⁴ The PBI can be dispersed in water by raising the pH above the lowest pK_a of the molecule. This can be achieved by using a single equivalent of a base (formally to deprotonate a single carboxylic acid), or with two equivalents of base to form the doubly deprotonated species. Solutions of PBI-A were prepared at a concentration of 5 mg mL⁻¹. On adding a single equivalent of base, the pH of this solution was 6.2. Slightly viscous solutions with a shear-thinning behaviour were formed (Fig. 1b) as can be seen the viscosity measurements (Fig. S1, ESI^†). Shear thinning can be assigned to the presence of worm-like micelles as they align at high shear rates.²⁴ Films can be formed from these solutions by simply drying on a surface. Long, anisotropic structures are present after drying, as shown by SEM (Fig. 2a). We refer to these as structure 1 throughout this report.Open in a separate windowFig. 2SEM images of PBI-A for (a) structure 1 and (b) structure 2 as formed by drying on a silicon substrate. The scale bar represents 500 nm in both cases.Adding two equivalents of base results in a solution at pH 9.4. The doubly deprotonated PBI-A does not self-assemble into defined structures, resulting in a lower viscosity (Fig. S1, ESI^†). We have shown previously by small angle scattering that there is limited self-assembly under these conditions.²⁸ On drying, ill-defined aggregates are formed, which we refer to as structure 2 (Fig. 2b). The differences between structures 1 and 2 arise from the charge on the PBI-A, with the 2 being more negatively charged and so more soluble in water, and 1 being less charged and therefore more hydrophobic. There are slight differences in the film morphologies for both structures compared to our previous reports; this is due to us using hydrophilic surfaces here whilst our previous data used hydrophobic surfaces (comparative data are shown in Fig. S2, ESI^†).UV-Vis absorption and photoluminescence (PL) spectra of films formed from both structures are shown in Fig. 3. The absorption spectra of both films are similar, with a slightly stronger 0–0/0–1 vibronic band ratio for structure 2 as compared to 1. The different ratio of the peaks indicates different molecular packing in the structures.^9,21Open in a separate windowFig. 3Normalised UV-Vis absorption (solid lines) to absorption peak at 505 nm and normalised PL intensity to the emission peak at 674 nm (dashed lines) for PBI-A film excited at 500 nm for structure 1 (black data) and (b) structure 2 (red data).The PL spectra for both films (excited at 500 nm) appear similar with a more resolved shoulder at longer wavelength for structure 2, which is due to the stronger 0–0 vibronic band absorption. The non-normalised PL spectra with maximum absorption for two structures are compared in Fig. S3 (ESI^†). The maximum PL peak is quenched significantly for structure 1 in comparison with structure 2. This substantial decrease in PL intensity peak can be explained as a result of fibre formation in structure 1 and a better charge separation upon photoexcitation. For structure 2, the stronger PL is an indication of amorphous structure and consequently more exciton quenching.We prepared devices with either structure 1 or structure 2 as the active layer. The fabrication procedure for our devices is shown as a schematic diagram in Fig. 4. Briefly, p-doped Si coated by 300 nm SiO₂ was used as a substrate and a FET device with bottom gate top contact architecture is fabricated. A PBI-A film with either structure 1 or structure 2 acted as the active layer. Gold contacts with 25 nm thicknesses were evaporated as the top source and drain contacts via thermal evaporation system. Using these devices, we examined the effect of electric field on the photoconductivity and structure of films comprised of either structure 1 or 2. The electrical properties of these two structures are compared in the dark and UV light illumination under different applied electric fields.Open in a separate windowFig. 4Schematic of device fabrication procedure: (a) p-doped silicon/SiO₂, (b) ultrasonic bath in acetone and isopropanol each for 10 minutes, (c) oxygen plasma treatment at 50% power for 10 seconds, (d) drop-casting PBI-A solution on top of SiO₂ and (e) evaporation of 25 nm gold as a source and drain contact.The electrical conductivity of both structures was measured in the dark, and under irradiation with 365 nm light at different gate applied positive voltages of between −40 to 50 V (Fig. 5). Illumination with this wavelength was chosen on the basis of our previous reports.⁹ We observe an increase in conductivity under UV illumination, which is in agreement with our previous work^9,21,29 and for related PBIs by other groups.²⁵ This is due to the formation of radical anions and dianions, which are long-lived charged species under UV illumination and enhance the conductivity of PBI-A film.^9,30,31 The device formed using structure 1 shows a substantial source-drain current from 160 nA in dark to 20.4 μA under UV illumination. These currents are under −40 V gate bias voltage. A weak p-type behaviour is observed for both dark and light currents. The source-drain current in dark decreases from 160 nA at −40 V to 37.5 nA at 50 V. Under 365 nm illumination, the currents for structure 1 changes from 20.4 μA at −40 V to 19 μA at 50 V. As a result, the p-type field effect transistor for structure 1 is stronger in the dark (Fig. 5a).Open in a separate windowFig. 5Source-drain current versus gate voltage for PBI-A film with (a) structure 1 and (b) structure 2 in the dark (black line) and illuminated with 365 nm light (red line).For devices formed using structure 2, the conductivity in both the dark and under illumination also showed weak p-type behaviour. The dark current drops from 135 nA at −40 V to 80 nA at 50 V gate voltage. The conductivity under 365 nm illumination changes from 500 nA at −40 V to 200 nA at 50 V. Structure 2 shows the same p-type behaviour in both dark and under illumination as shown in Fig. 5b. This is similar to the effect observed by Besar et al. in OFET devices based on quaterthiophene core and the assembled peptide forming 1D nanostructures. The high off current between source-drain is due to the significant ionic current in the material due to the amino acid groups.³⁰To explain the better conductivity of structure 1 compared to structure 2, we investigated the films in the dark under an applied electric field and after the simultaneous irradiation and an applied electric field. To irradiate the films, we used a 365 nm LED as we have previously shown that there is a significant enhancement of the conductivity of a film of structure 1 under this wavelength.^9,21,29 Under an applied electric field (gate) through the film in the dark, structure 1 does not show any significant morphological change (compare Fig. 6a with the structure shown in Fig. 2a). On application of an electric field and the LED, the films change morphology, but continuous domains can still be seen; the film shows the presence of significantly smaller fibres compared to before the application of the field and LED. These are however still connected to each other. Whilst we are unaware of other examples of changes in PBI films on application of an electric field, it is well known that electromechanical forces can cause changes in other systems.^32,33Open in a separate windowFig. 6SEM image of films formed from (a) structure 1 at dark and after applied electric field; (b) structure 1 after UV and applied electric field; (c) structure 2 at dark and after applied electric field; (d) structure 2 after UV and applied electric field.In comparison, application of the electric field to structure 2 results in the domains becoming smaller (compare Fig. 6c with ​with2b).2b). The film of structure 2 under the applied electric field in the dark (Fig. 6c) shows structures with more dispersed white bright objects. As observed in the SEM image in Fig. 6d, these white features become less dispersed over the film after illumination and an applied electric field. The presence of these features could be due to the presence of sodium salts formed in structure 2. However, powder X-ray diffraction (pXRD) measurements (Fig. S4, ESI^†) of films of both structure 1 and structure 2 are similar and show no peaks which could be ascribed to sodium salts. Hence, the lower film conductivity and current stability can be explained by the formation of more disordered, small aggregated domains, which importantly are not making a continuous pathway between two electrodes.The field effect transistors based on both structure 1 and 2 show p-type behaviour in a bottom gate top contact configuration. This behaviour is not expected, as PBI is known to be an n-type material due to high electron affinity of the perylene core of PBI.^11,12 In a recent study presented by Draper et al., PBI-A showed an ionisation potential of −5.72 eV and an electron affinity of −3.91 eV.²³ Additionally, we have significant evidence for n-type behaviour of this molecule.^23,24 As such, the reason for the observed p-type behaviour here is unclear. A weak p-type behaviour of a peptide-functionalised, self-assembled PBI was previously observed by Eakins et al.³⁴ Silberbush et al.³⁵ found a substantial increase of hole transport of a peptide fibril network under various relative humidity conditions. Hence, this p-type behaviour might be due to the role of the amino acid (or peptide in the case of Eakins et al.²⁷), or the existence of ions in the film, which modulate charge injection, and transport in PBI. Alternatively, as discussed by Delgado et al.,¹⁵ the presence of functional group in a PBI can result in a lowering of the re-organisational energy of holes and consequently improved hole conductivity. It may be that the molecular packing on drying on the surfaces here leads to suitable morphological changes that favour p-type behaviour. Finally, we note that recent work by Zhang et al. have suggested that PBI films can show either p-type or n-type behaviour depending on the ratio of dianion to radical anion in the film.³⁶ This behaviour is the subject of further investigation.In conclusion, a water-dispersible perylene bisimide can form different structures depending upon the absolute solution pH. In a bottom gate top contact FET configuration, this material shows p-type behaviour with a substantial increase of current under 365 nm UV illumination. The ambipolar behaviour of water-based perylene bisimide derivative under different processing conditions may provide a route toward developing ambipolar FET devices based on the single material.     

