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1.
Formation of a new metastable fcc-MgH2 nanocrystalline phase upon mechanically-induced plastic deformation of MgH2 powders is reported. Our results have shown that cold rolling of mechanically reacted MgH2 powders for 200 passes introduced severe plastic deformation of the powders and led to formation of micro-lathes consisting of γ- and β-MgH2 phases. The cold rolled powders were subjected to different types of defects, exemplified by dislocations, stacking faults, and twinning upon high-energy ball milling. Long term ball milling (50 hours) destabilized β-MgH2 (the most stable phase) and γ-MgH2 (the metastable phase), leading to the formation of a new phase of face centered cubic structure (fcc). The lattice parameter of fcc-MgH2 phase was calculated and found to be 0.4436 nm. This discovered phase possessed high hydrogen storage capacity (6.6 wt%) and revealed excellent desorption kinetics (7 min) at 275 °C. We also demonstrated a cyclic-phase-transformation conducted between these three phases upon changing the ball milling time to 200 hours.

Effect of mechanically-induced cold-rolling followed by high energy ball milling on cyclic phase transformation.

The worldwide interest in MgH2 is attributed to the natural abundance of Mg metal, and its capability to store hydrogen up to 7.60 wt% (0.11 kg H2 L−1).1–3 Among the metal hydride family, MgH2 has been considered as a promising candidate for solid-state hydrogen storage.4–6 Despite the attractive properties of MgH2, and the simplicity for producing the compound on an industrial scale at ambient temperature via a reactive ball milling (RBM) technique,7,8 MgH2 is a very stable compound, and possesses slow kinetics of hydrogenation and dehydrogenation under 300 °C.9 Since the 1990s efforts have been made in order to destabilize MgH2 and improve its hydrogenation and dehydrogenation kinetics upon doping with a long list of catalysts.10–15 Most of the used catalysts showed significant enhancement of the kinetics behavior for MgH2, indexed by a decreasing decomposition temperature and a speed-up of its kinetics behavior.16–20 In spite of the beneficial effects obtained upon adding such foreign catalytic agents, they always lead to a dramatic decrease of the hydrogen storage capacity of MgH2.21,22Apart from doping MgH2 powders with catalysts, it has been experimentally demonstrated by some authors that changing the crystal structure of stable β-tetragonal MgH2 phase to a less stable phase of γ-orthorhombic MgH2 led to improve the gas uptake/release kinetics and decrease the hydrogenation temperature without drastic decreasing of the storage capacity.23–26 The β-to-γ phase transformations can be attained via severe plastic deformation (SPD)27 at ambient temperature by different approaches such as high-energy ball milling (HEBM),28 cold rolling (CRing),29 equal channel angular pressing (ECAP),30 and high pressure torsion (HPT).22,31 A common result of these employed techniques is the formation of nanocrystalline phase along with introducing high intensity defects, leading to increase of grain boundaries density. Presence of these defects in the lattice leads to create nucleation points for hydrogenation, where existence of large number of grain boundaries assists fast diffusion pathways for hydrogen.The present work has been addressed in part to study the effect of HEBM on the structure and decomposition properties of CRed MgH2 powders. Moreover, we aimed to investigate experimentally the possibility of formation a new metastable MgH2 phase rather than the reported g-phase and theoretically calculated δ and ε phases32 upon long term of milling.For the purpose of the present study, 5 g Mg (∼80 μm, 99.8 wt%) powder was balanced inside a He gas atmosphere-glove box and sealed together with fifty hardened steel-balls (11 mm in diameter), using ball-to-powder weight ratio as 40 : 1. The vial was then evacuated to the level of 10−3 bar and then filled with 50 bar of H2. The RBM process was carried out at room temperature, using planetary-type HEBM. After 25 hours (h) of RBM, the vial was open inside the glove box to discharge the powders. The powders were charged and sealed in a stainless steel (SUS304) tube (0.8 cm diameter and 20 cm length) inside the glove box. The tube contained MgH2 powders were severely CRed for different number of passes (1 to 200 passes), using two-drum type manual cold roller (11 cm wide × 5.5 cm rollers diameter). The as-CRed powders for 200 passes were then HEBMed under hydrogen gas for different milling time, in the range between 3 h to 50 h. All the samples were characterized by means of X-ray diffraction (XRD) with Cu radiation, field-emission high-resolution transmission electron microscope (FE-HRTEM) equipped with energy-dispersive X-ray spectroscopy (EDS), field emission scanning electron microscope (FE-SEM)/EDS, and differential scanning calorimeter (DSC). The absorption/desorption kinetics were investigated via Sievert''s method in different temperatures under hydrogen gas pressure in the range between 200 mbar to 8 bar.The XRD patterns of MgH2 powders obtained after 25 h of RBM is shown in Fig. 1a. Bragg peaks corresponding to starting hcp-Mg powders were hardly seen and replaced by sharp diffracted lines related to γ- and β-MgH2 phases, as elucidated in Fig. 1a. The SEM observations indicated the powders tendency to agglomerate, forming large aggregates upon CRing for 25 passes (Fig. 2a). Increasing the CRing passes to 200 times led to grain refinement, as implied by the broadening in the Bragg-peaks presented in Fig. 1b. At this stage, micro-bands with thickness of 143 μm were developed as a result of cold working generated during CRing process, as shown in Fig. 2b. The FE-HRTEM image of as-CRed powders for 200 passes indicated the development of lattice imperfections (e.g. stacking faults and deformation twins). This is implying the mechanically-induced SPD, as elucidated in ESI, Fig. S1.†Open in a separate windowFig. 1XRD patterns of MgH2 powders obtained after 25 h of RBMing (a), and then CRed for 200 passes (b). XRD pattern of CRed powders for 200 passes and then HEBMEd for 50 h is presented in (c).Open in a separate windowFig. 2FE-SEM micrographs taken at accelerated voltage of 1 kV of MgH2 powders obtained after 25 h of RBMing and then CRed for (a) 25, and (b) 200 passes.In order to study the effect of HEBM on the stability of cold-rolled MgH2 aggregates, the powders were charged into tool steel vial and ball milled under 50 bar of H2 for different milling time. The XRD pattern of CRed MgH2 powders obtained after 200 CR passes and then HEBMed for 50 h is displayed in Fig. 1c. Obviously, the Bragg peaks corresponding to γ- and β-MgH2 phases were completely vanished and replaced by new Bragg peaks of unreported phase, appeared at scattering angles (2θ) of, 35.034, 40.584, 58.758, 70.115, and 73.868 (Fig. 1c). XRD analysis indicated that this discovered MgH2 phase has face centered cubic structure (fcc) of space group, Fm3̄m(225). The lattice parameter (ao) of this phase, calculated from (111) was 0.44361 nm. The as-synthesized fcc-MgH2 powders had fine spherical particles with sizes distributed in the range between 0.25 μm to 1 μm, as displayed in Fig. 3.Open in a separate windowFig. 3FE-SEM micrograph of MgH2 powders obtained after 25 h of RBM, CRed for 200 passes and finally HEBMed for 50 h.
Peak position, 2θ (degree)Interplanar spacing, d (nm)Miller indexes (h,k,l)Lattice parameter, ao (nm)
35.0340.256121110.44361
40.5840.222292000.44458
58.7580.157132200.44443
70.1150.134213110.44512
73.8680.128292220.44441
Open in a separate windowThe FE-HRTEM image of the as-CRed powders for 200 passes and then HEBMed for 50 h is shown in Fig. 4. The image revealed Moiré fringe image for 3 intimated nanograins. Filtered-fringe images corresponding to Zone I is presented in Fig. 4a. The d-spacing related to fcc-MgH2 (111) was calculated and found to be 0.2559 nm, where the corresponding ao was calculated and found to be 0.4433 nm. These values matches well with the XRD analysis (Fig. 4c, was taken from Zone I and oriented to [001] axis, where the corresponding FFT showed spot-electron diffraction pattern related to fcc-MgH2 (111).Open in a separate windowFig. 4(a) FE-HRTEM image, (b) filtered atomic resolution image of Zone I, and (c) FFT image of MgH2 powders obtained after 25 h of RBM, consequently CRed for 200 passes and finally HEBMed for 50 h. Fig. 5 presents DSC thermograms of MgH2 powders obtained after 25 h of RBM, consequently cold-rolled for 200 passes and then HEBM for different times, as indexed in Fig. 5. The DSC curves for the powders obtained after 25 h of RBM and then cold-rolled only without milling for different passes are shown together in ESI (Fig. S2†).Open in a separate windowFig. 5DSC thermograms of MgH2 powders obtained after 25 h of RBM, consequently CRed for 200 passes and final HEBMed for different milling times (6 h to 50 h). The values related to the peak temperatures for each milling time is elucidated in each curve.The decomposition temperature of the powders obtained after 25 h of RBM (before applying CRing process) was 415 °C (Fig. S2†), and tended to decrease sharply to 361 °C upon powders CRing for 200 passes, as displayed in Fig. S2.† This significant decreasing on the decomposition temperature upon increasing the number of CRing passes was attributed to destabilization of MgH2, yielded from introducing severe plastic deformation to the powders.The XRD pattern for MgH2 powders obtained after 200 CRing passes and then heated in DSC up to 500 °C showed the presence of a single hcp-Mg phase (Fig. S3†). The as-HEBMed of the powders CRed for 200 passes revealed single endothermic events related to the decomposition reaction (Fig. 5).Obviously, the peak temperature of the samples obtained after different milling times shifted monotonically to the low temperature side with increasing the HEBMing time (Fig. 5). After 50 h of milling (single metastable fcc-MgH2 phase), the decomposition temperature was reordered to be 222 °C (Fig. 5). This temperature was far below the corresponding decomposition temperature (361 °C, Fig. S3†) corresponding to as-CRed powders (γ- + β-MgH2 phases) obtained after 200 passes (Fig. S3†).The powders obtained after 50 h of HEBM was annealed in the DSC at 220 °C (just beyond decomposition onset temperature) and at 375 °C (well above the onset decomposition temperature) for 7 min. XRD pattern of the first sample annealed at 220 °C indicated metastable fcc-MgH2-to-stable β-MgH2 phase transformation, as implied by disappearance of fcc-Bragg peaks and the presence of pronounced sharp Bragg lines corresponding to β-MgH2 coexisted with small volume fraction of γ-MgH2 (Fig. 6a).Open in a separate windowFig. 6XRD patterns of the samples obtained after 50 h and then annealed in the DSC for 7 min at (a) 220 °C, and (b) 375 °C for 7 min.FE-HRTEM (Fig. 7a) and NBD (Fig. 7b) analysis of the annealed sample at 220 °C confirmed the presence of γ- and β-MgH2 phases and a complete disappearance of metastable fcc-MgH2, as displayed in Fig. 7a and b, respectively. In contrast, XRD pattern of the sample annealed at 375 °C showed the Bragg peaks of hcp-Mg coexisted with small volume fraction of undecomposed β-MgH2 crystals (Fig. 6b). It can be concluded from the structural and thermal analysis that γ- and β-MgH2 phases tended to transform to a new metastable phase upon CRing for 200 passes followed by HEBMing for 50 h. The obtained metastable fcc-MgH2 phase transformed into more stable phases of γ- and β-MgH2 phases when annealed at 220 °C for 7 min. A complete phase transformation to hcp-Mg was attained upon annealing fcc-MgH2 at 375 °C.Open in a separate windowFig. 7(a) FE-HRTEM, and (b) NBDP of the sample milled for 50 h and then annealed in the DSC at 220 °C for 7 min.Further experiments were conducted to examine the stability of fcc-MgH2 phase against the mechanical deformation generated by HEBMing. The powders obtained after 50 h were continuously milled for 100 h, 150 h, and 200 h. The XRD pattern of the milled powders for 100 h indicated the disappearance of Bragg peaks related fcc-MgH2 phase, which were replaced by diffracted lines related to γ- and β-MgH2 phases as shown in Fig. 8a. This implies the disability of fcc-MgH2 phase to withstand against the shear and impact forces generated by the milling media. Surprisingly, increasing the HEBMing to 150 h led to clear γ- , β-MgH2 to fcc-MgH2 (less stable phase) phase transformation (Fig. 8b). This is indicated by the presence of Bragg peaks related to fcc-MgH2 phase and the disappearance of the diffracted lines corresponding to the MgH2 phases, as displayed in Fig. 8b.Open in a separate windowFig. 8XRD patterns of as-CRed MgH2 powders for 200 passes and then HEBMed for (a) 100 h, (b) 150 h, and (c) 200 h. Fig. 9 presents a schematic illustration of free energy changes of β-γ-fcc MgH2 phases upon increasing HEBM time. Based on the results motivated of the present study, mechanically-induced fcc-MgH2 to γ- and β-MgH2 phase transformation (point 3-to-points 2 + 3) was achieved upon increasing the milling time to 100 h. Introducing severe lattice imperfections to the fcc-phase is proposed to be responsible to insist this metastable phase to gain free energy and hence transformed into a more stable phase, as illustrated in Fig. 9. This phase transformation can be taken place upon annealing the powders via thermally induced phase transformation, as indexed by point 3-to-points 2 + 1 (Fig. 9).Open in a separate windowFig. 9Schematic presentation of free energy changes conducted upon HEBMing CRed MgH2 powders for long term of milling.The obtained γ- and β-MgH2 composite phases were subjected plastic deformation and defects, leading to lose free energy and transformed to the same metastable fcc-MgH2 phase with further milling time (150 h), as denoted by points 1 + 2 to point 3 (Fig. 9). Further increasing the milling time (200 h) led fcc-MgH2 to gain energy and failed into more stable phases of γ- and β-MgH2.Since high-energy ball milling process introduces intensive vacancies, lattice defects, grain boundaries and surfaces, the ball-milled powders can store a large amount of mechanical-strain energy.33,34 Introducing such defects to the crystalline lattice destroys the periodical structure of the stable tetragonal-MgH2 phase, leading to the formation of a less stable phase (fcc-MgH2). Moreover, the present result suggests that the formation enthalpy of the metastable fcc-MgH2 phase is comparable to the γ- and β-MgH2 phases and the energy barrier between these three phases is probably rather low to allow such cyclic-phase transformations. We should emphases that all the results obtained from XRD analysis were used to determine the weight percentage of each phase, using the approaches described by Guan et al.,35 Ma et al.,36 Yu et al.,37 and Cheng et al.38 Fig. 10 displays the dehydrogenation kinetics behaviors of the CRed powder obtained after 200 passes and then HEBMed for 50 h (fcc-MgH2 phase). The measurements were conducted in the temperature range of 175 °C to 275 °C under 200 mbar.Open in a separate windowFig. 10Dehydrogenation kinetics measured for 10 individual samples of MgH2 powders obtained after 25 h of RBM, consequently CRed for 200 passes and then HEBMed for 50 h. The measurements were conducted under 200 mbar H2 (a) without powders activation, and (b) after activated the powders at 300 °C under 10 bar H2.In order to maintain the crystal structure of the powders (fcc-MgH2 phase) obtained after this stage of milling, the desorption kinetics measurements measured without activation for 5 individual samples (Fig. 10a). All samples were successfully desorbed their hydrogen storage with different time scale. Generally, the fcc-MgH2 powders showed advanced dehydrogenation characteristics over γ- and β-MgH2 phases. At 175 °C, the sample desorbed ∼4 wt% H2 within 40 min (Fig. 10a). However, the powders desorbed about 6.5 wt% H2 within 22 min at 200 °C (Fig. 6a). Increasing the applied temperature to 225 °C and 250 °C, improved the dehydrogenation kinetics of fcc-MgH2, indicated by the short time required to desorb 6.6 wt% H2 in 17 min and 10 min, respectively (Fig. 10a).Outstanding desorption kinetics was conducted at 275 °C, when the sample desorbed 6.6 wt% H2 within 7 min, as elucidated in Fig. 10a. We should emphases that the XRD patterns for the examined samples at temperature range laid between 175 °C to 225 °C revealed presence of Bragg peaks corresponding to γ- and β-MgH2 phases. However, the XRD pattern for those samples examined at higher temperatures (250 °C and 275 °C) revealed diffracted lines of hcp-Mg phase. Fig. 10b displays the dehydrogenation kinetics conducted for the same samples shown in 10a, however, they were activated firstly at 300 °C (far above the transformation temperature of fcc-MgH2 to γ- and β-MgH2 phases) under 25 bar H2. Based on this activation step condition, all the samples lost their fcc-structure and completely transformed into γ- and β-MgH2 phases. This led to a significant deduction of dehydrogenation kinetics that become very slow when compared with the same samples shown in Fig. 10a. For example, the sample examined at 175 °C required more than 650 min to desorb less than 5.5 wt% H2 (Fig. 10b). The two samples examined at 200 °C and 225 °C desorbed about 6.4 and 6.6 wt% H2 within 600 and 390 min, respectively (Fig. 10b). Comparing the necessary desorption time (100 min) for the sample examined at 275 °C to release 6.6 wt% H2 (Fig. 10b) with that time required (7 min) for fcc-MgH2 sample (Fig. 10a) to desorb same hydrogen amount at the same temperature, we can realize that the kinetics desorption of fcc-MgH2 phase is 14 time faster than γ- and β-MgH2 phases.  相似文献   