Photoelectrochemical photocurrent switching effect on a pristine anodized Ti/TiO2 system as a platform for chemical logic devices

We report here the effect of the photoelectrochemical photocurrent switching (PEPS) observed on highly-ordered pristine anodized Ti/TiO₂ for the first time. At negative potential bias, blue irradiation gives cathodic photocurrent, whereas anodic photocurrent was observed for ultraviolet irradiation. We believe this phenomenon is due to the electron pathway provided by Ti³⁺ defect states.

We report here the effect of the photoelectrochemical photocurrent switching (PEPS) observed on highly-ordered pristine anodized Ti/TiO₂ for the first time.

Titanium dioxide, being one of the most studied materials, still draws much attention from researchers.^1,2 It is considered to be a very promising material due to its high chemical stability, nontoxicity, and its unique properties. Due to stable and robust photoactivity, titania is widely used in the design of solar cells³ and photocatalytic applications.⁴ In addition to the fact that titanium dioxide occurs in several crystalline modifications, it can also be obtained in various forms, such as, for example, nanotubes,⁵ nanofibers,⁶ and nanosheets.⁷ The photocatalytic performance of TiO₂ is highly dependent on crystallinity,⁸ phase content, form, and preparation method.⁹ It was reported that highly ordered arrays of TiO₂ nanotubes are characterized by short charge transport distance and little carrier transport loss.⁵ Therefore, electrochemically fabricated TiO₂ nanotube arrays are preferable compared to random non-oriented titania.¹⁰ Great varieties of photoelectrochemical behaviour can be achieved by doping¹¹ and surface modification.^12,13An interesting feature has recently been demonstrated for highly ordered arrays of TiO₂ nanotubes obtained by double stepwise electrochemical anodization of a titanium foil (Ti/TiO₂). Together with our colleagues observed that localized illumination of Ti/TiO₂ surface in water solution triggers proton flux from irradiated area.¹⁴ The photocatalytic activity of TiO₂ is based on photogenerated electron–hole pairs. Under the electric field of Ti/TiO₂ Schottky junction and due to upward surface band bending, efficient spatial charge separation occurs, and photoexcited holes (h⁺) reach TiO₂ – solution interface. The h⁺, which is a strong oxidizing agent, can react with water, and a pronounced pH gradient arises due to water photolysis. Thus, titanium dioxide can be used to trigger local ion fluxes, and proton release is associated with anodic photocurrent. The use of the light-pH coupling effect to control pH-sensitive soft matter was previously demonstrated.^15,16 Complementary species, H⁺ and OH⁻, annihilating when occurring simultaneously, extend chemical arithmetic with subtraction operation opening way to pure chemical calculations.¹⁷ Ion fluxes consideration as information transducers in solution were proposed¹⁸ and performing simple logic operations was demonstrated.¹⁹ This phenomenon opens perspectives to biomimetic information processing and developing effective human–machine interfaces.²⁰Photoelectrodes using light and potential as inputs and yielding photocurrents are being considered as the basis for logic devices. In this way, optical computing compatible with existing silicon-based devices may be performed.Logic operations are described by Boolean algebra operating with truth values denoted 0 (false) and 1 (true). Elementary logical operations are modelled by logic gates producing single binary output from multiple binary inputs and physically implemented by some switch. As for photoelectrode based information processing, the photoelectrochemical photocurrent switching (PEPS) effect is utilized. This effect is that under appropriate external polarization or/and illumination by light with appropriate photon energy, switching between anodic and cathodic photocurrent may be observed for n-type semiconductors and the opposite for p-type.^21,22Without further modification, this effect was observed for a very limited number of materials, such as bismuth orthovanadate, lead molybdate, V–VI–VII semiconductors, and some others. To show this effect, the majority of semiconductors require electronic structure perturbation creating new electron pathways. A convenient solution is specific modifier adsorption onto the semiconductors'' surface, providing a sufficient level of electronic coupling. Photoelectrodes made of nanocrystalline TiO₂ modified by cyanoferrate,^13,23 and ruthenium²⁴ complexes, thiamine, folic acid,²⁵ and carminic acid²⁶ demonstrated PEPS behavior.Surprisingly, we observed the PEPS effect on non-modified Ti/TiO₂ obtained by anodation of Ti plates.Highly ordered arrays of anatase Ti/TiO₂ were obtained. Crystallinity was proved by XRD (Fig. S1a^†). Fig. 1a shows a SEM image of TiO₂ nanotube arrays obtained as described above. According to SEM image, an average pore diameter is ca. 60 nm. As reported, highly ordered TiO₂ nanotubes possess a short charge transport distance and little carrier transport loss. Therefore, highly ordered TiO₂ nanotube arrays fabricated by electrochemical anodization of titanium may exhibit some enhanced capacity of electron transfer than non-oriented ones of random mixture.¹⁰Open in a separate windowFig. 1(a) SEM image of the TiO₂ nanotubes array. The inset shows cross-section view. (b) Scheme of a cell for photocurrent measurements experiment, CE – counter electrode, RE – reference electrode, WE – working electrode.According to Mott–Schottky analysis, at potential bias more positive than −0,697 V vs. Ag/AgCl reference electrode upwards band bending occurs (Fig. S2^†). Heat treatment in a nonoxidizing atmosphere leads to Ti³⁺ formation. Appearance of Ti³⁺ self-doping was proved by EDX analysis (Fig. S1b^†). It was previously reported that Ti³⁺ introduces gap states which act as recombination centers and pathways for electron transfer.^27–29 Ti³⁺ species in reduced TiO₂ introduce a gap state between valence and conduction bands.^27,28We studied dependence of photocurrent on applied potential. Ultraviolet irradiation (365 nm) gave positive photocurrent for all potentials studied in range from −0.6 V to 0.6 V vs. Ag/AgCl reference electrode (Fig. S3^†). The photocurrent increases as the potential becomes more positive, but eventually saturates. The dependence of the current on the potential under blue irradiation (405 nm) had a different character. Sigmoid function with inflection point at 0–0.2 V was observed for blue light.It should be noticed that photocurrent plotted against time on Fig. 2–4 as well as against potential on Fig. S3^† is ΔI = I_{under illumination} − I_{in darkness}. Steady state current values were used for calculations.Open in a separate windowFig. 2Photocurrent curves under chopped irradiation by (a) 365 nm UV LED, (c) 405 nm blue LED at applied potential bias +300 mV vs. Ag/AgCl, and corresponding scheme of electron pathway at +300 mV polarization under irradiation by (b) 365 nm UV LED and (d) 405 nm blue LED.Open in a separate windowFig. 