2.
Effect of C-terminus amidation of Aβ39–42 fragment derived peptides as potential inhibitors of Aβ aggregation     
Akshay Kapadia  Aesan Patel  Krishna K. Sharma  Indresh Kumar Maurya  Varinder Singh  Madhu Khullar  Rahul Jain 《RSC advances》2020,10(45):27137
The C-terminus fragment (Val-Val-Ile-Ala) of amyloid-β is reported to inhibit the aggregation of the parent peptide. In an attempt to investigate the effect of sequential amino-acid scan and C-terminus amidation on the biological profile of the lead sequence, a series of tetrapeptides were synthesized using MW-SPPS. Peptide D-Phe-Val-Ile-Ala-NH2 (12c) exhibited high protection against β-amyloid-mediated-neurotoxicity by inhibiting Aβ aggregation in the MTT cell viability and ThT-fluorescence assay. Circular dichroism studies illustrate the inability of Aβ42 to form β-sheet in the presence of 12c, further confirmed by the absence of Aβ42 fibrils in electron microscopy experiments. The peptide exhibits enhanced BBB permeation, no cytotoxicity along with prolonged proteolytic stability. In silico studies show that the peptide interacts with the key amino acids in Aβ, which potentiate its fibrillation, thereby arresting aggregation propensity. This structural class of designed scaffolds provides impetus towards the rational development of peptide-based-therapeutics for Alzheimer''s disease (AD).

Amidated C-terminal fragment, Aβ39–42 derived non-cytotoxic β-sheet breaker peptides exhibit excellent potency, enhanced bioavailability and improved proteolytic stability.

First reported by Alois Alzheimer in 1906, Alzheimer''s Disease (AD) is a progressive, neurodegenerative disorder with an irreversible decline in memory and cognition.1 It is commonly seen in elderly populations and is marked by two major histopathological hallmarks, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT).2 The number of patients suffering from AD has been increasing at an alarming rate. It is estimated that around 60 million patients will be suffering from AD by the end of 2020 and half of this patient population would require the care equivalent to that of a nursing home.3 Even after a century of its discovery, there has been no treatment that targets the pathophysiology of AD.4 The current treatment regimen includes acetylcholine-esterase inhibitors (AChEI) comprising of donepezil, rivastigmine and galantamine as well as N-methyl-d-aspartate (NMDA)-receptor antagonist, memantine. These provide only symptomatic relief to the patient. Most of the therapeutics that are currently being tested in clinical trials couldn''t proceed beyond phase II and phase III clinical trials due to lower efficacy in elderly patients, multiple side effects and limitations in their pharmacokinetic and pharmacodynamic profiles.5–9 This has created challenges on the societal and economic upfront.Literature analysis reveals that the soluble oligomeric Aβ species is the culprit for neurotoxicity. It interrupts normal physiological functioning of the human brain. The central hydrophobic fragment Aβ16–22 (KLVFFAE) and the C-terminus region fragment Aβ31–42 (IIGLMVGGVVIA) are responsible for controlling the aggregation kinetics of the monomeric species, wherein the later still remains relatively less explored.8,9 Our group is focused on development of peptidomimetic analogues for preventing Aβ aggregation. Studies on a complete peptide scan on the C-terminus region regions has already been published previously.10–12 In an attempt to enhance the biological efficacy of the previously designed scaffolds,12 we rationalized the use of sequential amino acid scan by modifying/replacing individual residues, as well as amide protection of the C-terminus on the lead tetrapeptide sequence (Val-Val-Ile-Ala) to enhance the proteolytic stability of the peptides.C-terminus amidated peptides were synthesized by microwave-assisted Fmoc-solid phase peptide synthesis protocol. Scheme 1 shows the general route for the synthesis of peptides employing Rink amide resin (detailed methodology is mentioned in the ESI, Section 1†). These peptides were characterized using by analytical HPLC, 1H and 13C NMR, APCI/ESI-MS and HRMS.Open in a separate windowScheme 1Synthesis of tetrapeptide 12c using MW-assisted Fmoc-solid phase peptide synthesis protocol employing Rink amide resin. Reaction conditions: (i) 20% piperidine in DMF (7 mL), MW (40 W), 60 °C, 2 cycles – 1.5 & 3 min; (ii) 2, 4, 6, 8 (4 equiv.), TBTU (4 equiv.), HoBt (4 equiv.), DIPEA (5 equiv.), DMF (3.5 mL), MW (40 W), 60 °C, 13.5 min; (iii) TFA : TIPS : H2O (95 : 2.5 : 2.5), rt, 2.5 h; reaction monitoring was done by: UV measurement: Fmoc deprotection-dibenzofulvene adduct, Kaiser test: 1° amines; acetaldehyde test: 2° amines.Aggregation of Aβ42 results in accumulation of toxic species, which interact with neurons and hinder their functioning, leading to loss of memory and cognition. Inhibiting the process of Aβ42 aggregation would alleviate the neurotoxicity imparted in PC-12 cells; this was evaluated by MTT cell viability assay.13 Viability of untreated cells is considered 100%. Upon treatment with 2 μM of Aβ42, only 74% cells were found to be viable. Out of the total tested peptides, seven tetrapeptides 12a, 12c, 12f, 13e, 14b, 15b and 15f showed complete inhibition of Aβ42-induced toxicity by restoring the cell viability to 100%, at respective concentrations. Results for cell viability assay along with Thioflavin-T fluorescence assay for all the synthesized tetrapeptides has been summarized in No.Test peptide sequenceaMTT cell viability assayThT-fluorescence assayTest peptide concentration range (Aβ42: test peptide)10 μM (1 : 5)4 μM (1 : 2)2 μM (1 : 1)10 μM (1 : 5)4 μM (1 : 2)2 μM (1 : 1)% viable cellsb% inhibitiond11Val-Val-Ile-Ala-OH (lead)93.690.578.966.260.633.911aVal-Val-Ile-Ala-NH282.289.386.452.152.758.812a d -Val-Val-Ile-Ala-NH281.6100.094.882.183.564.712b Phe-Val-Ile-Ala-NH292.195.796.277.666.251.912c d -Phe-Val-Ile-Ala-NH2100.095.298.4100.0100.0100.012d d -Pro-Val-Ile-Ala-NH292.083.582.839.852.960.812e Nva-Val-Ile-Ala-NH283.486.174.170.351.977.212f Aib-Val-Ile-Ala-NH261.395.1100.093.866.064.512g Gly-Val-Ile-Ala-NH275.494.392.198.164.584.413aVal-d-Val-Ile-Ala-NH287.675.274.715.746.589.313bVal-d-Ile-Ile-Ala-NH294.692.890.349.435.165.613cVal-Pro-Ile-Ala-NH283.196.093.018.516.331.813dVal-Aib-Ile-Ala-NH2100.093.075.145.350.052.113eVal-Phe-Ile-Ala-NH293.3100.079.357.261.7100.013fVal-d-Phe-Ile-Ala-NH299.792.994.262.566.275.814aVal-Val-d-Ile-Ala-NH269.676.579.721.825.349.614bVal-Val-Leu-Ala-NH286.3100.083.80.016.542.215aVal-Val-Ile-d-Ala-NH293.880.283.323.214.668.615bVal-Val-Ile-Aib-NH299.1100.071.935.142.024.915cVal-Val-Ile-Gly-NH290.588.580.75.431.862.715dVal-Val-Ile-Val-NH271.775.464.511.06.90.015eVal-Val-Ile-Leu-NH270.671.789.431.230.018.715fVal-Val-Ile-Ile-NH2100.097.078.648.20.00.016a Pro-Pro-Ile-Ala-NH277.760.774.614.218.324.7Aβ4274.05Controlc100.0Open in a separate windowaAmino acid residue modified within the tetrapeptide sequence is indicated in bold.bCell viability studies were performed using MTT cell viability assay against PC-12 cells.cThe percentage of untreated cells was considered 100% (positive control); percentage cell viability was calculated for the cells incubated along with Aβ42 (2 μM) in absence (negative control) and presence of the test peptides in respective dose concentrations for 6 h. % of viable cells was calculated by the formula as 100 × [Aβ42 + test peptide OD570 − Aβ OD570/control OD570 − Aβ OD570]. In a subset of triplicate wells, standard deviation values ranged 1.81–4.72.dInhibition of Aβ42 aggregation was calculated by Thioflavin-T fluorescence assay. % relative fluorescence units (% RFU) exhibited by Aβ fibrils were considered as 100%. ThT dye incubated alone was considered as control and % RFU units were computed when Aβ42 was co-incubated with the test peptides for 24 h (λex 440 nm, λem 485 nm). % inhibition of ThT fluorescence was calculated by using the formula: 100 × [100 − (Aβ42 + test peptide RFU485 − control RFU485/Aβ42 RFU485 − control RFU485)]. In a subset of triplicate wells, SD values ranged 1.22–4.83. Data for both the experiments was recorded for triplicate samples and the readings were averaged (<5% variation).The quantitative evaluation of β-sheet structures within the amyloid fibrils is accessed by the fluorescence of the Thioflavin-T dye.14 Inhibiting amyloid fibrillation would reduce or eliminate such an enhancement in fluorescence. This concept is utilized to evaluate compounds that would prevent Aβ from aggregating.15–17 ThT fluorescence in the presence of Aβ42 alone was considered 100% and % relative fluorescence unit (% RFU) values were calculated for Aβ42 co-incubated with the respective inhibitor peptides. ThT incubated alone, exhibited % RFU of nearly 53.3% as compared to control solution without dye. Complete data of % inhibition of Aβ42 by the test peptides has been summarized in 17 Out of all the tested peptides, peptides 12c and 13e showed minimal enhancement in ThT fluorescence when co-incubated with equimolar concentrations of Aβ42. Peptides 12f and 12g showed >90% activity at five-fold excess dose concentrations. A comparative bar graph representation for the four most active peptides 12c, 12f, 12g and 13e has been depicted in Fig. 1A. To understand the % RFU values indicating the relative fluorescence of ThT and % inhibition exhibited by the most active test peptides 12c, 12f, 12g and 13e, values have been summarized in ESI, Tables S1 and S2.† The observed RFU was close to that of the control wells where the dye incubated alone. Negligible increment of ThT fluorescence when the test peptides are co-incubated with Aβ42 peptide clearly indicates the inhibition of fibrillation. It also provides further support to the inhibition of Aβ42-induced neuronal toxicity as studied in the MTT assay. The % inhibition of Aβ42 aggregation as depicted by the ThT fluorescence assay is in accordance with the % cell viability data obtained by the MTT assay. Exact correlation cannot be established between the two because of the differential behavior of Aβ42 in the presence of a cellular environment as well as the treatment/incubation time for both the experiments.Open in a separate windowFig. 1Effect of most active test peptides on Aβ42 aggregation: bar plots depicting the decrease in % RFU of ThT dye when Aβ42 (2 μM) was co-incubated with test peptides at higher doses (A), and lower doses (B). Complete fluorescence was represented by the Aβ42 peptide incubated along with the dye (black) and dye control (grey) represents the dye incubated alone. Subsequent bars represent Aβ peptide co-incubated with the varying concentrations of inhibitor peptides for 24 h. Significance values indicated with respect to the Aβ peptides, *, p < 0.05; **, p < 0.01; ***, p < 0.001. (C) Dose dependent modulation of Aβ42 aggregation-induced-neurotoxicity in PC-12 cells exhibited by the test peptide 12c (black). (D) Concentration dependent % inhibition on Aβ42 aggregation mediated ThT fluorescence exhibited by the test peptide 12c (black). % inhibition of ThT fluorescence was calculated by using the formula: 100 × [100 − (Aβ42 + test peptide RFU485 − control RFU485/Aβ42 RFU485 − control RFU485)]. Readings (λex 440 nm, λem 485 nm) was recorded for triplicate samples from three individual experiments and the readings were averaged (<5% variation). Error bars represent mean ± SD (n = 3). Data were analyzed by one-way anova test.Peptides 12c and 12f that exhibited >98% cell viability at the lowest tested concentration of 2 μM were then evaluated at lower dose concentrations of 1.0 μM, 0.5 μM and 0.1 μM, against 2 μM of Aβ42 maintaining the ratios of 1 : 2, 1 : 4 and 1 : 20 (test peptide : Aβ42), respectively. The graphical plot of dose dependent modulation of Aβ42 aggregation-induced-neurotoxicity in PC-12 cells is depicted in Fig. 1C. Peptide 12c exhibited 78% inhibition of Aβ42 even at a lowest tested dose of 0.1 μM. A graphical representation of the % decrease in RFU has been depicted in Fig. 1B and dose dependent % inhibition of Aβ42 aggregation has been depicted in Fig. 1D. Excellent activities were exhibited when the test peptide is present in equimolar concentrations of Aβ42, indicating 1 : 1 inhibition of the parent peptide.Upon the basis of careful analysis of data reported herewith and results published earlier,10–12 a correlation between the amino acid residues within the tetrapeptide sequence and the exhibited activity was established. Replacement of the first residue, Val39 with hydrophobic residues (Phe and D-Phe) exhibited >90% inhibition. The replacement of Val40 with hydrophobic (Phe, D-Ile) or conformationally restricted amino acids (Pro, Aib) slightly enhanced the potency of the peptide. This holds true even in dual substitution at Val39 and Val40. Any replacement or modification yielded less active derivatives, indicating Ile41 is critical for activity. Small analogous amino acid is preferred at the Ala42 for retaining the activity. Amidation of the C-terminus results in enhancement of inhibition potential for some peptides. In some cases, a decrease in activity is also observed. A summary of the SAR is shown in Fig. 2. Understanding the sequential positioning of these residues would help us further develop derivatives with enhanced potency to inhibit Aβ42 aggregation.Open in a separate windowFig. 2Derived structure–activity-relationship of tetrapeptides.It is reported that there are two species of Aβ i.e. Aβ40 and Aβ42, present in the diseased brain.18–20 Evaluating the inhibitory activities of the test compounds on the aggregation of both the species would be of biological significance.21 Therefore, inhibitory potential of peptide 12c was evaluated on Aβ40. The relative increase in the ThT fluorescence when Aβ40 was incubated alone for 24 h was very less or similar to that of the control wells containing ThT (Fig. 3A). Further testing for 48 h and 72 h, respectively yielded no substantial results (ESI, Table S3†).Open in a separate windowFig. 3Thioflavin-T fluorescence studies on Aβ species: % RFU exhibiting the effect of peptide 12c on aggregation of (A) Aβ40 (5 μM) and (B) Aβ40 & Aβ42 mixture (5 μM) mediated ThT fluorescence. Complete fluorescence was represented by Aβ40 and the 10 : 1 mixture of Aβ peptides incubated along with the dye (black) and dye incubated alone (grey). Subsequent bars represent the respective concentrations of inhibitor peptide 12c co-incubated with the corresponding Aβ peptides for 24 h. Readings (λex 440 nm, λem 485 nm) was recorded for triplicate samples from three individual experiments and the readings were averaged (<5% variation). Error bars represent mean ± SD (n = 3). Data were analyzed by one-way anova test. Significance values indicated with respect to the Aβ peptides, *, p < 0.05; **, p < 0.01; ***, p < 0.001.The minimal increase in fluorescence could be attributed to the slower nucleation rate and longer lag phase in the kinetics of Aβ40 fibril formation in comparison to Aβ42.22–24 Also, Aβ40 is relatively less neurotoxic and its aggregation propensity enhances in the presence of Aβ42, although the former is present in a ten-fold higher concentration. Thus, evaluation of the inhibitory activity of test peptide 12c on the mixtures of Aβ40 : Aβ42 in the ratio of 10 : 1 was performed. On incubation of a mixture of 5 μM of Aβ40 and 0.5 μM of Aβ42 (ratio of 10 : 1) the % relative increase in ThT fluorescence was comparatively higher than when Aβ40 was incubated alone (Fig. 3B). When compared to that of Aβ42 incubated alone as analyzed in the previous experiments, the fluorescence intensities were less. This gave us a clear indication that the aggregation propensity of Aβ40 is amplified in the presence of 0.1 equimolar Aβ42. On co-incubation of the test peptide 12c with the 5 μM mixture of Aβ40 : Aβ42 in the ratio of 10 : 1, substantial decrease in the fluorescence levels were observed (ESI, Table S4†).As a prophylactic measurement, the potential ability of the test peptides to deform the aggregated Aβ42 was investigated.25,26 Monomeric Aβ42 was pre-incubated for a period of 24 h and fluorescence was measured. As anticipated, there was a marked increase in the fluorescence due the fibril state of Aβ42. Test peptide was added to each of the wells at the respective dose concentrations and readings were recorded at in a time dependent manner until 120 h of incubation. Time dependent % deformation of preformed fibrils in the presence of equimolar test peptide has been depicted in Fig. 4A. It could be observed that peptide 12c has the potential of deforming pre-aggregated Aβ42 fibrils (>35%) until 48 h of incubation. Also, peptide 12c significantly reduced the fluorescence of Aβ42 showing 57.5, 34.9 and 33.7% inhibition at 2, 1 and 0.5 μM, respectively after 24 h treatment. % inhibition and % RFU for time intervals of 24 h and 48 h has been provided in the ESI, Table S5.†Open in a separate windowFig. 4Time dependent inhibition of Aβ42: (A) % deformation or disaggregation of preformed Aβ42 fibrils in presence of equimolar concentration of test peptide 12c as evaluated via ThT fluorescence assay. (B) Time and concentration dependent RFU comparison depicting the effect of individual tetrapeptide 12c on Aβ42 mediated-ThT fluorescence. % inhibition of ThT fluorescence was calculated by using the formula: 100 × [100 − (Aβ42 + test peptide RFU485 − control RFU485/Aβ42 RFU485 − control RFU485)]. Readings (λex 440 nm, λem 485 nm) was recorded for triplicate samples and the values were normalized to the ThT dye control and averaged (<5% variation). Data was interpreted from three individual experiments. Error bars represent mean ± SD (n = 3). Data were analyzed by one-way anova test.A time dependent ThT fluorescence assay was performed on the most active test peptide 12c at the similar concentrations of 2, 1 and 0.5 μM with Aβ42 (2 μM) for a period of 7 days. Readings were recorded at regular time intervals of 24 h each. Fig. 4B shows the decrease in the RFU values when Aβ42 was incubated in presence of peptide 12c. Aβ42 on incubation alone with the ThT dye showed an enhancement in the fluorescence of about 57% that could be attributed to the aggregation of the Aβ42 peptide. The fluorescence shown by the blank wells, wherein the dye incubated alone was considered as the control. Compared to the Aβ42 sample, very low values of fluorescence were observed in the presence of peptide 12c. % inhibition of Aβ42 aggregation exhibited by the test peptide has been summarized in ESI, Table S6.† It can be summed that peptide 12c exhibits activity on preformed Aβ42 fibrils as well as inhibits Aβ42 aggregation until 120 h of treatment.ANS fluorescence assay was performed in complimentary to Thioflavin-T assay.27–29 The effect of test peptide inhibiting the process of Aβ42 aggregation as well as deformation of the preformed Aβ42 fibrils was evaluated. The relative fluorescence for Aβ42 fibrils was considered to be 100% and decrease in the % RFU when test peptides were co-incubated with Aβ42 was computed. The fluorescence emitted by binding of ANS to the test peptide itself was subtracted as the test peptide is hydrophobic. The results for relative decrease in fluorescence obtained in both the sub-experiments have been summarized in Fig. 5A. Upon co-incubation of Aβ42 and test peptide 12c in ratios 1 : 1 and 1 : 0.5, a marked decrease in the fluorescence intensity was observed, in comparison to that of the lowest tested concentration of 0.5 μM. These results are in accordance to the results seen in ThT fluorescence assay.Open in a separate windowFig. 5Additional fluorescence studies: (A) effect of varying concentration of tetrapeptide 12c on inhibition of Aβ42 fibril formation (Set 1) and on pre-aggregated fibrils of Aβ (Set 2). Complete fluorescence was represented by the Aβ42 (2 μM) incubated alone, monomeric (Set 1) and pre-aggregated t = 24 h (Set 2) and in the presence of respective concentrations of the test peptide 12c after 24 h. ANS dye incubated alone was considered as control and % RFU units for individual samples were computed by normalizing to the ANS dye control (λex 480 nm, λem 535 nm). Subsequent bars represent the % RFU of the respective concentrations of the inhibitor peptide 12c co-incubated with the differential states of Aβ42 peptide (2 μM) for 24 h. (B) Fluorescence spectrum showing effect of test peptide on Aβ42 aggregation and its interaction with GUVs. Fluorescence of Aβ42 alone at 0 h (green), 24 h (black); along with test peptides 12c (blue) after 24 h in the presence of GUVs (λex 480 nm, λem 400–600 nm). ANS dye incubated alone was considered as control and relative FL. Intensities for individual samples were computed by normalizing to the ANS dye control. (C) Intrinsic tyrosine fluorescence of Aβ42 during fibrillation and inhibition by test peptide 12c (λex 260 nm, λem 280–410 nm). Fluorescence of 5 μM Aβ42 (t = 0 h, green), 5 μM Aβ42 incubated alone (t = 24 h, black), Aβ42 co-incubated along with 5 μM of the test peptides, 12c (t = 24 h, blue). Readings was recorded for triplicate samples from three individual experiments and were averaged (<5% variation). Error bars represent mean ± SD (n = 3). Data were analyzed by one-way anova test.It is hypothesized that the aggregated soluble oligomeric form of Aβ42 interacts with the neuronal membranes by hampering cellular processes and exhibiting neurotoxicity.7 The design of the experiment was similar to the MTT test conditions, wherein giant unilamellar vesicles (GUVs) with composition mimicking the rat neuronal myelin were prepared (ESI,† Section 5.1) and interaction of Aβ was evaluated by ANS fluorescence measurements.29–32 When Aβ42 was just added to the prepared GUVs (t = 0 h), ANS showed a good emission spectrum from 450 to 550 nm. After 24 h incubation of Aβ with the vesicles, no emission band was seen, indicating the absence of hydrophobic binding domain, thus no fluorescence.This could be attributed that the hydrophobic region entered the vesicles, providing no binding site for the dye. Emission intensities obtained for the vesicles alone was considered as blank and was subtracted from the readings obtained for both the time points. To evaluate the effects of incubation of test peptides and its inhibitory effect on Aβ42 aggregation, Aβ42 and test peptide 12c along with the GUVs was incubated for 24 h at 37 °C and the relative change in the fluorescence was observed. Readings for the test peptide incubated alone with the vesicles at the similar concentration were subtracted the final readings so as to obtain a comparable result for Aβ. On co-incubation of Aβ42 with 12c, two distinct observations were seen, primarily a visible emission spectrum and secondly a blue shift with a slight increase in the emission intensity (Fig. 5B). The emission spectrum indicates that the hydrophobic region was available for binding to ANS, thus indicating that Aβ was available in its monomeric form itself. The increase in emission intensity and the blue shift does suggest certain interactions between 12c and the full-length Aβ, which results into differential binding of ANS to the test peptide–Aβ complex (ESI, Fig. S2†).Monitoring intrinsic Tyr fluorescence of Aβ42 during fibril formation and interaction with most active test peptides was also studied. Tyr has significantly lower quantum yield than Trp and is usually only used as an intrinsic fluorescent probe in Trp-lacking proteins or peptides, since energy transfer to Trp residues usually quenches the Tyr fluorescence. Tyrosine shows a typical emission band at 305 nm, which is red shifted to 340 nm due to resonance of the phenol to phenolate ion. We hypothesized that in aggregated state of Aβ42, stacking of phenolate ions of the tyrosine residues will produce slightly enhanced fluorescence in comparison to that of the monomeric or non-aggregated state. It could be clearly seen, in the overlay of fluorescence spectrum for Aβ42 incubated alone for 0 h (green) and 24 h (black), as well as in presence of 12c (blue, Fig. 5C) that the monomeric state of Aβ42 was retained in presence of the test peptides. A comparative bar plot analysis (ESI, Fig. S3†) of the fluorescence response at 340 nm has been indicated to compare the change in observed fluorescence intensities.Since amyloid-β aggregation is preceded by the conformational transition towards increasing β-sheet structure, monitoring the content of β-sheet formation would therefore depict the effect of inhibitors on the aggregation of Aβ42.32,33 The effect of inhibitor peptides on the conformation of Aβ42 was assessed via CD spectroscopy.34–36 Spectra of equimolar concentrations of the individual test peptides were subtracted from the corresponding spectra of inhibitor peptides co-incubated Aβ42. Predicted values of conformation are summarized in ESI, Table S7.† When incubated alone, Aβ42 exhibited a conformational transition from random coiling and turn to majorly β-sheet form. Initially, Aβ42 peptide majorly comprised of 49.4% β-sheet conformation. At the end of 24 h incubation period, β-sheet content increased to 66.4%, with the α-helix content increasing from 6.3% to 17.0%. In the presence of inhibitor peptide 12c, β-sheet form completely vanished and turns and random coiling was seen to be present in 46.6 and 41.0% respectively. This clearly indicates that 12c inhibits β-sheet formation propensity of Aβ42. The spectral curve obtained for Aβ42 (t = 24 h) shows the presence of a positive maxima at 195 nm (black), clearly indicating the conformation of the peptide in the β-sheet form, is absent in the former that is, Aβ42 (t = 0 h), which clearly exhibits a positive maxima at around 205 nm, indicating larger proportion of turn type conformation to be present. No definitive negative minima on the curve were visible at 217 nm, but the shallow curves in the expanded region were indicative of the presence of smaller proportions of α-helix conformations. In the presence of 12c reduction in β-sheet content can also be visualized by the complete absence of the positive maxima at 195 nm, wherein the spectrum follows the similar pattern to that of the Aβ42 (t = 0 h). The prevention of conformational transition to β-sheet suggests the ability of 12c to inhibit the fibrillation process. The positive curve shifts more towards 200–205 nm, indicating a larger proportion of the peptide to be present in the turn form. These observations coincide to the predicted values by the Yang protocol. The effect of the presence of equimolar concentrations of inactive peptide 13a on the conformational changes on Aβ42 was evaluated. A positive maxima at 195 nm is a clear indicative of higher proportions of β-sheet type of secondary structural conformation to be present. This indicates the inactiveness of the peptide 13a and its inability to prevent aggregation of Aβ42. Self-aggregation potential of peptide 13a deters its potential to inhibit Aβ42 aggregation.A compiled CD spectrum recorded depicting a relative comparison of peptides 12f and 13a, incubated for 24 h at 37 °C in the presence and absence of equimolar concentrations of Aβ42 has been presented in Fig. 6. Spectra of test peptides incubated alone were subtracted to obtain the final spectra for comparing the conformational state of Aβ42. A comparison of the individual CD spectrums of the test peptides incubated alone to that incubated in the presence of equimolar ratio of Aβ42 has been summarized (ESI, Fig. S4†).Open in a separate windowFig. 6Secondary structure analysis using CD: CD spectrum showing the conformational changes on Aβ42 aggregation in the presence of active peptide 12c and inactive peptide 13a. Aβ42 (10 μM) at 0 h (black) and 24 h (blue), co-incubated individually with equimolar ratios inhibitor peptide 12c (green) and inactive peptide 13a (red) for 24 h.To understand the process of inhibition of Aβ42 in presence of 12c, mass fragmentation techniques were employed.37 The MS spectrum of full-length Aβ42 (10 μM) in the presence and absence of an equimolar amount of 12c was recorded. Fig. 7, shows the ESI spectrum for Aβ42 incubated alone (A), along with 12c (B).Open in a separate windowFig. 7HRMS Analysis: ESI-MS for Aβ42 (10 μM) incubated alone (A), in presence of equimolar ratios of test peptide 12c (B) for 24 h.The spectrum for Aβ42 incubated alone shows a major peak at m/z 685.4357, which may be attributed to aggregated Aβ42 depicting higher mass-to-charge ratio. Further peaks at m/z of 788.4373 [(Aβ42)6+], 507.2713 [(Aβ1–9)1+], 958.3161 [(Aβ10–42)7+] and 1308.0646 [(Aβ1–11)1+] represent the Aβ42 monomer and its specific fragments, respectively. Hexameric form of Aβ42 with m/z 2185.4363 [(6Aβ42)13+] is also observed in the spectrum.38 On comparing the spectrum obtained for Aβ42 incubated along with 12c, and that of Aβ42 incubated alone, additional signal peaks were seen. This suggested the occurrence of adduct between Aβ42 and 12c, as these peaks were not analogous to the molecular weight of native Aβ42 or test peptides themselves. Analyzing the interactions of 12c with that of Aβ42, the mass spectrum shows a peak at m/z 471.7321 [(Aβ12–42 + 12c)8+], depicting 1 : 1 covalent interaction with Aβ12–42 fragment of Aβ42. The spectrum also shows signal peaks corresponding to that of Aβ42, seen in the previous spectrum. It was clear from the above spectrum that the test peptide interacts with the monomeric unit of the Aβ42, thereby preventing its aggregation.Visual investigation of the effects of the peptide 12c, on the morphology and abundance of Aβ42 fibrils was performed by high resolution transmission electron microscopy (HR-TEM).39 Shapes and morphology of the fibrils were also examined using scanning transmission electron microscope (STEM).40 Inactive peptide 13a was selected as a negative control. The control sample of Aβ42 incubated alone at t = 0 h, where uniform distribution of smaller particles of Aβ was seen (Fig. 8A, HR-TEM and Fig. 8D, STEM).Open in a separate windowFig. 8Electron microscopy studies: HR-TEM and STEM images depicting the effects of active peptide 12c and inactive peptide 13a on the aggregation of Aβ42. Aβ42 (10 μM) was incubated alone t = 0 h (A and D), t = 24 h (B and E); with equimolar concentrations of inhibitor peptide 12c (C and F); inactive peptide 13a (H and K) as well as peptide 12c (G and J) and inactive peptide 13a (I and L) incubated alone, respectively. (Additional images have been provided in the ESI,† Section 11.3).After an incubation span of 24 h, appearance of amyloid fibrils and an extensive network of long, straw-shaped fibrils were observed (Fig. 8B and E). In the presence of peptide 12c (Fig. 8C and F), only smaller particulate aggregates were seen, indicating complete inhibition of the amyloid fibrils. On co-incubation of Aβ42 with the inactive peptide 13a, large aggregated structures (Fig. 8H and K) were observed. In order to visualize the aggregation of the peptide themselves, equimolar concentrations of peptides 12c and 13a were incubated alone under similar conditions and visualized. Very small granular structures were seen for the 12c (Fig. 8G and J) whereas slightly larger and patchy aggregates were seen for inactive peptide 13a (Fig. 8I and L).In order to evaluate and understand the biosafety and pharmacokinetic profile of the test peptides, cell-cytotoxicity studies employing PC-12 cells was performed. Test peptide were tested up to a highest tested concentration of 20 μM and none of the peptides exhibited undesirable cytotoxicity. Fig. 9A depicts a graphical representation of the % viable cells in presence of 20 μM concentration of peptide 12c.Open in a separate windowFig. 9Cytotoxicity and bioavailability study: (A) analysis of the cytotoxic effects of the peptide 12c (20 mM) on the viability of PC-12 cells evaluated using MTT cell viability assay. The percentage of untreated cells was considered 100% (positive control) and presence of the test peptides in respective dose concentration for 6 h. (B) BBB-permeability of peptide 12c in comparison to 11a, as determined by the PAMPA-BBB assay. Pe was calculated by using the formula VdVa/[(Vd + Va)St] ln(1 − Aa/Ae), where Vd and Va are the mean volumes of the donor and acceptor solutions, S is the surface area of the artificial membrane, t is the incubation time, and Aa and Ae are the UV absorbance of the acceptor well and the theoretical equilibrium absorbance, respectively. Data was recorded for triplicate samples in three individual experiments and the readings were averaged (<5% variation).A major challenge for peptide-based therapeutics is the BBB permeability and proteolytic stability against various enzymes within the body.41In vitro BBB penetration of the most active peptide 12c as well as the lead peptide 11a using parallel artificial membrane permeation assay (PAMPA-BBB) was performed following the previously reported protocols.42–45 The UV/Vis absorptions of both the peptides was recorded after permeating through an artificial porcine polar brain lipid (PBL) membrane and the effective permeabilities (Pe) were calculated. As described in Fig. 9B, the Pe values of the most active peptide 12c was significantly higher than that of 11a, demonstrating enhanced permeability of the modified peptide.Trypsin is the one of the most notorious endopeptidases and cleaves the amide bond next to a charged cationic residue.46 Hence, in order to evaluate whether the synthesized peptides have incorporated the proteolytic stability properties, trypsin and serum stability studies on the peptide 12c was performed. The peptide was incubated with 100-fold excess of trypsin and was subjected to analysis by RP-HPLC. Chromatograms depicted that the peptides exhibited intact integrity, having their retention time unaltered even after 24 h of trypsin treatment. It was observed that, there were no peaks seen before and after the main peak of the peptide indication no fragment and/or other intermediate formation. Superimposed HPLC chromatograms of time point''s intervals have been depicted in Fig. 10A.Open in a separate windowFig. 10Proteolytic stability study: (A) superimposed HPLC chromatograms of most active peptide 12c at time intervals of 0, 2, 4, 8, 12, 18 and 24 h after trypsin treatment; (B) graphical representation showing % degradation for peptide 12c on serum treatment. (C) Mass spectra for peptide 12c at 0, 12, 18 and 24 h of serum treatment. Analyzed by ACD-Mass Fragmenter tool. (D) Predicted susceptible cleavage sites for peptide 12c. Most susceptible peptide bond has been indicated in bold red.Serum stability assay following similar protocol was performed. The chromatograms depicted that the peptides exhibited intact integrity, having their retention time unaltered up to 12 h of serum treatment. The peaks obtained for the peptides at 18 h and 24 h of serum treatment, were comparatively smaller to that of the previous peaks indicating slight degradation of the peptide. Superimposed HPLC chromatogram for peptide 12c has been provided in ESI, Fig. S6.†To calculate the rate of degradation of the peptide on serum treatment, analysis and comparison the area under the curve of the peak of the respective peptide at their specific time intervals.47,48 A comparative analysis depicted that around 20% of the peptide is present after 24 h of serum treatment. Fig. 10B indicates the % degradation of the peptide in serum over a period of 24 h. The initial calculation of % peptide present in the sample aliquot is indicated in the ESI, Fig. S7.† The extrapolated data helped us to determine the degradation rate of the peptide in serum (ESI, Table S8†).48–50 It can be concluded that approximately 50% of the peptide is stable until 12 h of serum treatment, following which it shows an decline in stability decreasing to about 22% until 24 h.In order to study the mode of degradation of the peptide and the susceptibility of the peptide towards peptide degradation, mass spectroscopy was employed. The samples analyzed for peptide content on RP-HPLC were further subjected to LCQ analysis.51,52 At 0 h, the molecular ion peak (m/z 470) of the peptide corresponded to the molecular mass of the peptide itself. Sequential fragmentation pattern was minimal and a clear mass spectrum was seen. After 12 h, multiple fragmentation peaks were seen indicating that the peptide has undergone cleavage at multiple sites. ACD-Mass Fragmenter tool was used to analyze the specific fragmentation pattern. Fig. 10C summarizes the mass spectrums and shows the specific fragmentation pattern. Based on the fragmentation pattern for the tetrapeptide sequence, the most susceptible bonds that could easily undergo cleavage were identified. ACD Mass Fragmenter tool was used to understand the peptide fragmentation pattern. Fig. 10D depicts the structure of the peptide 12c indicating the most susceptible peptide bond. This understanding provides impetus in site specific modification in improving the stability of the peptides.Computationally understanding the binding mechanism and intra-residual interactions of the test peptides with the single monomeric as well as the proto-fibrillar unit of Aβ42 would prove to be useful. Various structures for the both the forms of Aβ42 are reported in the literature. A monomeric sequence bearing complete sequence of all 42 amino acids residues was used (PDB Id: 1IYT; ESI, Fig. S8†). The structure comprises of α-helices and random coiling, similar to the data previously reported.53 A proto-fibrillar unit comprising of 6 full length spatially arranged in a ‘S’ shaped manner recently reported by Colvin and co-workers54 (PDB Id: 2NAO, ESI, Fig. S10†) was used for understanding the interaction of the test peptides on the proto-fibrillar unit of Aβ. Reactive site analysis of the pre-optimized framework of the monomeric Aβ42 showed that the hinge region is the most prone to aggregation due to the presence of reactive residues in that particular segment (Maestro, Bioluminate suite; ESI Fig. S9†). To understand the interaction of the test peptide with the full-length Aβ42, a grid incorporating the whole sequence was generated. Docking studies were performed with the peptides mentioned in this work along with a few molecules reported in literature10–12,55,56 for comparative analysis of the binding modes and interactions.57–59 Docking, glide and residual interaction energy scores for the molecules selected from literature and test peptides from the current study are summarized in ESI (Tables S9 and S10†). Although the analysis of the scores reveal that similar docking and glide scores were seen in both the cases. The energy of interaction of the test peptides with the monomeric unit proved to be a comparable factor to that of the literature reported ligands (ESI Table S11†).Test peptides have shown to interact with Glu11, His13, His14, Gln15, Phe19, Phe20 and more specifically with Asp23. These residues are involved to aid the aggregation of monomeric Aβ42 into the fibrillar species, as also seen in reactive residue analysis (ESI, Fig. S11†). Binding of the test peptides to these residues, block the free interaction of these residues to others, inhibiting their aggregation propensity. Ligand interactions of the most active test peptide 12c with the monomeric unit, their respective ligand interaction diagrams (2D and 3D) have been summarized in Fig. 11A and B. The interaction energies are in accordance to those exhibited by the standard ligands indicating similar kind of interactions and thus reinforcing the results of studies carried out in this work. A structural framework 2NAO-06 of proto-fibrillar Aβ42 was rationalized to be the most optimal structure and was prepared for docking studies (ESI, Fig. S10†). Since it is a proto-fibrillar unit, the most reactive sites for the binding were identified. SiteMap Analysis feature identified 5 ligand-binding sites (ESI, Fig. S12†). The predicted sites did coincide with the predicted reactive residues, thus indicating certain interactions between those residues and the ligand to be feasible, which would inhibit the process of aggregation. To carry out docking studies, receptor grids at the predicted sites on the proto-fibrillar unit was generated. Since there has been no docking studies performed using 2NAO as the protein, validation of the use of 2NAO and the predicted sites, by docking standard ligands was performed (ESI, Tables S12 and S13†). Analysis of the docking studies revealed SiteMap-2 to be the most plausible site for action of an inhibitor. The molecule can interact with the residues that aid in aggregation. This would block the further attachment of another monomeric unit to the site-recognition units on the proto-fibrillar structure. Subsequent interaction with the neighboring residues of both the chains destabilizes the preformed bonds, which hold the adjacent units together.Open in a separate windowFig. 11 In silico study: ligand interaction diagram showing interactions of the ligand with the residues of monomeric unit 1IYT-10 (A and B) and with the proto-fibrillar unit 2NAO-06 (C and D). 3D representation (Left) showed along with 2D representation (Right).Docking studies of the peptides presented in this work was carried out and docking scores and the residue interaction energies obtained for the set of synthesized tetrapeptides for SiteMap-2 has been summarized in ESI, Table S14.† On careful analysis it can be seen that interaction with Met35, Val36, Gly37 of chain D, as well as Glu11. His13, His14 and Gln15 of the neighboring chain A, show that the test peptide does interact with both the neighboring chains and especially with those amino acids that are solely responsible for maintaining the dimeric structure of the proto-fibrillar unit. To have a clear understanding of the interactions, ligand interaction diagrams for the test peptide 12c, depicting its interaction with the specific residues of the proto-fibrillar unit have been summarized in Fig. 11C and D.  相似文献   