3Photocurrent curves under chopped irradiation by (a) 365 nm UV LED, (c) 405 nm blue LED at applied potential bias −300 mV vs. Ag/AgCl, and corresponding scheme of electron pathway at −300 mV polarization under irradiation by (b) 365 nm UV LED and (d) 405 nm blue LED.Open in a separate windowFig. 4(a) XOR logic realized on negatively polarized (−0.3 V) pristine Ti/TiO₂ by two source irradiation, input A – UV light (365 nm), input B – blue light (405 nm); blue light gives anodic photocurrent, UV – cathodic photocurrent. The current, significantly different from the dark one, is taken as output 1, otherwise – 0. When irradiated by blue and UV light simultaneously, anodic and cathodic current compensate each other, and no total photocurrent observed. Thus output 0, when both inputs are 1 (b) OR logic realized on positively polarized (+0.3 V) non-modified Ti/TiO₂ by two sources of irradiation. Irradiation by any of them, blue or UV, gives anodic photocurrent.At +300 mV vs. Ag/AgCl irradiation by both blue and ultraviolet light give anodic photocurrent (Fig. 2a and c). The UV-irradiation (λ = 365 nm, 5 mW cm⁻²) excites electron directly to the conduction band (CB) of TiO_2, which is further transferred to conducting titanium support (Fig. 2b). When Ti/TiO₂ electrode in thermodynamic equilibrium with electrolyte, an upward surface band bending occurs at the semiconductor–liquid junction. This phenomenon obstructs electron injection from the conduction band into the electrolyte and forces electron drift to conducting substrate. The fast and steady photocurrent production/extinction upon light on/off indicates efficient charge separation and low recombination.Blue light (λ = 405 nm, 70 mW cm⁻²) is characterized by lower energy than UV-irradiation, which is not sufficient to excite the electron to CB. But electron excited by blue light can be trapped by Ti³⁺ located close to the conduction band and transferred to conduction support from these levels (Fig. 2c). An initial current spike following by an exponential decrease suggesting a fast recombination process. It should be also noticed than when irradiation is switched off photocurrent ‘overshoots’ as the remaining surface holes continue to recombine with electrons.At more negative potential (−300 mV vs. Ag/AgCl, for example) applied to non-modified anodized Ti/TiO₂ photoelectrode, we observed anodic photocurrent during irradiation by UV light (Fig. 3a) whereas blue irradiation gave anodic photocurrent (Fig. 3c). Excitation within bandgap by UV-irradiation leads to cathodic photocurrent (Fig. 3b). In the case of irradiation by blue light, electron trapping by Ti³⁺ occurs in the same manner as at +300 mV polarization. But at negative polarization, the energy landscape is such that electron transport to electron donor in solution is preferable (Fig. 3d). As a result, cathodic current occurs.Thereby, photoelectrode activity of non-modified anodized Ti/TiO₂ can be switched from anodic to cathodic and vice versa by applying various potentials and various photon energies. This is the effect of photoelectrochemical photocurrent switching.Thereby, when Ti/TiO₂ is irradiated simultaneously by blue and UV light being negatively polarized, competition between cathodic and anodic photocurrents occurs. Returning to Boolean logic, the PEPS effect allows us to perform annihilation of two input signals and implement optoelectronic XOR logic gate. XOR logic operation outputs true (1) only when input values are different and yield zero otherwise.It is necessary to assign logic values to input and output signals to analyse the system based on Ti/TiO₂ PEPS effect in terms of Boolean logic. Logical 0 and 1 are assigned to off and on states of the LEDs, respectively. Different wavelengths (365 and 405 nm) correspond to two different inputs of the logic gate. In the same way, we can assign logic 0 to the state when photocurrent is not generated and logic 1 to any nonzero photocurrent intensity irrespectively on its polarization (cathodic or anodic). Fig. 4 demonstrates how different types of Boolean logic are realized by irradiation of Ti/TiO₂. Light sources are denoted here as inputs, UV light – A and blue light – B. If the corresponding light source is switched ON and illuminates photoelectrode Ti/TiO₂, this input is ‘1’, otherwise, it''s ‘0’. The photocurrent is read as output. It''s considered to be ‘1’ if significantly differs from dark value and ‘0’ otherwise.At −300 mV vs. Ag/AgCl, pulsed irradiation with UV diode (365 nm, 5 mW cm⁻²) results in anodic photocurrent, which is consistent with electron excitation to CB and transfer to conducting support. Irradiation with blue LED (405 nm) gives cathodic photocurrent due to electron capture by Ti³⁺ states following by transferring to electron acceptor in solution. Simultaneous irradiation with two LEDs with adjusted intensity yields zero net current as anodic and cathodic photocurrents compensate effectively (Fig. 4a).At positive potentials, pulsed irradiation with UV diode gives anodic photocurrent pulses, as well as the blue one. It is interesting to note that when two sources of light are simultaneously irradiated, the photocurrents created by each of them individually do not summarize. At +300 mV, photocurrent output under the influence of two light inputs (365 nm and 405 nm) follows OR logic giving positive output if at least one of inputs is positive (Fig. 4b). Fig. 5 demonstrates the reconfigurable logic system which characteristics can be changed via an appropriate polarization of the photoelectrode regarded as programming input. Two irradiation sources are considered as inputs. OR/XOR logic is realized depending on programming input.Open in a separate windowFig. 5A reconfigurable logic system based on non-modified Ti/TiO₂. Light sources are inputs. The choice between XOR and OR function is determined by programming input of potential bias. At +300 mV OR logic is realized, at −300 – XOR logic. Corresponding truth table is presented.In summary, PEPS effect on modified nanocrystalline TiO₂ was previously discussed a lot.^13,23–26 In this work we report the same phenomenon for pristine anodized Ti/TiO₂ system. Due to substructure of Ti/TiO₂ system, it shows characteristic response to various range of illumination, including visible range and polarization. The Ti/TiO₂ system is a simple and robust model of chemical logic gates. Suggested mimicking of logic functions in aqueous solutions allows further integration of element into communication with living objects¹⁶vs. intrinsically associated photooxidation and degradation, but rather activation for needed function.³⁰     

Hyperpolarization study on remdesivir with its biological reaction monitoring via signal amplification by reversible exchange

Our experiments indicate hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by para-hydrogen. SABRE-based biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out. It represents the first successful para-hydrogen based hyperpolarization application in biological reaction monitoring.

Hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by para-hydrogen. Biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out.