3.
Correction: Rapid synthesis of internal peptidyl α-ketoamides by on resin oxidation for the construction of rhomboid protease inhibitors     
Tim Van Kersavond  Raphael Konopatzki  Merel A. T. van der Plassche  Jian Yang  Steven H. L. Verhelst 《RSC advances》2021,11(15):8897
  相似文献   

4.
Correction: Efficient removal of cobalt from aqueous solution using β-cyclodextrin modified graphene oxide     
Wencheng Song  Jun Hu  Ying Zhao  Dadong Shao  Jiaxing Li 《RSC advances》2019,9(70):40975
Correction for ‘Efficient removal of cobalt from aqueous solution using β-cyclodextrin modified graphene oxide’ by Wencheng Song et al., RSC Adv., 2013, 3, 9514–9521.

The authors regret that Fig. 1 and ​and33 were incorrect in the original article. The SEM images of both GO and β-CD, and the Raman spectra of both, were confused with other samples. The correct versions of Fig. 1 and ​and33 are presented below.Open in a separate windowFig. 1SEM images of (a) GO and (b) β-CD-GO.Open in a separate windowFig. 2Raman spectra of GO and β-CD-GO.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.  相似文献   

5.
Preparation and characterization of an edible metal–organic framework/rice wine residue composite     
Teer Ba  Chenyang Shen  Xiaoshan Zhang  Chang-jun Liu 《RSC advances》2022,12(23):14639
In this communication, using rice wine residue (RWR) as the support, an edible γ-cyclodextrin-metal–organic framework/RWR (γ-CD-MOF/RWR) composite with a macroscopic morphology was synthesized. The obtained edible composite is promising for applications in drug delivery, adsorption, food processing, and others.