Nuclear magnetic resonance is a versatile and powerful analytical method for real-time monitoring of significant bio-catalyzed reactions. However, even though NMR has great potential as a reaction monitoring system, providing much structural information, it has not been studied in depth due to low sensitivity. To enhance the sensitivity, the hyperpolarization technique has been suggested which has long been acknowledged as a breakthrough in reaction monitoring by NMR.There are major hyperpolarization techniques, generating non-Boltzmann population distribution for hyperpolarized signal to noise such as dynamic nuclear polarization,^1–5 spin-exchange optical pumping,^6–8para-hydrogen induced polarization (PHIP),^9–11 and signal amplification by reversible exchange (SABRE).^12–14 In the case of para-hydrogen-based SABRE, the substrate and the para-hydrogen bind to a catalyzing metal complex together, thus allowing polarization to be transferred to the substrate through scalar coupling. To achieve better enhancement, the iridium N-heterocyclic carbene complex¹⁵ exhibits the highest polarization transfer efficiency, which delivering an 8100-fold enhancement in ¹H NMR signal amplification relative to non-hyperpolarized pyridine. Additionally, enhancements can be increased by employing the bulky electron-donating phosphines of the Crabtree catalyst.¹⁶ Most iridium N-heterocyclic carbene catalysts are produced as [Ir(H)₂(NHC)(substrate)₃]Cl while they are capable of delivering various NMR signal gains such as ¹H,^17–1913C,^9,20,2115N,^22–2419F,^25,2631P.²⁷ Recently, a published work has described the extension of the SABRE substrate scope to include a wide range of common drugs such as tuberculosis drugs,²⁸ antifungal,²⁹ and antibiotic agents.^30,31 It is mainly N-heterocyclic compounds with low molecular weight. Hyperpolarization experiments using large molecular weight COVID-19 drug candidates have rarely been reported.³² Here, we extend the current scope of biologically relevant SABRE substrates to remdesivir and monitor its enzymatic hydrolysis.SABRE has been widely considered as a potentially promising reaction monitoring tool for the real-time reaction via hyperpolarization.^33,34 After its successful application on the amide-coupling reaction monitoring, it could not be applied to the biological reaction monitoring due to the solvent used for the reaction, mild biological reaction conditions, and mostly, small molecule polarization capacity. Therefore, its direct application on the biological reaction could open up new possibilities in the real-time reaction monitoring via hyperpolarization.To overcome this COVID-19 pandemic, many researchers have engaged in drug development including drug repurposing. Recently, remdesivir has received emergency use authorization from the FDA, as the first organic medicine to treat COVID-19 around the world. Its prodrug form has been controversial as its intact form is not detectable even after two hours post-injection and as its efficiency for all clinical treatment should also be catalyzed by several key biological reactions including esterase hydrolysis reaction.^35–37 Therefore, further research on its molecular level of understanding is still required for enhanced drug development. Along with that, repurposing nucleoside analogue drugs have been considered as the attractive future drug candidates to overcome this pandemic and beyond. They target the RNA polymerase and prevent viral RNA synthesis in a broad spectrum of RNA viruses, including human coronaviruses.^38,39 Thus, to develop the most appropriate repurposing nucleoside analogue drug candidates for COVID-19, in-depth timely research on its pharmacokinetics and pharmacodynamics at the molecular level is also essential to overcome this pandemic and its consequent recurrences.In our previous study, we reported the hyperpolarization on the several anti-viral drug candidates of COVID-19.³² However, these drug candidates have been reported rather ineffective in treating COVID-19.⁴⁰ Furthermore, even though those unprecedented hyperpolarization on the large drug molecules are new, their polarizations are only done in methanol solvent, which is not applicable in a biological form.³² Our research results indicate successful hyperpolarization of remdesivir via SABRE under mild conditions and hyperpolarization performed in DMSO, a more non-toxic solvent for in vitro application. To provide a more clinical perspective of using this technique, its biological reaction by enzyme was successfully monitored by signal enhancement via SABRE. Moreover, to widen its future applications, we added one more Ir-catalyst by matching external magnetic field condition for efficient polarization transfer to remdesivir. Our findings will expand newly applicable research areas, not only in biological reaction monitoring via NMR, but also in other biomedicine research, in order to cope with dreadful diseases in the future.Remdesivir structure has several potential key polarization sources for SABRE: nitrile, amine, and triazine. However, its complex structure and large molecular weight have been considered as the limiting factors for hyperpolarization. Fig. 1 depicts the normal signal and its hyperpolarized signal after SABRE using IMes-Ir-catalyst, which shows the different extent of hyperpolarization of remdesivir. Among the amplified proton signals, proton 6 represents the highest hyperpolarization attached to the 5′-carbon of the nucleoside. However, its polarization indicates no major difference compared to those protons in the whole structure.Open in a separate windowFig. 1Remdesivir molecular structure and its normal ¹H NMR signal in the methanol-d₄ solvent (black spectrum). Hyperpolarized signals from remdesivir after SABRE in the presence of 130 G external magnetic field in the methanol-d₄ solvent (red spectrum).Therefore, we can anticipate its polarization transfer is mostly from the SABRE-Relay^41–43 or SPINOE,^44–46 which are discussed more on conclusion. To optimize hyperpolarization, the external magnetic field is changed, and its polarization is maximized at around 130 G.However, no major difference was noted in the extent of hyperpolarization in different magnetic fields, which could have been due to Ir-catalyst''s fast exchange. Furthermore, its polarization transfer could be from other factors such as SPINOE, other than from the Zeeman effect and J-coupling matching condition. Referring to a recent study on the SABRE hyperpolarization difference between Ir-catalysts,⁴⁷ we tested the SABRE with Crabtree''s-Ir-catalyst, which indicates the different polarization number. Interestingly, its polarization confirmed that the number of hyperpolarization using the Crabtree''s-Ir-catalyst was slightly higher than IMes-Ir-catalyst. The hyperpolarization patterns in the different magnetic field also present no major changes from the different Ir-catalyst (Fig. 2 and S1^† for structures of Ir-catalysts). Remdesivir is considered to be one of the most important treatments amid this pandemic due to its usage in blocking viral RNA production, leading to an additional study on hyperpolarization in which a more biological solvent has been conducted. Interestingly, SABRE in the CD₃SOCD₃ with IMes-Ir-catalyst shows the highest polarization efficiency with approximately 17-fold enhanced signal (Fig. 3). DMSO has various biological impacts, such as the ability to increase the skin penetration of chemicals. It can pass through biological membranes, including human skin, probably by changing lipid packing structure and producing breaks in the bilayer.^48,49 This result observed in the current research opens a new possibility for applying the in vitro experiment with biological tests since DMSO has been widely used in the in vitro drug test.^50,51 Its polarization result of remdesivir among the Ir-catalyst led to higher IMes-Ir-catalyst than Crabtree''s-Ir-catalyst, different from the CD₃OD. This indicates the polarization transfer mechanism with chelating structure is not solely dependent on the solvent or catalyst. Furthermore, the polarization trend in its structure is the highest in the proton of 9, followed by the proton of 5, which bonded with 5′-carbon of the nucleoside. This different trend in each Ir-catalyst indicates that the polarization transfer efficiency varies depending on solvents in different external magnetic fields and different solvent systems.Open in a separate windowFig. 2Signal amplification value (SE) of individual protons from hyperpolarized remdesivir using IMes-Ir-catalyst and Crabree''s-Ir-catalyst.Open in a separate windowFig. 3(a) ¹H spectrum of remdesivir before (black spectrum) and after SABRE (red spectrum) in the DMSO-d₆; (b) signal amplification value (SE) of individual protons from hyperpolarized remdesivir using IMes-Ir-catalyst and Crabtree''s-Ir-catalyst.Remdesivir activates analogue, inhibits RNA-dependent RNA polymerase, and prevents viral RNA synthesis as a phosphoramidate prodrug.⁵² The activation pathway of remdesivir has been proposed to have four steps: (1) cell entrance; (2) enzymatic elimination of masking group with 2-ethylbutyl ester and phenoxy; (3) phosphorylation; and (4) incorporation into COVID-19 RNA.⁵³ The masking group of remdesivir performs increasing hydrophobicity to facilitate cellular entry.⁵⁴ Also its inventor found that the proton of 7 was shifted to 3 to 4 ppm when the masking group of remdesivir was removed.^55,56 Monitoring hydrolysis of a 2-ethylbutyl ester by esterase confirmed the proton of 7* in 3.2 ppm via hyperpolarization (Fig. 4a). The splitting pattern of 7* is controversial because of its doublet instead of quartet. It attributes to several factors. Because of the 5-membered ring intermediate from remdesivir, the splitting pattern of 7* could be affected. The initial metabolism of remdesivir produces an intermediate of cyclopentane containing 7* is made.⁵⁷ Therefore, stereochemical relations in the equilibrium among protons in 5-membered rings cannot be determined by simply measuring coupling constants, except in cases where the substitution pattern of the specific ring system has been carefully investigated. It could be covered by a water peak close to 7*. Another possibility is that hyperpolarized proton 8 of the 2-ethyl butyl group that is released by enzymatic hydrolysis can be observed. However, the cleavage of the phenoxy group is hard to prove via spectra due to little variation in the signal of aromatic region (Fig. S2^†). Its normal cleaved remdesivir signal after the same reaction time and condition was not shown in a scan and its maximum polarization was calculated by ∼22 enhancement after comparing with the multiple scan average (Fig. 4b and S3^†). To the best of our knowledge, this is the first study that conducts hyperpolarization reaction monitoring via SABRE in biological condition is conducted for the first time. Furthermore, its NMR-based reaction monitoring on a biologically important prodrug suggests that significantly wide applications in biomedical research. Its application can be significantly widened in the biomedical researches.Open in a separate windowFig. 4(a) ¹H spectra of enzymatic hydrolysis monitoring of remdesivir; elimination of 2-ethylbutyl ester group; (b) ¹H spectra of remdesivir; enzymatic hydrolysis after 120 min (black spectrum) and amplified through hyperpolarization (red spectrum) at the same time.     

Photocatalytic degradation of organic pollutants through conjugated poly(azomethine) networks based on terthiophene–naphthalimide assemblies

A conjugated poly(azomethine) network based on ambipolar terthiophene–naphthalimide assemblies has been synthesized and its electrochemical and UV-vis absorption properties have been investigated. The network has been found to be a promising candidate for the photocatalytic degradation of organic pollutants in aqueous media.

A conjugated two-dimensional poly(azomethine) network based on ambipolar terthiophene–naphthalimide assemblies has been synthesized and its electrochemical and UV-vis absorption properties have been investigated.

Due to the rapid growth of urbanization and intensive industrialization, pollution has evolved into a serious concern that produces a great negative impact on human health and the environment.^1,2 Therefore, many efforts are currently devoted to addressing environmental remediation through the degradation and removal of hazardous contaminants.^3–5 In this regard, photocatalysis has been identified as a suitable approach for environmental remediation given that it is an energy efficient technique that does not require chemical input and does not produce sludge residue.⁶ In recent years, organic semiconducting polymers have evolved into a new type of metal-free and heterogeneous photocatalyst suitable for solar-energy utilization.⁷ The modularity of organic polymers allows the efficient tunning of their electronic and optical properties by bottom-up organic synthesis through the choice of suitable monomeric building blocks.^8–10 Within this context, there is a growing demand for new organic polymeric semiconductors carefully designed to have suitable energy levels of the frontier orbitals, an appropriate bandgap and good intrinsic charge mobility.¹¹For the design of suitable polymeric semiconductors for photocatalysis, it is not only important that the photocatalysts absorb light in the visible light range but also an efficient dissociation of the photogenerated charge carriers is required. The combination of electron-poor acceptor (A) and electron-rich donor (D) moieties in the polymer structure may prevent a fast recombination process following photoexcitation.¹² In addition, it has been found that polymers networks bearing conjugated moieties may exhibit π-stacked columns that can facilitate charge transport.¹³In this respect, molecular and polymeric materials based on the combination of oligothiophene^14,15 and naphthalimide moieties^16,17 connected through conjugated linkers have shown to be very effective in order to efficiently tune their frontier orbital levels and produce tunable organic semiconductors with good charge transport properties.^18–24 As an example, in Fig. 1 is depicted the structure of NIP-3T, an ambipolar organic semiconductor, for which the one-electron HOMO–LUMO excitation consists of the displacement of the electron density from the HOMO, primarily localized on the oligothiophene fragment, to the LUMO, localized on the naphthalimide unit.²⁵Open in a separate windowFig. 1(a) Monomer containing an electron donor terthiophene system directly conjugated with an electron acceptor naphthalimide moiety through a conjugated pyrazine linker (NIP-3T). (b) HOMO and (c) LUMO computed orbital topologies for NIP-3T.²⁵Among conjugated polymers, poly(azomethine)s have found application as organic semiconductors in heterogeneous photocatalysis because of their π-conjugated system and suitable band levels matching the redox window of water.²⁶ The incorporation of D–A monomeric assemblies into poly(azomethine) networks represents an efficient strategy to obtain ambipolar polymeric networks with tunable frontier orbital levels for photocatalytic applications. Thus, in this communication we report the synthesis of a novel donor–acceptor poly(azomethine) network (NIP3T-ANW, Scheme 1) based on NIP-3T monomers. The potential of this system as photodegrading agent for the elimination of contaminant organic dyes in aqueous media is also explored.Open in a separate windowScheme 1Schematic representation of the synthesis of NIP3T-ANW.The synthesis of the macromolecular poly(azomethine) network NIP3T-ANW is acomplished through Schiff-base reactions between trigonal monomers endowed with amine functionalities (TAPB,²⁷Scheme 1) and linear naphthalimide–thiophene-based monomers endowed with complementary aldehyde functional groups (NIP3T2CHO,²⁴Scheme 1). Typically, both monomers were dissolved in an o-dichlorobenzene/n-butanol/acetic acid (1 : 1 : 0.1) mixture, which was then heated at 120 °C under solvothermal reaction conditions for 72 h. A black solid was obtained which was insoluble in common solvents such as water, acetone, THF, toluene or chlorinated solvents like dichloromethane or chloroform. The obtained solid was washed several times with THF to remove the starting materials and low-molecular weight by-products. After drying under vacuum, a black solid was obtained. The yield, as determined by weight, was 98%.To investigate the chemical nature of the material, as well as to determine the conversion of the functional groups after the reaction, we have employed attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy (Fig. 2). The bands arising from the NH₂ stretching (3000–3400 cm⁻¹) and NH₂ deformation (1650 cm⁻¹) vibrations of the primary amine group of TAPB and the signals from the aldehyde groups of NIP3T2CHO around 2870 (C–H stretching) and 1663 cm⁻¹ (C O stretching) are virtually absent in the NIP3T-ANW spectrum. In addition, a prominent new band is found at 1573 cm⁻¹, which can be assigned to the C N stretching vibration of the imine linkages within the newly formed poly(azomethine) network.^28–30Open in a separate windowFig. 2(a) IR spectra of NIP3T2CHO (blue), TAPB (red) and NIP3T-ANW (black). (b) Solid-state ¹³C CP-MAS NMR spectrum of NIP3T-ANW.Solid-state ¹³C cross-polarization magic angle spinning NMR (¹³C CP-MAS NMR) spectrum (Fig. 2) reveals the characteristic imide signals of the 1,8-naphthalimide moiety at 164.4 ppm, as well as the signal corresponding to the imine carbon at 154 ppm and a signal at 148 ppm which can be assigned to the aromatic carbon neighbouring the nitrogen of the C N group. The absence of the sp² carbons from the NIP3T2CHO ²⁴ aldehyde functionalities above 180 ppm satisfactorily confirms the condensation between the aldehyde and the amine derivatives.Due to the rigidity and geometry of the building blocks, the imine linkers could be ideally generated in such a way that result in a canonical layered hexagonal structure³¹ as predicted by theoretical calculations (Fig. S1 and S2^†). However, in the actual framework, X-ray diffraction (XRD) measurements indicate that the material is mainly amorphous with only some ordered regions, as indicated by the good agreement between the weak and broad diffraction peaks observed at 2θ values larger than 3 and those predicted by calculations for the ideal canonical layered hexagonal structure (Fig. S3^†). In this regard, NIP3T-ANW was submitted to an exfoliation process following a previously described protocol³² for the exfoliation of two-dimensional polymers (see ESI^† for details). The exfoliated material was analysed by dynamic light scattering (DLS) showing a monomodal size distribution of ca. 400 nm (Fig. S4^†) and transmission electron microscopy (TEM) reveals a sheet-like structural aspect (Fig. S5^†).Thermogravimetric analysis of the poly(azomethine) network NIP3T-ANW shows that the degradation starts at around 450 °C and only 40% weight loss is observed at 700 °C (Fig. S6^†). This thermal stability is significantly higher than that observed for NIP3T (Fig. 1), the analogous molecular system based on terthiophene connected with naphthalimide through pyrazine for which the degradation starts at 200 °C (Fig. S6^†).