An edible metal–organic framework/rice wine residue composite was made with large surface area for potential applications in drug delivery, adsorption, food processing, and others.

As a typical class of porous materials, metal–organic frameworks (MOFs) have attracted increasing attention since being first proposed by Yaghi and co-workers.1 Over the past two decades, owing to their large surface area, ultrahigh porosity and tunable pore size,2 MOFs have exhibited great prospects for gas storage and separation,3,4 catalysis,5–8 sensors,9 drug delivery,10–12etc. Among numerous reported MOFs, γ-cyclodextrin-MOF (γ-CD-MOF), which is connected by the (γ-CD)6 units of alkaline earth metal ions, was initially synthesized and reported by Stoddart et al.13,14 in the 2010s. Owing to the –OCCO– groups derived from γ-CD, this kind of MOF is edible and therefore opens a new path for preparing green, biocompatible and edible MOF materials.13,15,16 For example, Stoddart et al.11 reported a co-crystallization approach to trap ibuprofen and lansoprazole inside γ-CD-MOF, and the resultant composite microspheres can be used for sustained drug delivery. Zhang et al.17 proposed a strategy to graft cholesterol over the surface of γ-CD-MOF to form a protective hydrophobic layer to improve its water stability. Many researchers succeeded in preparing oral delivery medicine with high drug loading and an enhanced therapeutic effect by combining the drug molecules with γ-CD-MOF.16,18–20 These works present the excellent application prospects of γ-CD-MOF in the medical field.Since MOFs possess so many attractive advantages, extensive studies have focused on combining MOFs with many other functional materials (metal nanoparticles, quantum dots, carbon matrices and polyoxometalates, etc.) by means of the synergistic effect, leading to the formation of novel composites designed for targeted applications.21–28 However, these reported composites were still presented as loose powders, which may not be convenient for the applications. Therefore, the question of how to prepare MOFs-based composites for larger particles at low cost is of great significance. On the other hand, as a traditional alcoholic beverage, rice wine has been popular in southern China and some other Asian nations for thousands of years.29 The rice wine lees or rice wine residue (RWR) is a by-product of the fermentation process of rice wine. It is a mixture of proteins, amino acids and polysaccharides. It is traditionally a health food in some Asian nations.30 The edibility, extensive source, low cost and specific macroscopic shape make RWR a potential functional material for further use of MOFs.Herein, a facile and environmental-friendly strategy has been developed to realize the growth of γ-CD-MOF on rice wine residue, resulting in the formation of an edible MOF/RWR composite in the shape of rice grains. The material characterization confirmed the obtained composite possesses the characteristics of MOF. Except for the edible γ-CD-MOF/RWR, other MOF/RWR composites (HKUST-1, ZIF-67 and MIL-100(Fe)/RWR composites; shown in Fig. S1†) were prepared to demonstrate the universality of this synthesis strategy.The synthesis procedure of the γ-CD-MOF/RWR composite is schematically illustrated in Fig. 1. The rice wine residue was soaked in deionized water for 12 h and then washed with deionized water three times before vacuum freeze-drying. Similar to the synthesis of γ-CD-MOF powder,15 KOH was dissolved into water. Then certain amounts of the aforementioned dry rice wine residue were soaked into the K+-containing solution for 2 h in order to absorb the sufficient potassium ions. K+ was then linked by the coordination of –OCCO– units in γ-CD and RWR with the three-dimensional interconnected network. After vapor diffusion of MeOH and some other procedures described in the synthesis of γ-CD-MOF powder (seen in ESI), the γ-CD-MOF/RWR composite (Fig. 2) was obtained. This method is convenient as no extra binders are needed during the whole process. The same procedure was employed to prepare the RWR composites with other MOFs (HKUST-1, ZIF-67 and MIL-100(Fe)). And the syntheses are briefly described in the ESI. The images of the obtained composites are shown in Fig. S1.†Open in a separate windowFig. 1Schematic illustration of the synthesis procedure of γ-CD-MOF/RWR composite.Open in a separate windowFig. 2Digital photo of the γ-CD-MOF/RWR composite.The rice wine residue, of which the elemental analysis is shown in Table S1,† is mainly composed of polysaccharides and proteins. Thus, a broad peak at around 22.2° in the XRD patterns of rice wine residue can be observed (Fig. S2†), which is due to its poor crystallinity.31 The XRD patterns of γ-CD-MOF and γ-CD-MOF/RWR composite samples are shown in Fig. 3a. The characteristic peaks at 5.6°, 6.9°, 13.3°, 16.6°, 20.6° and 23.2°, observed from the XRD patterns of γ-CD-MOF, agree with the previously reported works.32,33 Meanwhile, compared with γ-CD-MOF, the γ-CD-MOF/RWR composite shows similar characteristic peaks with lower intensity, indicating a lower crystallinity of the MOF within the composite. Fig. 3b shows the FT-IR spectra of different samples. Compared with the rice wine residue, the peaks in regions 1 and 2 of γ-CD-MOF and γ-CD-MOF/RWR can be ascribed to the stretching vibration of –CH2 and –C–O–C– of the MOF, respectively.15,34 These results further confirm the formation of the γ-CD-MOF in the γ-CD-MOF/RWR composite.Open in a separate windowFig. 3XRD patterns (a) and FT-IR spectra (b) of γ-CD-MOF/RWR composite, γ-CD-MOF and RWR.The SEM images were collected to further investigate the micromorphology of the as-prepared samples. As shown in Fig. 4a, a three-dimensional layered network structure and rich macropores of the rice wine residue rough surface can be seen. γ-CD-MOF (Fig. 4b) exhibits a uniform body-centered cubic shape with an average size of 4.27 μm, which is in accordance with the reported works.15,35,36 Meanwhile, the images of the γ-CD-MOF/RWR composite (Fig. 4c and d) show that the cubic γ-CD-MOF crystals are well dispersed on the surface of the rice wine residue and even partially integrated into the framework of the rice wine residue. Compared with the pristine γ-CD-MOF, some γ-CD-MOF in γ-CD-MOF/RWR is not an intact cubic structure, exhibiting a significantly different morphology. This suggests a synergistic effect between the MOF crystals and the rice wine residue during the growth of MOF crystals, rather than a simple physical mixture of the two materials. The thermal stability of the γ-CD-MOF/RWR composite was investigated via TGA analysis. As shown in Fig. S3,† the decomposition temperature of γ-CD-MOF/RWR composite slightly increased compared with those of pristine γ-CD-MOF and rice wine residue. Moreover, the γ-CD-MOF/RWR composite was stable in water, methanol and ethanol (shown in Fig. S4†) even under mild stirring. These results indicate an improved physiochemical stability of γ-CD-MOF after the incorporation of rice wine residue. This finding further confirms the synergistic effect between them.Open in a separate windowFig. 4SEM images of rice wine residue (a), γ-CD-MOF (b) and γ-CD-MOF/RWR composite (c and d). Fig. 5a shows the nitrogen sorption isotherms of the γ-CD-MOF and γ-CD-MOF/RWR composite. Both pristine γ-CD-MOF and γ-CD-MOF/RWR exhibit typical type-I isotherms, demonstrating their microporous structures. The pore size distributions of pure γ-CD-MOF and γ-CD-MOF/RWR (Fig. 5b) confirm the existence of micropores (between 1 and 2 nm). The calculated Brunauer–Emmett–Teller (BET) surface areas, micropore volume and total pore volume are listed in 35,37 The specific surface area of the γ-CD-MOF/RWR composite is 651 m2 g−1, which is significantly higher than that of the pure rice wine residue (10.8 m2 g−1). Thus, the increase in the specific surface area of γ-CD-MOF/RWR composite can be attributed to the growth of γ-CD-MOF on the RWR support. Therefore, γ-CD-MOF/RWR composite inherits both the high porosity of γ-CD-MOF and the macroscopic morphology of rice wine residue, which should contribute to its practical applications.Open in a separate windowFig. 5N2 adsorption and desorption isotherms (a) and pore size distributions (b) of γ-CD-MOF/RWR composite and corresponding comparative samples.Summary of the BET areas (SBET), micropore volume (Vmicro) and total pore volume (Vtot) of γ-CD-MOF, γ-CD-MOF/RWR composite and pure rice wine residue
Samples S BET (m2 g−1) V micro (cm3 g−1) V tot (cm3 g−1)
γ-CD-MOF10960.390.51
γ-CD-MOF/RWR composite6510.220.28
RWR10.80.0240.038
Open in a separate windowTo further investigate the universality of this synthesis strategy, different MOFs (i.e., HKUST-1, ZIF-67 and MIL-100(Fe)) and their corresponding composites were prepared and investigated. Digital photos of different samples (Fig. S1†) show that all composites maintain the original shape of rice wine residue. Meanwhile, the colours of composites vary with different MOFs. Moreover, the XRD results in Fig. S5–S7† confirm the growth of various MOFs on rice wine residue. Therefore, these results demonstrate that this synthesis strategy is universally applicable. Moreover, compared to other MOF-based composites, it should be noted that the composites synthesized via this strategy exhibit a macroscopic shape rather than being a loosely packed fine powder. Considering the industrial demand for enhanced mass transfer with low pressure drop, the MOF/RWR composites are promising for industrial applications.In conclusion, a facile and environmental-friendly method has been developed to prepare a γ-CD-MOF/RWR composite without extra binders. The edibility of γ-CD-MOF and rice wine residue has been well demonstrated in the literature,16,38–42 demonstrating that the γ-CD-MOF/RWR composite is also edible. The growth of γ-CD-MOF on rice wine residue is based on the synergetic effect between the two components, rather than a simple physical mixture of two materials. Due to the large pore size and high BET specific surface area, the edible γ-CD-MOF/RWR composite in the shape of rice will be more convenient for applications including drug delivery, food processing, adsorption, gas separation, catalysis and others. The MOF/RWR composites can be also an excellent precursor for carbon-based material or catalysts.30 The synthetic method developed here might give inspiration for designing and preparing MOF-based composites in the shape of rice with the utilization of RWR.  相似文献   

6.
A julolidine-fused anthracene derivative: synthesis,photophysical properties,and oxidative dimerization     
Zeming Xia  Xiaoyu Guo  Yanpeng Zhu  Yonggen Wang  Jiaobing Wang 《RSC advances》2018,8(24):13588
We describe the synthesis and characterization of a julolidine-fused anthracene derivative J-A, which exhibits a maximum absorption of 450 nm and a maximum emission of 518 nm. The fluorescent quantum yield was determined to be 0.55 in toluene. J-A dimerizes in solution via oxidative coupling. Structure of the dimer was characterized using single crystal X-ray diffraction.

A julolidine fused anthracene derivative with unique photophysical and redox properties was presented.

Julolidine1 is a popular structural subunit in various fluorescent dyes (Chart 1).2 The restricted motion and strong electron-donating capability of the fused julolidine moiety are quite effective for improving the photophysical properties. For instance, julolidine-fused fluorophores normally display desirable photophysical characteristics, such as high quantum yield, red-shifted absorption and emission, and good photostability. Recently, julolidine derivatives have been widely exploited in various applications such as sensing,3 imaging,4 and nonlinear optical materials.5 Several julolidine dyes have been used in dye-sensitized solar cells due to their large π-conjugated system and the promising electron donating property.6Open in a separate windowChart 1The structure of julolidine, J-A and DAA.In this paper, we report a julolidine-fused anthracene derivative J-A, which exhibits attractive photophysical properties not observed in DAA, a dimethyl-amino substituted analogue. Both the absorption and emission of J-A show a dramatic red-shift (ca. 74 and 131 nm, respectively), compared with the unmodified anthracene (Fig. 2). The fluorescence quantum yield of J-A was determined to be 0.55 in toluene, while the emission of DAA was completely quenched. The observed spectral properties were rationalized by DFT calculations. In addition, we found that J-A was stable in the solid state, but reactive in solution. J-A dimer was formed through oxidative coupling at the para-position of the N-atom in a dichloromethane solution under air atmosphere. The structure of the dimerized product was characterized using single crystal X-ray diffraction, which unambiguously reveals the structural feature of the julolidine-fused anthracene compound. Preparation of J-A is shown in Scheme 1. Detailed synthesis and characterizations are provided in the ESI.†Open in a separate windowScheme 1Synthetic route of J-A.Open in a separate windowFig. 2(A) Absorption spectra of J-A, AN, and DAA (1 × 10−4 mol L−1 in dichloromethane); (B) emission spectra of J-A, AN, and DAA (1 × 10−5 mol L−1 in dichloromethane). Excitation wavelength: 350 nm. 1 cm cuvette was used in both of the experiments. Inset: visualized fluorescence in solution was shown. 1H-NMR signals of J-A shift to the high-field significantly, compared with DAA (Fig. 1), which indicates that the fused structure of J-A facilitates electron delocalization from the nitrogen atom to the anthracene moiety, and thus resulting in a stronger shielding effect. In the case of DAA, however, electron delocalization from the dimethyl amino group to the anthracene core is essentially inhibited due to steric hindrance, which will explain the fact that it displays a spectral feature similar to that of the unmodified anthracene.Open in a separate windowFig. 1Comparison of the 1H-NMR spectrum between J-A and DAA in CDCl3. Partial resonance signals in aromatic region are shown.Fusing with julolidine will exert significant effects on the photophysical properties of anthracene. The absorption and fluorescence spectra of J-A, DAA, and anthracene are shown in Fig. 2. The maximum absorption of J-A is 450 nm, which displays a red-shift of about 70 nm compared with the unmodified anthracene. J-A emits green light (maxλem = 518 nm, Φ = 0.55), while anthracene emits blue light (maxλem = 380 nm, Φ = 0.22). In contrast, the absorption of DAA essentially overlaps with that of anthracene, with only a minor red shift of ca. 10 nm, but its fluorescence is quenched significantly (Fig. 2). This spectral feature indicates that the dimethyl amino group is electronically separated from the anthracene moiety in the ground state, a result in good accordance with the 1H-NMR data shown above. The quenched fluorescence of DAA may result from the photo-induced electron transfer7 from the lone pair of the nitrogen atom to the anthracene moiety in the excited state.The observed photophysical properties of J-A were reproduced by DFT calculations. The HOMO and LUMO orbitals are evenly distributed over the anthracene moiety and the N-atom in the julolidine, indicating the existence of a conjugated structure. The HOMO–LUMO transition (f = 0.10) corresponds to the absorption band at 450 nm. The sharper absorption at 390 nm can be assigned to the HOMO to LUMO + 1 transition. In contrast, the HOMO and LUMO orbitals of DAA resemble those of anthracene, because the dimethyl-amino group is orthogonal to the conjugated π-system (Fig. 3).Open in a separate windowFig. 3Molecular orbitals of J-A and DAA calculated at the B3LYP/6-31G(d) level of theory (iso value = 0.02). Orbital energies were given in parentheses. Excitation energies were computed by TD-DFT at the same level. Values in parentheses represent the oscillator strengths (f).J-A is stable in the solid state, but reactive in solution. The cyclic voltammetry (CV) diagram of J-A shows an irreversible oxidation potential at 0.007 V (vs. Fc/Fc+), indicating that J-A is easy to be oxidized (Fig. S3†). Single crystals suitable for X-ray diffraction study were obtained by slow evaporation of a dichloromethane solution of J-A under air atmosphere. To our surprise, instead of J-A, X-ray data discloses the formation of a dimeric product (Scheme 2) of J-A. We hypothesized that the dimeric compound 5 formed via oxidative coupling reaction, a mechanism well-documented for the dimerization of the dimethylaniline compounds.8 The 1H-NMR spectrum of 5 is distinct from that of J-A. All protons of the anthracene part (b′–d′) appear as a group of multiplet resonance signals (6.93–7.04 ppm) (Scheme 2). In addition, mass spectrometric analysis indicates that two hydrogen atoms were removed after the dimerization of J-A. Compound 5 exhibits a maximum absorption at 460 nm and a very weak emission (maxλem = 530 nm, Φ = 0.03, Fig. S1†). Two quasi-reversible oxidation waves were identified in the CV diagram of 5 at −0.010 V and 0.135 V (vs. Fc/Fc+), respectively (Fig. S5†).Open in a separate windowScheme 2Oxidative dimerization of J-A. Inset: partial 1H-NMR of 5 is shown.X-ray structure of 5 is shown in Fig. 4. The two connected anthracene planes are found to be orthogonal to each other with a dihedral angle of 90.17°, as a result of steric repulsion. Specifically, the bond length of N–C3 is 1.389 Å, which is similar to those of the other reported julolidine compounds (1.359–1.393 Å), while significantly shorter than that of the dimethyl-amino anthracene (1.433 Å).9 This result testifies the presence of electron delocalization between the fused julolidine nitrogen and the anthracene π-plane, which is in good agreement with the DFT calculations (Fig. 3). However, the two anthracene π-planes connected by the single bond (C4–C5, 1.489 Å) might not exhibit electron delocalization because of the orthogonal conformation. The fused julolidine ring-i and -ii are symmetric to each other, and both of them adopt an “envelope” conformation. The fused julolidine is nonplanar (bond angle, C3–N–C2, 115.73°, C3–N–C1, 115.92°, C1–N–C2, 113.81°). 5 is closely packed in the crystal (Fig. 4B), and no intercalated solvent molecules were observed. The closest distance between two adjacent anthracene planes is 3.922 Å, indicating a weak π–π stacking. Detailed crystal data are summarized in Table S5.†Open in a separate windowFig. 4(A) Single crystal X-ray structure of 5. (B) View along a-axis.In summary, we report the synthesis and characterizations of a julolidine-fused anthracene derivative J-A, which demonstrates significantly red-shifted absorption (maxλab = 450 nm) and emission (maxλem = 518 nm, Φ = 0.55), compared with the unmodified anthracene. The photophysical properties of J-A also contrast dramatically with a dimethyl-amino analogue DAA, which were rationalized by DFT calculations. In addition, J-A could be transformed into 5, a dimeric product, whose single crystal X-ray structure unambiguously confirmed the structural feature of the julolidine-fused anthracene.  相似文献   

7.
Preparation of a mimetic and degradable poly(ethylene glycol) by a non-eutectic mixture of organocatalysts (NEMO) via a one-pot two-step process     
S. Moins  P. Loyer  J. Odent  O. Coulembier 《RSC advances》2019,9(68):40013
  相似文献   

8.
Correction: Surface hardness and flammability of Na2SiO3 and nano-TiO2 reinforced wood composites     
Edita Garskaite  Olov Karlsson  Zivile Stankeviciute  Aivaras Kareiva  Dennis Jones  Dick Sandberg 《RSC advances》2019,9(58):34086
  相似文献   

9.
Correction: Chemoselective and one-pot synthesis of novel coumarin-based cyclopenta[c]pyrans via base-mediated reaction of α,β-unsaturated coumarins and β-ketodinitriles     
Behnaz Farajpour  Abdolali Alizadeh 《RSC advances》2022,12(14):8547
Correction for ‘Chemoselective and one-pot synthesis of novel coumarin-based cyclopenta[c]pyrans via base-mediated reaction of α,β-unsaturated coumarins and β-ketodinitriles’ by Behnaz Farajpour et al., RSC Adv., 2022, 12, 7262–7267, DOI: 10.1039/D2RA00594H.

The authors regret that an incorrect version of Fig. 4 was included in the original article. The correct version of Fig. 4 is presented below. The CCDC number was also incorrectly cited for this same compound (compound 3d) and should instead be cited as 1970237.Open in a separate windowFig. 1ORTEP diagram of 3d (CCDC 1970237).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.  相似文献   

10.
Cryostorage of unstable N-acetylglucosaminyltransferase-V by synthetic zwitterions     
Tetsuya Hirata  Takahiro Takekiyo  Yukihiro Yoshimura  Yuko Tokoro  Takeru Ishizaki  Yasuhiko Kizuka  Kosuke Kuroda 《RSC advances》2022,12(19):11628
We report biocompatible materials for cryostorage of unstable proteins such as cancer-related enzyme, N-acetylglucosaminyltransferase-V (GnT-V). GnT-V activity and the amount of protein after freezing were better retained in synthetic zwitterion solutions than in the glycerol solution. This study highlights the potential utility of synthetic zwitterions as novel cryoprotectants.

We report biocompatible materials for cryostorage of unstable proteins such as cancer-related enzyme, N-acetylglucosaminyltransferase-V (GnT-V).

Asparagine-linked glycosylation (N-glycosylation) is the most common glycosylation found on cell surfaces, and it plays critical roles in regulating protein folding, stability, and activity.1–3 Mature N-glycans have two to five N-acetylglucosamine (GlcNAc) branches in mammals.2,4 One of these branches, β1,6-GlcNAc, is synthesised by N-acetylglucosaminyltransferase-V (GnT-V)5 (Fig. S1†) and is deeply involved in the aggravation of cancer. For example, it has been shown that tumour growth and metastasis are highly inhibited in GnT-V deficient mice.6 Another study showed that colorectal cancer patients have a poor prognosis when their tumour cells highly express GnT-V.7 Mechanistically, the β1,6-GlcNAc branch promotes cell proliferation through oncogenic signalling from epidermal growth factor receptors.8 In addition, the β1,6-GlcNAc branch on N-cadherin enhances cell migration and invasion.9 These studies suggest that research on GnT-V contributes to cancer therapeutics. Recently, we and others solved the crystal structure of human GnT-V,10,11 allowing us to design novel inhibitors of GnT-V activity for use in cancer therapeutics. Furthermore, the activity of chemically synthesised erythropoietin protein was enhanced when bearing a β1,6-GlcNAc branched N-glycan because of stabilisation in the bloodstream of mice.12 This suggests that GnT-V is potentially applicable to the development of medicines.However, the progress of research on GnT-V and its medical usage has been critically delayed because of the difficulty in long term storing purified GnT-V. Recombinant proteins, including GnT-V, are usually unstable and must be stored in deep freezers. The problem is that cryostorage in water or buffers generally denatures proteins, and thus a combination use of protein cryoprotectants is necessary.13 Although glycerol is the most common protein cryoprotectant,13,14 unfortunately, its protein stabilizing ability was insufficient for GnT-V (described below), and the development of novel cryoprotectants is necessary.We focused on artificial zwitterions (ZIs) to develop a novel protein stabiliser applicable to cryostorage.15–17 Artificial ZIs are analogues of ionic liquids (ILs) but have positive and negative charges in the same ion structures. Fujita et al. and we have previously reported that ZI solutions do not denature proteins such as cytochrome c even at high concentrations.18–20 ZIs have organised bound water structures and enable the renaturation of proteins.18,19,21 We also have reported that the cell toxicity of artificial ZIs is lower than that of dimethyl sulfoxide, which is generally used for biological and medical research, and can be used for cryostorage of animal cells.22,23 Therefore, we hypothesised that ZIs have protein-stabilizing potential under cryostorage of unstable proteins, especially GnT-V.In this study, we selected the ZI, OE2imC3C (Fig. 1), which exhibits enzyme compatibility and the cryoprotective ability for cells.20,22,23 Two more artificial ZIs, VimC3S and C1imC3S,23 were also utilised to investigate the effect of different zwitterionic structures on the ability (Fig. 1), because additional ZIs can be synthesised at a lower cost than expensive OE2imC3C.24Open in a separate windowFig. 1Schematics of artificial zwitterions (ZIs) used in this study.We first examined GnT-V activity in each cryoprotectant solution before freezing. GnT-V activity in a 20 vol% glycerol solution was slightly lower than that in water. This is not caused by the negative effect of glycerol on the GnT-V activity because the activity per protein did not decrease as shown below (see Fig. 4). However, activity in the OE2imC3C and C1imC3C solutions did not decrease, and a slight but non-significant increase was observed (Fig. 2A). Notably, the activity in the 5 and 10 wt% VimC3S solutions was significantly higher than that in water. An increase in enzymatic activity in another IL-containing solution has been reported,25 and this may be the case. Although the mechanism of this increase is unclear, and further analyses are needed to elucidate the precise mechanisms, we speculate that the ion interactions between ZIs and the surface charges of GnT-V possibly affect the structure of GnT-V. This might reduce fluctuations in the GnT-V structure, resulting in the stabilisation of GnT-V, strengthening the interaction with the glycan substrate with its catalytic pocket and the surrounding residues.26 This presumably supports the results that the other two ZIs (OE2imC3C and C1imC3S) also increase the activity. We believe that the increased activity is certain because the ZIs increase the viscosity of the solutions17 and therefore decrease in activity if they are to merely maintain the activity.Open in a separate windowFig. 2Effect of ZIs on GnT-V activity. (A) Quantification of GnT-V activity in various solutions before and after freezing. Error bars represent the standard deviation (SD) (n = 3). Statistics were calculated using a one-way ANOVA post-hoc Dunnett test. *p < 0.05; ***p < 0.0005. (B) Ratio of GnT-V activity after freezing to before freezing. Error bars represent SD (n = 3). Statistics were calculated using a one-way ANOVA post-hoc Tukey test. *p < 0.05; **p < 0.005; ***p < 0.0005.Open in a separate windowFig. 4GnT-V activity per protein amount was calculated based on Fig. 2A and ​and3B.3B. The values were normalised by those in water before and after freezing.We then investigated GnT-V activity after freezing. GnT-V activity was decreased to approximately 30% by freezing in water (Fig. 2A and S2†), demonstrating that GnT-V is prone to inactivation by freeze stress. Even so, a typical cryoprotectant, 20 vol% glycerol, was not sufficiently effective for GnT-V because the residual activity was just approximately 50% after freezing (Fig. 2B). In contrast, GnT-V activity in OE2imC3C and VimC3S solutions was retained much higher even after freezing (residual activity: 68–76%, Fig. 2B). The cryoprotective ability resulted in 1.5-fold activity after freezing in the OE2imC3C and VimC3S solutions, compared to the glycerol solution (Fig. 2A).The ZIs were concentrated at sub-zero temperatures as the water freezes. The concentrated ZIs were not frozen at −80 °C and might protect GnT-V from physical damage by ice crystals. For example, in the case of the 5 wt% OE2imC3C solution, 8 wt% (5 wt% of OE2imC3C and 3 wt% water) did not crystallise even at −100 °C (Fig. S3†). The unfrozen portion formed a glass transition at −85 °C, but it was unclear whether the unfrozen portion was glass or liquid. From these results, ZIs, especially OE2imC3C and VimC3S, are effective cryoprotectants for GnT-V. The cryoprotection efficiency of C1imC3S was lower than that of the other ZIs but still higher than that of glycerol.Freeze stress potentially affects the structure of GnT-V, resulting in aggregation, precipitation, and adsorption to e.g., plastic tubes. Therefore, we next investigated whether ZIs stabilised GnT-V. Consequently, the amount of GnT-V in the solutions before and after freezing was determined by electrophoresis with Coomassie brilliant blue (CBB) staining (Fig. 3A). The residual amount of GnT-V in water substantially decreased to 28% after freezing, and that in 20 vol% glycerol, it was 42% (Fig. 3B). The residual amount of GnT-V in the OE2imC3C and VimC3S solutions was similar to or even higher than that in the glycerol solution (45–55%). These results indicate that ZI stabilises GnT-V by preventing aggregation and/or adsorption to plastic tubes. C1imC3S was not as efficient from this viewpoint, supporting the relatively low cryoprotective effect (Fig. 2).Open in a separate windowFig. 3Stability of GnT-V protein after freezing. (A) CBB staining of purified GnT-V before and after freezing in the indicated solutions. GnT-V protein is indicated by an arrow. Asterisks indicate non-specific bands derived from VimC3S. (B) Upper and middle rows indicate the amount of GnT-V protein before and after freezing, respectively. Protein amount was calculated from the standard curve generated from band intensities of bovine serum albumins. The bottom row indicates the residual amount of GnT-V (percentages of GnT-V protein level after freezing to that before freezing).ZI-derived bands were detected in the 5 and 10 wt% VimC3S solutions (Fig. 3A). The same bands were also detected when using the protein-free VimC3S solution (Fig. S4†), indicating that they were derived from the interaction between VimC3S and CBB. The polymerisation of VimC3S during electrophoresis or its pretreatment (heating at 95 °C for 5 min), based on the vinyl group, is possibly the reason, but further investigation is required. The amount of GnT-V might be overestimated by overlap with the VimC3S-derived band.We calculated the ratio of residual GnT-V activity (shown in Fig. 2) to the residual protein amount (Fig. 3) after freezing. The value was 1.2-times higher in the 20 vol% glycerol solution than in water, which was at most 1.6-times higher in the OE2imC3C and C1imC3S solutions (Fig. 4). The values in the VimC3S solutions were not so high (∼1.2 times), presumably because the GnT-V amount might not be accurately quantified because of the VimC3S-derived band. We can find a clue to possible explanations on the significant increase in our study. We have previously reported the activity of chicken lysozymes in an IL of ethylammonium nitrate (EAN) aqueous solution.27 EAN partly denatures, but the lysozyme partly renatured after freezing and thawing because of the EAN–lysozyme interaction. We speculate that the same phenomenon occurred in this study: (1) the GnT-V protein we obtained was a mixture of natural and partly denatured ones, and ZIs renatured the structure of the latter only; and (2) ZI-stabilised the GnT-V protein and activated it.Finally, we further investigated the effect of ZIs on protein structures from a physical-chemical aspect by using representative OE2imC3C, which showed good effects on both GnT-V activity and protein stability (Fig. 2 and ​and3).3). However, unfortunately, a sufficient amount of GnT-V protein was not obtained because of low expression in cells and aggregation during culture and/or purification. Instead, we selected α-lactalbumin (α-Lac) as a model protein for the following reasons. The structural features of α-Lac are similar to those of GnT-V, as the α-helix and β-sheet contents are similar to those of GnT-V (the α-helix and β-sheet content: 45% and 9% for α-Lac; 43% and 17% for GnT-V, respectively). Moreover, both proteins have high contents of Leu and Lys residues, and the positions of these residues are similar, being that the Leu residues are located in the interior, whereas the Lys residues are on the surface (Fig. S5†). These features guarantee the structural similarity between GnT-V and α-Lac. Furthermore, α-Lac is a relatively unstable protein, as estimated from its free energy,28 although most commercially available proteins are stable for freezing, indicating that α-Lac is potentially vulnerable to freeze stress. The structural change in α-Lac was analysed using Fourier transform infrared (FTIR) spectroscopy (Fig. 5A). In the second derivative FTIR spectra of α-Lac in D2O before freezing, a sharp peak at 1640 cm−1 derived from α-helix29 was observed (Fig. 5B). It shifted to 1645 cm−1 after freezing, which corresponded to the signal of an unfolded state, confirming the unfolding of α-Lac by freezing in D2O. In sharp contrast, OE2imC3C maintained its peak at 1640 cm−1, even after freezing. The FTIR spectra of the 20 wt% OE2imC3C before and after freezing were almost identical. Therefore, OE2imC3C exhibited a cryoprotective effect, at least through the protection of the α-helix, resulting in a higher residual activity of GnT-V after freezing.Open in a separate windowFig. 5Normalised FTIR (A) and their second derivative spectra (B) in the amide I′ region of bovine α-lactalbumin (10 mg mL−1) in aqueous solutions with OE2imC3C (0, 10, and 20%) before (red line) and after (blue line) freezing. The unfolded state was induced by 6 M 1-butyl-3-methylimidazolum thiocyanate ([bmim][SCN]).The ZIs achieved cryostorage of unstable GnT-V. Interestingly, the addition of ZIs slightly enhanced the activity, even before freezing. Moreover, the residual activity after freezing in ZI solutions was 1.6-times higher than that frozen in water. Given that it was 1.2-times in the 20 vol% glycerol solution, a general cryoprotecting solution, ZIs have the potential to be novel cryoprotectants. The ZIs, especially OE2imC3C and VimC3S, prevented protein aggregation and/or adsorption on plastic tubes at least by protecting the α-helix structure.Generally, commercially unavailable proteins purified by researchers are unstable. Although utilization enzymes in the ZI solutions may not be an option now, it will be an option because activation and storage of vulnerable enzymes is critical for the life sciences and utilization of the ZI solution in vitro does not cause any problem. Therefore, we believe that ZIs will be key materials for accelerating the life sciences. The modification of ZI structures may facilitate the generation of ideal cryoprotectants of proteins. It is important to elucidate the generality of the cryoprotective effects of ZIs on protein stability in the future. Moreover, GnT-V activity was significantly increased in the ZI solutions before freezing, indicating their potential use as chemical chaperones, such as therapeutics for neurodegenerative diseases caused by protein misfolding.  相似文献   