^22,25In photocatalysis mediated by semiconductors, electron–hole pairs (excitons) are generated after light absorption and afterwards dissociate into free charge carriers that can be utilized for redox reactions^33,34 such as CO₂ fixation,³⁵ water splitting³⁶ or organic mineralization.³⁷ Some of the crucial factors that make the photocatalytic process favourable are the levels of conduction and valence as well as the width of the band gap.^38–40 Thus, in order to characterize these parameters, the electrochemical and optical properties of NIP3T-ANW have been analysed.The electrochemical properties of NIP3T and NIP3T-ANW were studied by cyclic voltammetry (Fig. 3). Both materials show ambipolar redox behaviour in which the reversible reduction processes are characteristic of the naphthalimide unit, while the oxidation processes can be ascribed to the conjugated oligothiophene moiety.^19–22,24 For NIP3T-ANW, the first reversible reduction wave (−1.29 V) is shifted to less negative values in comparison with NIP-3T (−1.41 V). On the other hand, the first oxidation half wave potential for NIP3T is observed at +0.41 V and for NIP3T-ANW at +0.44 V. These shifts agree with the electron acceptor ability of the imine linker.Open in a separate windowFig. 3(a) The UV-vis DRS spectra of NIP3T and NIP3T-ANW. (b) Cyclic voltammetry of the NIP3T monomer and the corresponding polymer.The absorption spectrum of NIP3T-ANW as determined by UV-vis diffuse reflectance spectroscopy (UV-vis DRS, Fig. 3) shows a strong absorption in all the UV-vis range, extending even to the near infrared. This broad absorption is red-shifted in comparison with the one observed for NIP3T (Fig. 3), which reflects the formation of the new polymer network with an extended conjugation through the alpha positions of the terthiophenes.Using the corresponding cut-off wavelengths, the optical band gaps E_g found for NIP3T and NIP3T-ANW are 1.59 and 1.42 eV respectively. This optical result suggests that the incorporation of the NIP3T core into an extended conjugated system efficiently harvests photons from the visible range, even extending into the near IR region.To shed some light into the degree of crystallinity of the synthesized NIP3T-ANW network, we have carried out a battery of density functional theory (DFT)-based calculations with the QUANTUM ESPRESSO plane-wave DFT simulation code⁴¹ (see details in ESI^†). We have considered periodic boundary conditions to obtain a fully-relaxed ground-state crystal structure. Optimization of the cell-shape and size, simultaneously to the relaxation of the structure, reveals a hexagonal 2D lattice with an optimized parameter of 48.46 Å. Different interlayer stacking fashions have been tested, with only one yielding a good agreement with the experimental diffractogram from 2θ values >3°. The most favourable stacking predicted by theory consists in an intermediate configuration between the perfectly eclipsed and staggered configurations, with an interlayer distance of 3.42 Å, and permits an adequate accommodation of the layers profiting adjacent pores. Details on the structure can be found in the ESI.^†Additionally, we have computed the electronic band diagram of the obtained crystal structure along the high-symmetry k-path Γ → K → M → Γ, revealing a wide-gap (1.91 eV) semiconducting character, with rather dispersive valence and conduction bands, mainly resembling the molecular HOMO and LUMO of the molecular building blocks (see Fig. S7^†). Besides, computed time-dependent DFT (TDDFT) UV-vis spectrum manifests an excellent agreement with the experimental UV-vis spectra (Fig. S8^†). A broad and pronounced peak-feature is obtained between 600 and 800 nm, centred at around 720 nm (1.7 eV), which agrees with the optical gap of 1.6 eV found for NIP3T from Fig. 3a. This feature corresponds to electronic transitions between the valence and conduction bands, with an energy difference of around 0.2 eV between the optical and the electronic gap, which indicates that charge relaxation in excited states is not much significative. The good agreement between theoretical predictions on the canonically periodic computed system and the experimental evidences seems to justify the presence of some high-crystallinity regions from the synthesis.The band gap of a semiconductor material and the reduction and oxidation potentials are key parameters which determine its light-harvesting properties and types of reaction that can be conducted and therefore the overall photo-catalytic activity. A shift in the adsorption edge of a semiconductor towards longer wavelengths implies a narrower band gap and the efficient harvesting of a wider photons range.⁴²NIP3T-ANW seems to be an appealing material to be utilized as photocatalyst given (i) the optimal light harvesting properties as shown by the optical characterization, (ii) the efficient generation of electron–hole pairs owing to the insertion of terthiophene moieties, and (iii) the right energy band positions for the material.⁷ We therefore evaluated the photocatalytic activity of NIP3T-ANW under white light for the degradation of a model organic pollutant (Rhodamine B dye, RhB) in aqueous solution.⁴³ In the absence of catalyst, RhB remains stable in solution under illumination (Fig. 4a and S9^†). However, in presence of NIP3T-ANW nearly 90% of RhB in an aqueous solution is degraded after 120 min, showing the enhanced catalytic activity of the material (Fig. 4a and S10^†). Furthermore, a good stability is shown upon 4 straight catalytic cycles (Fig. 4b, S11 and S12^†). In contrast, in the presence of the NIP3T moiety, only a 55% degradation of RhB is observed in the same timeframe (Fig. 4a and S11^†).Open in a separate windowFig. 4RhB degradation curves. (a) Comparison between the degradation effect of NIP3T, NIP3T-ANW and without catalyst. (b) NIP3T-ANW stability after four recycling cycles.In the photocatalytic degradation of organic pollutants, they are typically broken down through the attack of superoxide and hydroxyl species, formed when atmospheric oxygen reacts with photogenerated electrons or when water or OH ions are oxidized by holes, respectively.⁴⁴ Additionally, electron–hole pairs (or excitons) can directly reduce or oxidize organic pollutants in aqueous environments. Consequently, the evaluation of the photodegradation mechanism of organic pollutants, despite challenging, can provide meaningful insights about the nature of a semiconductor photocatalyst.⁴⁵ With the aim of evaluating the photodegradation mechanism we performed the measurements in the presence of different scavengers, namely an aqueous solution of AgNO₃ (100 mg L⁻¹), which captures photogenerated electrons, or triethanolamine (TEOA), which traps photogenerated holes (Fig. S13^†).^46,47 In the presence of Ag⁺ we could observe that the photocatalytic efficiency is enhanced, while the addition of TEOA quenched the performance, therefore suggesting that holes are the active specie in the photodegradation mechanism (Fig. S14^†).In summary, we have presented an approach towards the incorporation of D–A π-conjugated monomeric assemblies into poly(azomethine) networks to yield a purely organic semiconductor for the photocatalytic degradation of organic pollutants in aqueous media. The poly(azomethine) network benefits from a straightforward poly(condensation) approach which favourably competes with the elaborate high-temperature protocols applied for the preparation of inorganic materials. This work enriches the family of donor–acceptor organic semiconductor networks and, given its modular nature, paves the way for the development of a promising family of materials for photocatalytic applications.     