11.
Inter- and intramolecular excimer circularly polarised luminescence of planar chiral paracyclophane-pyrene luminophores     
Nobuyuki Hara  Motohiro Shizuma  Takunori Harada  Yoshitane Imai 《RSC advances》2020,10(19):11335
Two types of planar chiral [2,2]paracyclophane-pyrene luminophores (1 and 2) with different binding positions of the fluorescent pyrene units were synthesised. (R)/(S)-1 with 1-pyrene units exhibited green intermolecular excimer circularly polarised luminescence (CPL) at 530 nm in the KBr-pellet, but exhibited no CPL signal in dilute CHCl3 solution. In contrast, (R)/(S)-2 with 2-pyrene units exhibited a blue intramolecular excimer CPL at 450 nm in CHCl3 solution. This is the first example of using the binding position of pyrene and the external environment to tune the type (inter- or intramolecular) and chiroptical sign of excimer CPL.

Two types of planar chiral [2,2]paracyclophane-pyrene luminophores (1 and 2) with different binding positions of the fluorescent pyrene units were synthesised.

Right- and left-handed circularly polarised luminescence (CPL) with a high quantum yield (ΦF) and dissymmetry factor (g value) from enantiopairs of chiral luminescent materials has attracted considerable attention.1 Planar chiral [2,2]paracyclophane is a robust chiral skeleton that is useful for introducing π-conjugation into small and macromolecules. The Morisaki and Chujo groups have synthesised π-stacked chiral molecules based on [2,2]paracyclophane that exhibit CPL with high dissymmetry factors and high quantum yields.2 In contrast, Ema and co-workers reported intense excimer CPL from chiral quaternaphthyls containing four to eight pyrene units linked by ester groups.3Recently, we reported that the non-classical CPL sign of chiral binaphthyl-pyrene organic luminophores with the same axial chirality could be controlled by changing the binding position of pyrene and selecting a specific linker between the chiral binaphthyl and fluorescent pyrene units or by introducing a binaphthyl unit with the opposite chirality.4 These chiral pyrene luminophores exhibited intramolecular excimer CPL in both solution and the solid state.The aim of this work was to develop a novel CPL control system for switching between intra- and intermolecular excimer CPL in planar chiral paracyclophane-pyrene luminophores. For this purpose, we prepared two types of planar chiral paracyclophane-pyrene luminophores ((R)/(S)-1 and (R)/(S)-2) with different binding positions of the fluorescent pyrene units (Scheme 1). In 1 with a 1-pyrene unit, no CPL was observed in dilute CHCl3 solution, but green intermolecular excimer CPL at 510 nm occurred in the KBr-pellet. Constractingly, 2 with a 2-pyrene unit exhibited strong light blue intramolecular excimer CPL at 452 nm in dilute CHCl3 solution but no CPL in the KBr-pellet.Open in a separate windowScheme 1Synthesis of planar chiral paracyclophane-pyrene luminophores with different binding positions of pyrene fluorophores [(R)/(S)-1 and (R)/(S)-2]. DPTS: 4-(N,N-dimethylamino) pyridium-4-toluene sulfonate, DIPC: diisopropylcarbodiimide.(R)/(S)-1 and (R)/(S)-2 were prepared using (R)/(S)-paracyclophanediol and 1-pyrenecarboxylic acid or 2-pyrenecarboxylic acid, respectively (Scheme 1).We recorded the unpolarised photoluminescence (PL) and CPL properties of (R)/(S)-1 and (R)/(S)-2 in CHCl3 solution. As shown in Fig. 1(a), 1 with fluorescent 1-pyrene units does not exhibit a clear CPL signal in dilute CHCl3 solution (1.0 × 10−4 M), although monomer PL is observed with a maximum emission wavelength (λem) of 393 nm.Open in a separate windowFig. 1CPL (upper) and PL (lower) spectra of (a) (R)-1 (blue) and (S)-1 (red), and (b) (R)-2 (blue) and (S)-2 (red) in CHCl3 solution (1.0 × 10−4 M, λex = 340 nm for 1 and 322 nm for 2, path length = 1 mm, 25 °C).Interestingly, paracyclophane-pyrene luminophore 2 with fluorescent 2-pyrene units emitted clear CPL at a maximum CPL wavelength (λCPL) of 452 nm, as shown in Fig. 1(b). This strong signal corresponded to excimer CPL derived from intramolecular π–π stacking of pyrenes, as the CPL band was similar in dilute and concentrated CHCl3 solutions (1.0 × 10−5 and 1.0 × 10−3 M) (Fig. S10 and S12†). The CPL capability was evaluated quantitatively using the equation gCPL = ΔI/I = (IL − IR)/[(IL + IR)/2], where IL and IR are the output signal intensities for left- and right-handed circularly polarised light, respectively, under unpolarised photoexcitation conditions. The |gCPL| value at λCPL = 452 nm is 6.0 × 10−3 with an absolute PL quantum yield (ΦF) of 0.17%. The PL decay of (R)-2 in CHCl3 solution at 460 nm (Fig. S18†) consists of three dominant components (τ1 = 6.99 µs (20.4%), τ2 = 15.3 µs (61.8%), and τ3 = 1.02 µs (17.8%)). This finding indicates that at least three emissive species are responsible for the CPL at the π → π* transition of pyrene. These results suggest that simply changing the bonding position of the fluorescent pyrene units allowed switching of the CPL properties in the solution state.We next recorded the circular dichroism (CD) and UV-vis absorption spectra to study the ground-state chirality of 1 and 2 in CHCl3 solution (1.0 × 10−4 M). Both (R)/(S)-1 and (R)/(S)-2 exhibited obvious mirror-image first Cotton effects at 390 and 339 nm, respectively, as shown in Fig. 2. The CD intensity originating from the ground-state chirality is known as the Kuhn''s anisotropy factor and is theoretically defined as the dissymmetric factor: gCD = (ΔεL − εR) = 2(εL − εR)/(εL + εR). The |gCD| value for the first Cotton CD band is 0.58 × 10−3 at 390 nm for 1 (Fig. 2(a)) and 2.5 × 10−3 at 339 nm for 2 (Fig. 2(b)). This difference shows that the pyrene units in 1 and 2 are in different chiral environments in the solution state.Open in a separate windowFig. 2CD (upper) and UV-vis absorption (lower) spectra of (a) (R)-1 (blue) and (S)-1 (red), and (b) (R)-2 (blue) and (S)-2 (red) in CHCl3 solution (1.0 × 10−4 M, path length = 1 mm, 25 °C).To investigate the HOMOs and LUMOs of the luminophores, we calculated the optimised structures using density functional theory (DFT) at the B3LYP/6-31G (d,p) level in the Gaussian 09 program.5 The optimised structures and the HOMOs/LUMOs of (R)-1 and (R)-2 are shown in Fig. 3. In 1, the HOMO is located on both the pyrene and paracyclophane units, and three vibronic UV bands (0–0′, 0–1′, and 0–2′) were calculated at 376, 373, and 371 nm by using time-dependent density functional theory (TD-DFT) at the B3LYP/6-31G (d,p) level in the Gaussian 09 program,5 respectively. On the contrast, the HOMO and LUMO in 2 are mainly located on the pyrene units, and three vibronic UV bands (0–0′, 0–1′, 0–2′) were calculated at 344, 328, and 314 nm, by using TD-DFT as same as 1, respectively. These values are similar to the experimental results, which suggests that the maximum absorption wavelength results from exciton coupling of the HOMO–LUMO π–π* electronic transition of two pyrene units.Open in a separate windowFig. 3DFT-optimised structures and HOMOs/LUMOs of (R)-1 and (R)-2 at the B3LYP/6-31G (d,p) level of theory.Subsequently, we studied the CPL behaviour of both (R)/(S)-1 and (R)/(S)-2 in the solid state (Fig. 4). Surprisingly, paracyclophane-pyrene luminophore 1 with fluorescent 1-pyrene units emitted strong green CPL at 510 nm in the KBr-pellet, even though no CPL was observed in dilute CHCl3 solution. The weak CPL spectrum observed in concentrated CHCl3 solution (1.0 × 10−3 M) showed the same emission bands as in the KBr-pellet (Fig. S7†). This result indicates that the green CPL is excimer emission derived from the intermolecular π–π stacking of pyrenes in the solid state. The |gCPL| value at the maximum CPL wavelength (513 nm) was 3.9 × 10−3 and the ΦF value was 0.03. The PL decay of (R)-1 in the solid state at 510 nm consisted of three components (τ1 = 3.84 µs (11.7%), τ2 = 19.0 µs (80.5%), and τ3 = 0.3 µs (7.83%)) (Fig. S17†). Thus, at least three emissive species are responsible for the CPL properties at the π → π* transition of pyrene.Open in a separate windowFig. 4CPL (upper) and PL (lower) spectra of (a) (R)-1 (blue) and (S)-1 (red), and (b) (R)-2 (blue) and (S)-2 in the KBr-pellet (λex = 388 nm for 1 and 344 nm for 2, 25 °C).On the contrast to 1, paracyclophane-pyrene luminophore 2 with fluorescent 2-pyrene units exhibited no clear excimer CPL in the KBr-pellet, although monomer PL was observed at 440 nm.To study the ground-state chirality in the KBr-pellet, the CD and UV-vis absorption spectra of (R)/(S)-1 and (R)/(S)-2 were recorded, as shown in Fig. 5. In the KBr-pellet, opposite CD signals were observed for (R)/(S)-1 and (R)/(S)-2. As in solution, a negative Cotton effect was observed for (R)-1 and a positive Cotton effect was observed for (R)-2 despite the two luminophores having the same chiral skeleton. The |gCD| values of the first Cotton band were 0.18 × 10−3 at 390 nm for 1 and 1.2 × 10−3 at 339 nm for 2. This result shows that the ground-state chirality of the pyrene units in 1 and 2 are different in the KBr-pellet. However, for either 1 or 2, the ground-state chiral environments of the pyrene units are similar in both CHCl3 solution and the KBr-pellet.Open in a separate windowFig. 5CD (upper) and UV-vis absorption (lower) spectra of (a) (R)-1 (blue) and (S)-1 (red), and (b) (R)-2 (blue) and (S)-2 in the KBr-pellet at 25 °C.Based on these results, it is thought that in 1, which bears fluorescent 1-pyrene units, the two pyrene units cannot form an intramolecular excimer chiral configuration in the photoexcited state in solution; however, in the photoexcited state in the solid state, two pyrene units on different molecules can form an intermolecular excimer chiral configuration. Constratingly, in 2, which bears fluorescent 2-pyrene units, the two pyrene units can form an intramolecular excimer chiral configuration in the photoexcited state in solution, but two pyrene units on different molecules cannot form an intermolecular excimer chiral configuration in the photoexcited state in the solid state. This switching of the CPL characteristics is considered to arise from the difference in the orientation of the two pyrene units in 1 and 2.In summary, we designed two types of planar chiral paracyclophane-pyrene luminophores. The CPL properties of these luminophores depended on the binding position of the fluorescent pyrene units. Compound 1 with 1-pyrene units showed green intermolecular excimer CPL in the KBr-pellet despite exhibiting no CPL in dilute CHCl3 solution. In contrast, 2 with 2-pyrene units showed light blue intramolecular excimer CPL in CHCl3 solution but no CPL was observed in the KBr-pellet. This is a first report of clear switching of intra- or intermolecular excimer CPL by changing the binding position of fluorescent pyrene units.  相似文献   

12.
Asymmetric total synthesis of four bioactive lignans using donor–acceptor cyclopropanes and bioassay of (−)- and (+)-niranthin against hepatitis B and influenza viruses     
Ryotaro Ota  Daichi Karasawa  Mizuki Oshima  Koichi Watashi  Noriko Shimasaki  Yoshinori Nishii 《RSC advances》2022,12(8):4635
The asymmetric total synthesis of four lignans, dimethylmatairesinol, matairesinol, (−)-niranthin, and (+)-niranthin has been achieved using reductive ring-opening of cyclopropanes. Moreover, we performed bioassays of the synthesized (+)- and (−)-niranthins using hepatitis B and influenza viruses, which revealed the relationship between the enantiomeric structure and the anti-viral activity of niranthin.