The synthesis of highly active carbon dot-coated gold nanoparticles via the room-temperature in situ carbonization of organic ligands for 4-nitrophenol reduction

Due to the serious pollution issue caused by 4-nitrophenol (4-NP), it is of great importance to design effective catalysts for its reduction. Here, a novel and simple strategy was developed for the synthesis of carbon dot-decorated gold nanoparticles (AuNPs/CDs) via the in situ carbonization of organic ligands on AuNPs at room temperature. The enhanced adsorption of 4-NP on CDs via π–π stacking interactions provided a high concentration of 4-NP near AuNPs, leading to a more effective reduction of 4-NP.

Due to the serious pollution issue caused by 4-nitrophenol (4-NP), it is of great importance to design effective catalysts for its reduction.

With the rapid development of the global economy and the continuous progress of the society, environmental problems, especially water pollution caused by nitroaromatic compounds, have become increasingly serious during the last decade.^1,2 As one of the toxic phenolic pollutants, 4-nitrophenol (4-NP) is usually found in the wastewater discharged from many chemical industries, which causes severe environmental issues and also a serious toxic effect on the living organisms.^3–6 Hence, 4-NP has been classified as a priority toxic pollutant by the US Environmental Protection Agency.⁷ In contrast, 4-aminophenol (4-AP), a product of 4-NP, is less toxic and an important intermediate that can be applied in many fields.⁸ Therefore, developing a novel method to effectively convert hazardous 4-NP to nontoxic 4-AP is urgent for solving the environmental issues.⁹It has been reported that 4-NP can be reduced to 4-AP by borohydride ions (BH₄⁻) enabled by catalysts, which plays an important role in this process. Among various catalysts, noble-metal materials (especially Au) have been demonstrated to be effective catalysts and are still the main catalysts used for 4-NP reduction.^10–13 In any heterogeneous catalysis process, the catalytic reaction must occur on the surface of the catalyst.^14–16 Therefore, the adsorption of reagents on the catalyst surface is a vital process before the chemical reaction. Recently, the efficient adsorption of reagents with aromatic rings on π-rich supports has been proved based on π–π interactions.^17–19 As an aromatic compound, 4-NP is also a π-rich molecule in nature, and its adsorption on a carbon-based catalyst by these π–π stacking interactions has also been demonstrated.^20,21 By decorating metal nanoparticles (MNPs) on these supports, the catalytic activity of MNPs toward the reduction of 4-NP to 4-AP by NaBH₄ has also been effectively enhanced via a synergistic effect.^22,23 Based on this, various π-rich carbon materials like carbon fibers,²⁴ carbon nanotubes,²⁵ graphene oxide,²⁶ reduced graphene oxide,²⁷ and graphitic carbon nitride²⁸ have been utilized as supports to prepare metal/carbon-based catalysts with enhanced catalytic activity. However, these methods suffer from drawbacks such as a multiple-step preparation process, prior functionalization, high cost and low yields, limiting their wide practical applications.^29,30 More importantly, as described previously, the reduction of 4-NP mainly occurs on the AuNP surface;³¹ thus, we can speculate that anchoring smaller π-rich carbon materials on the AuNP surface may lead to higher catalytic activity for the 4-NP reduction. Carbon dots (CDs) with the structure of sp² carbons^32,33 can adsorb 4-NP via π–π stacking, with the additional advantages of excellent stability and smaller size.³⁴ Thus, the catalytic activity of AuNPs for 4-NP reduction can be improved by the surface decoration of CDs, which, however, has not been reported before.Herein, a convenient and simple method was proposed to synthesize CD-decorated AuNPs (AuNPs/CDs) via the room-temperature in situ carbonization of cetylpyridinium chloride monohydrate (CPC) pre-adsorbed on AuNPs as an organic ligand. This AuNP/CD hybrid was demonstrated to have higher catalytic activity for the reduction of 4-NP, which was about 2.7-fold higher than that of AuNPs. The improved catalytic activity of AuNPs/CDs can be attributed to the synergistic effect between AuNPs and CDs.According to previous research, CPC can be carbonized to carbon dots in the presence of NaOH.^35,36 Inspired by this, we used CPC as both the capping and reducing agent to synthesize AuNPs in the presence of NaOH, and the synthesis process is displayed in Fig. 1A. After adding HAuCl₄ into an aqueous solution of CPC, yellow suspended solids were generated quickly (Fig. 1A(a) and (b)), which should be attributed to the formation of CPC-Au(i) between AuCl₄⁻ and CPC. Fig. 1B shows the UV-vis spectra of the aqueous solution of CPC before and after the addition of AuCl₄⁻. The obvious absorption peak at 340 nm (green) should be due to the generated CPC-Au(i). The generated Au(i), confirmed by the XPS analysis results (Fig. 1D), can originate from the reduction of Au(iii) by CPC because there are no extra reducing agents present in this system. After adding NaOH into the above-mentioned CPC-Au(i) solution at room temperature (Fig. 1A(b) and (c)), the color of the solution gradually changed to dark red (Fig. 1A(c)). The UV-vis spectrum of the above-mentioned mixture solution was then recorded. The absorbance between 280 and 450 nm proved the formation of CDs due to the carbonization of CPC under alkaline conditions;³⁵ moreover, the obvious absorption peak at 520 nm (Fig. 1C (red)), corresponding to the surface plasmon resonance (SPR) of AuNPs,³⁷ indicated the formation of AuNPs in this process. The formation of AuNPs could be attributed to the further reduction of CPC-Au(i) after the addition of NaOH. XPS analysis was also performed to investigate the oxidation state of the Au species in the process of AuNP synthesis. The high-resolution Au 4f XPS spectra shown in Fig. 1D and E indicate the presence of different Au species in these two samples. For CPC-Au(i) (Fig. 1D), the four evident peaks at 84.8, 88.4 eV and 87.4, 91.1 eV were assigned to the Au 4f_7/2 and Au 4f_5/2 signals,³⁸ respectively, indicating the co-existence of nonmetallic Au⁺ and Au³⁺ in this sample.³⁹ However, for AuNPs/CDs (Fig. 1E), two typical binding energies at 86.8 eV and 83.1 eV, attributed to the binding energies of metallic Au(0),⁴⁰ were clearly observed, indicating the successful reduction of Au(iii) and/or Au(i) to Au(0) in the presence of NaOH.Open in a separate windowFig. 1(A) Diagram for the synthesis of AuNP/CD nanocomposites at room temperature. (B and C) The UV-vis absorption spectra of CPC (black), CPC-Au(i) (green), CDs (blue) and AuNPs/CDs (red) in aqueous solutions, respectively. The high-resolution XPS spectra of Au 4f in CPC-Au(i) (D) and AuNPs/CDs (E). Fig. 2A displays the TEM image of the synthesized AuNPs/CDs. From the image, it can be seen that the monodispersed AuNPs/CDs are spherical, with an average size of 3.5 ± 0.8 nm and a standard deviation of the particle sizes of 22.9% (Fig. S1^†). This relatively small size should be attributed to the use of CPC as a capping agent, which can effectively control the growth of AuNPs. Fig. 2B shows the HRTEM image of AuNPs/CDs; the characteristic lattice spacing of 2.06 Å can be attributed to the (200) plane of face-centered cubic (fcc) gold,⁴¹ which also indicates the successful synthesis of Au nanocrystals under these conditions. In addition, the presence of CDs on the AuNP surface can be clearly observed (Fig. 2B and C), and the Raman peak of AuNPs/CDs between 1100 and 1800 cm⁻¹ (Fig. S2^†) also indicates the presence of carbon dots on AuNPs.⁴²Fig. 2D shows the XRD patterns of CDs (black) and AuNPs/CDs (red). There is no diffraction peak for CDs, indicating the amorphous structure of CDs. However, the obvious peaks at 38.9°, 44.8°, 65.1° and 78.1° (red) for AuNPs/CDs, assigned to the diffraction from the (111), (200), (220) and (311) planes, respectively, of fcc Au crystals,⁴³ also prove the successful formation of Au nanocrystals and agree well with the results of TEM. Fig. 2E displays the FT-IR spectra of AuNPs/CDs (red) and CDs (black). Similar groups can also be found on both CDs and AuNPs/CDs, indicating the presence of CDs on the AuNP surface. In a word, the results described above not only prove the successful synthesis of AuNPs, but also the structure of CDs decorated on the AuNP surface based on the in situ carbonization of CPC at room temperature.Open in a separate windowFig. 2(A) TEM and (B) HRTEM images of AuNPs/CDs. (C) The structure of AuNPs/CDs. (D) XRD profiles and (E) FT-IR spectra of CDs (black) and AuNPs/CDs (red).The reduction of 4-NP to 4-AP with an excess amount of NaBH₄ was carried out to quantitatively evaluate the catalytic properties of AuNPs/CDs. In the absence of the catalyst, a strong absorbance peak at 400 nm was observed for the mixture of 4-NP and NaBH₄, which was attributed to the 4-NP ions under alkaline conditions.⁴⁴ After adding the catalysts CDs and AuNPs/CDs into the reaction system, the reduction process was monitored by measuring the time-dependent absorption spectra of the mixed reaction solution. As shown in Fig. 3A, the nearly unchanged absorption even after one hour when only CDs were present as the catalyst indicates the non-active nature of CDs for 4-NP reduction. However, when we used AuNPs/CDs as the catalyst, the absorbance intensity of 4-NP at 400 nm decreased quickly as the reaction time was extended, and this was accompanied by the appearance of an absorbance peak of 4-AP at 300 nm (Fig. 3B), indicating the higher catalytic activity of AuNPs/CDs for the reduction of 4-NP to 4-AP by NaBH₄. This result also indicates that the reduction of 4-NP should be attributed to the catalysis of AuNPs in AuNPs/CDs due to the non-active CDs. It should be noted that the reduction of 4-NP by NaBH₄ could be completed within 10 minutes, with the observation of fading and ultimate leaching of the yellow-green color of the reaction mixture in the aqueous solution. However, a longer reaction time (more than 18 minutes) was required to achieve the full reduction of 4-NP under similar conditions with AuNPs alone (synthesized with trisodium citrate; see ESI^† for preparation details) as the catalyst (Fig. 3C). Fig. 3D shows the absorption changes of the solutions at 400 nm in the presence of different catalysts, and the quicker decrease in absorption indicates the higher catalytic activity of AuNPs/CDs than that of AuNPs. Since the concentration of BH₄⁻ was constant during the catalytic reaction and much higher than that of 4-NP, the rate constants could be evaluated by the pseudo-first-order kinetics using ln(C_t/C₀) = −kt, where k is the apparent first-order rate constant; its value estimated directly from the slope of the straight line can be used to evaluate the catalytic activity of a catalyst.⁴⁵ As shown in Fig. 3E, a good linear relationship of ln(C_t/C₀) versus the reaction time (t) is observed for the two catalysts; the rate constant (k) values were calculated as 1.83 × 10⁻⁴ min⁻¹, 0.11 min⁻¹ and 0.30 min⁻¹ for CDs, AuNPs and AuNPs/CDs, respectively. These results clearly demonstrated the higher catalytic activity of the AuNPs/CDs composites, which was about 2.7-fold higher than that of AuNPs. In addition, the AuNPs/CDs catalyst exhibited better/comparable catalytic activity compared to/to that of previously reported modified gold catalysts in terms of the time needed for the reduction reaction and rate constant (Table S1^†), demonstrating its potential applications in catalysis.Open in a separate windowFig. 3The UV-vis absorption spectra for the reduction of 4-NP by CDs (A), AuNPs/CDs (B) and AuNPs (C). The plots of absorbance (D) and ln(C_t/C₀) (E) versus reaction time for the catalytic reduction of 4-NP based on different catalysts. (F) The mechanism for the enhanced catalytic activity of AuNPs/CDs for 4-NP reduction.Based on the experimental results and analysis mentioned above, the enhanced catalytic activity of AuNPs/CDs for 4-NP reduction should be attributed to the presence of CDs on AuNPs, which leads to a synergistic effect between AuNPs and CDs. This synergistic effect plays an active part in catalysis and therefore enhances the catalytic activity of AuNPs/CDs, which can be explained as follows: as a π-rich molecule, 4-NP can be adsorbed onto the surface of CDs via π–π stacking interactions.^20,23 In addition, the adsorption of 4-NP on AuNPs/CDs can be demonstrated by the decreased absorbance of the 4-NP solution after adding AuNPs/CDs in the presence of NaOH instead of NaBH₄ (Fig. S3^†). This endows AuNPs/CDs with anchoring sites for the adsorption of 4-NP, and such strong adsorption results in a higher concentration of 4-NP near the surface of AuNPs,²⁰ leading to efficient contact between them and therefore speeding up the catalytic process (Fig. 3F(I)). In contrast, for AuNPs without the presence of CDs, 4-NP must collide with AuNPs by chance and must remain in contact for the catalysis to proceed; or else, 4-NP will pass back into the solution and the reaction cannot occur (Fig. 3F(II)) until it reaches the AuNP surface again.⁴⁶ This can also be demonstrated by the increased reaction rate constant for the 4-NP reduction with more catalysts present in the reaction system (Fig. S4^†). In addition, due to the excellent electron acceptor and donor properties of CDs,^47,48 which can obtain/give excess electrons from/to AuNPs (Fig. 3F), like a reservoir of electrons, the electron transfer from CDs to AuNPs increases the local electron concentration and maintains AuNPs in an electron-enriched state,⁴⁹ facilitating the uptake of electrons by the 4-NP molecules.In summary, a nanocomposite of AuNPs/CDs was successfully synthesized via the room-temperature in situ carbonization of CPC as a capping agent for AuNPs. As a catalyst for 4-NP reduction, this composite showed superior catalytic performances to AuNPs, which could be rationally attributed to the enhanced adsorption of 4-NP on CDs providing a high concentration of 4-NP near AuNPs for a more effective reduction of 4-NP. This work not only offers an attractive catalyst material for 4-NP reduction, but also opens an exciting new avenue for the rational design and development of CD/metal nanostructure hybrids for various applications.