The total synthesis of four lignans including (−)- and (+)-niranthin has been achieved utilizing cyclopropanes. Based on bioassays of the (+)- and (−)-niranthins using HBV and IFV, we speculated the bioactive site of niranthin against HBV and IFV.

Lignans are attracting considerable attention due to their widespread distribution in plants and their varied bioactivity.1–5 For example, matairesinol,2 dimethylmatairesinol,3 yatein,4 and niranthin5 are found in nature and exhibit e.g., cytotoxicity,2b,d,3b,4b anti-bacterial,2c anti-allergic,3c anti-viral,4d,5b,e anti-leishmanial,5d and strong insect-feeding-deterrent activity.4c Among these compounds, anti-viral compounds have received significant attention owing to the worldwide pandemic of coronavirus disease 2019 (COVID-19). Although niranthin exhibits anti-viral activity toward the hepatitis B virus (HBV),5b,e the enantiomeric SAR (structure–activity relationship) for the anti-viral activity of niranthin has not been revealed so far. To examine the SAR for a pair of enantiomers, an independent asymmetric synthesis of both enantiomers is necessary. However, the alternative synthesis of (−)- or (+)-niranthin has not been reported.6 During our recent studies on the transformation of cyclopropanes,7 we have reported a reductive ring-opening of enantioenriched donor–acceptor (D–A) cyclopropanes and its application to an asymmetric total synthesis of yatein.7i As a further extension of this synthetic method, we disclose here the asymmetric total synthesis of (−)-dimethylmatairesinol, (−)-matairesinol, (+)-niranthin, and (−)-niranthin. Moreover, the results of bioassays using (+)-niranthin and (−)-niranthin against HVB and influenza virus (IFV) are described (Scheme 1).Open in a separate windowScheme 1Some examples of bioactive dibenzyl lignans. Scheme 2 outlines the enantioselective synthesis of optically active lactones 5a and 5b. Following our previous report,7i we attempted to synthesize the enantio-enriched bicyclic lactones 4a and 4b.Open in a separate windowScheme 2Enantioselective synthesis of key intermediates 5a and 5b.Initially, the cyclopropanation of enal 1 with dimethyl α-bromomalonate 2 using the Hayashi–Jørgensen catalyst afforded the desired optically active cyclopropylaldehydes 3a and 3b in good to high yield with high ee.7c,e,h–j,8,9 The reduction of the aldehydes to alcohols and subsequent lactonization with p-TsOH afforded lactones 4a and 4b in high yield with high ee. The optical purity of lactones 4a and 4b were determined using HPLC analyses on a chiral column, and the ee values of the enantioselective cyclopropanations were estimated based on these HPLC analyses. Next, treatment of bicyclic lactones 4a and 4b with hydrogen in the presence of a catalytic amount of Pd–C in AcOEt at 0 °C resulted in a regioselective reductive ring-opening to furnish benzyloxylactones 5a and 5b in good to high yield with high dr and high ee. In the hydrolysis step, debenzylation of the benzyloxyaryl group did not occur under these mild conditions, i.e., in AcOEt at 0 °C.7iFor the α-benzylation of 5a and 5b to afford 6a–c, the corresponding substituted benzylhalides were necessary. 3-Methoxy-4-benzyloxybenzylbromide and 3,4-dimethoxybenzylbromide were easily prepared by known methods (for details, see the ESI†); however, the preparation of 3,4-methylenedioxy-5-methoxybenzylbromide (16) required a modified procedure that involves the regioselective protection of the hydroxy group at the 3-position of 3,4,5-trihydroxybenzene (Scheme 3). The methylenedioxylation of gallic acid (10) during the first step resulted in a low yield of 11.10 Consequently, we successfully synthesized 12 using a cyclic boron-ester system.11 Arylmethylbromide 16 was derived from ester 12 in two steps in good to high yield.Open in a separate windowScheme 3Preparation of substituted benzylbromide 16.Next, enolates were generated from lactones 5a and 5b using K2CO3 in DMF, and successfully attacked the benzylhalides on the less-hindered side to afford α-benzyl lactones 6a–c with excellent dr values (Scheme 4).7i,12 The trans-α,β-disubstituted lactones 7a–c were obtained via the hydrolysis of the α-methoxycarbonyllactones 6a–c followed by decarboxylation. The transformation from the enol form to the keto form gave the thermodynamically favored trans products (7a–c) with excellent dr values.7i,12 Finally, the debenzylation of 7a using a catalytic amount of Pd–C in methanol under a hydrogen atmosphere afforded matairesinol (7d) in 96% yield. Thus, the total syntheses of dimethylmatairesinol (7b) and matairesinol (7d) were achieved, and spectral data of these natural products were consistent with reported data.2e,3d The absolute configuration of these compounds were determined using the known data of optical rotation values. The reduction of lactone 7c using LAH afforded diol 8 in 91% yield (Scheme 4). Subsequent dimethylation of the resulting diol 8 using NaH and MeI furnished (−)-niranthin in 89% yield with 95% ee.13 Spectral data of (−)-niranthin was also consistent with reported data.5b,e,6 Following the total synthesis of (−)-niranthin, we also achieved the total synthesis of (+)-niranthin via an alternative enantioselective cyclopropanation using a different enantiomeric Hayashi–Jørgensen catalyst derived from d-proline instead of l-proline (Scheme 5).14Open in a separate windowScheme 4Alternative asymmetric total synthesis of dimethylmatairesinol, matairesinol, and (−)-niranthin.Open in a separate windowScheme 5Alternative asymmetric total synthesis of (+)-niranthin.(−)-Niranthin has been reported to exhibit anti-HBV activity.5b,e Aiming to shed light on the relationship between its enantiomeric structure and activity, we performed a bioassay on the synthesized (−)- and (+)-niranthin against not only HBV, but also the influenza virus (IFV). The anti-HBV activity results are summarized in Fig. 1 and ​and2,2, while the anti-IFV activity is summarized in Fig. 3 (for details, see the ESI†).Open in a separate windowFig. 1HBV-infection assay using (−)- and (+)-niranthin.Open in a separate windowFig. 2HBV-replication assay using (−)- and (+)-niranthin.Open in a separate windowFig. 3Growth-inhibition assay of IFV using (−)- and (+)-niranthin.Based on the assays using HBV-infected HepG2-hNTCP-C4 cells and HBV-replicating Hep38.7-tet cells, the amount of HBs antigen decreased in a concentration-dependent manner without apparent cytotoxicity. The 50% inhibition concentration (IC50) in the HBV-infected cells was calculated to be 14.3 ± 0.994 μM for (−)-niranthin and 9.11 ± 0.998 μM for (+)-niranthin (Fig. 1), while the IC50 in the HBV-replicating cells was calculated to be 16.2 ± 0.992 μM for (−)-niranthin and 24.2 ± 0.993 μM for (+)-niranthin (Fig. 2). These results show that (−)-niranthin and (+)-niranthin exhibit anti-HBV activity, and that there is no remarkable difference between the anti-HBV activity of both enantiomers. In contrast, based on the bioassay of (−)- and (+)-niranthins against IFV using MDCK cells, cytotoxicity of (−)-niranthin appears at >400 μM judging that cell viability without IFV is less than 80%, and (−)-niranthin inhibited IFV-infection to cells in a concentration-dependent manner on the concentration range of non-cytotoxicity, and exhibits anti-IFV activity at 200–400 μM judging that cell viability with IFV is over 50% (Fig. 3). However, (+)-niranthin does not exhibit anti-IFV activity, and similarly to (−)-niranthin, cytotoxicity appears at >400 μM. Thus, the anti-IFV activity between (−)- and (+)-niranthins is clearly different. Our findings suggest that the enantiomeric site in niranthin endows (−)-niranthin with more potent anti-IFV activity than (+)-niranthin. We speculated that the anti-HBV active site of niranthin might be a part of the molecular structure such as aromatic groups which are far from chiral centers. In contrast, anti-IFV active site of niranthin might be closer to the chiral centers (Scheme 6).Open in a separate windowScheme 6A speculation for the bioactive site of niranthin against HBV and IFV.  相似文献   

13.
Correction: Drying-induced back flow of colloidal suspensions confined in thin unidirectional drying cells     
Kai Inoue  Susumu Inasawa 《RSC advances》2022,12(27):17390
  相似文献   

14.
Bioconjugation of enzyme with silica microparticles: a promising platform for α-amylase partitioning     
Maryam Karimi  Shiva Abdolrahimi  Gholamreza Pazuki 《RSC advances》2019,9(32):18217
Here, we report the implementation of α-amylase conjugated silica microparticles for improvement of α-amylase partitioning in a PEG–organic salt-based aqueous two phase system. A direct reduction method was employed for the synthesis of silica microparticles with simultaneous introduction of α-amylase. In this context, we synthesized three different silica α-amylase conjugated microparticles with variation of tetraethyl orthosilicate concentration, and thus the effect of final particle size and enzyme loading on partitioning was also studied. The partition coefficient ratio of α-amylase to Si:α-amylase of 2.186 : 21.701 validated an almost tenfold increase in separation. The microscopic structure of the system was thoroughly investigated in order to understand the extraction mechanism and any possible denaturation. Improved partition coefficients can be interpreted by the formation of α-amylase–silica–PEG carriers. Furthermore, circular dichroism (CD) spectra validated partial unfolding of the enzyme.

Here, we report the implementation of α-amylase conjugated silica microparticles for improvement of α-amylase partitioning in a PEG–organic salt-based aqueous two phase system.

Enzymes as biomacromolecular proteins propose remarkable features for catalysis of metabolic pathways with high specificity and efficiency.1,2 New fields of application for enzymes are constantly growing. Among these, disease diagnostics, environmental monitoring, biomedical applications and immunosensing are emerging disciplines.1,3 Furthermore, recent evolution of modern biotechnology has induced rapid growth in the enzyme industry.3 On that account, high-yield isolation methods can play a crucial role in sustaining a low final cost of the product. Besides, the isolation method should not impose on the enzyme any conformational distortion and subsequent denaturation.2 In this regard, aqueous two phase systems (ATPS) propose gentle and biocompatible media for enzyme separation.4–7 The two immiscible phases are generally formed by the addition of structurally different polymers, a polymer and a salt, or two salts.4,6,8 Recently, many innovative research groups have focused on the partitioning of biomolecules in ATPS. Resultantly, polymer-based ATPS have been widely used for biomolecules’ separation and recovery.9–14Hybridization of nanoparticles with biomolecules is an innovative research area which has pioneered various biological applications such as delivery, diagnosis, separation and imaging.2,14–19 Exceptional physiochemical properties of nanoparticles make them a suitable candidate for bioconjugation. Silica has been specially incorporated in this field due to its unique intrinsic features such as high surface area to volume ratio, adjustable surface chemistry and biocompatibility. Silica’s affinity toward various biomolecules can be modified by attachment of desired functional groups such as hydrophilic, hydrophobic, acidic or basic groups to the surface.20–24A recent study reported the effect of bioconjugation of horseradish peroxidase to colloidal Au nanoparticles and subsequently the protein partitioning in ATPS was significantly improved.25 Furthermore, a recent pioneering research study described the effect of the introduction of silica nanoparticles in ATPS as an additive and significant enhancement of enzyme recovery was observed.2In this communication, we report bioconjugation of α-amylase with silica in the process of synthesis of silica microparticles with a standard Stöber method.26 In this context, we studied the effect of variation of tetraethyl orthosilicate (TEOS) concentration on the synthesized particles. Moreover, we introduced the novel enzyme–microparticle carriers in conventional polyethylene glycol (PEG)–trisodium citrate (Na3 citrate) ATPS and to a notable degree partitioning was improved. For the synthesis of conjugated silica–α-amylase microparticles, a direct reduction method according to the Stöber method was employed. In this method, hydrolysis and condensation of TEOS in ethanol with the introduction of ammonium hydroxide was performed.27 α-Amylase along with TEOS was added to the starting solution comprising ethanol, water and ammonia. After sufficient stirring, the whitish precipitate was washed, centrifuged and dried. The produced particles are labelled Si:α-amylase for future reference (Fig. 1).Open in a separate windowFig. 1Schematic illustration of conjugated silica–α-amylase microparticles.Using this scenario, we synthesized three different Si:α-amylase particles; however, characterization of these particles was required for thorough comprehension of the system. For this reason, FTIR spectroscopy was required to confirm conjugation in the synthesized Si:α-amylase particles. As can be inferred from Fig. 2b and c, the highest band at around 1100 cm−1 is due to Si–O–Si asymmetric stretching vibrations. The band at 470 cm−1 is associated with the Si–O–Si bending vibration. It can be interpreted, from the comparison of Fig. 2b and (c), that all the signature bands of silica are intact in the Si:α-amylase particles. Accordingly, no dramatic change in the silica structure is observed; however, the emergence of a new absorption band of the amide group at 1470 cm−1 (Fig. 2c) hints at the adsorption of α-amylase to the silica surface.Open in a separate windowFig. 2FTIR spectra of pure α-amylase, pure silica and α-amylase conjugated silica particles. (a) Pure α-amylase; (b) pure silica; (c) α-amylase conjugated silica particles.Dynamic light scattering (DLS) was developed as an analytical tool for prediction of the hydrodynamic size of nanoparticles. In this study, the effect of TEOS concentration on the final particle size of Si:α-amylase was investigated. Additionally, the Z-average of the synthesized particles is tabulated in 28 Thus, it is speculated that increasing the amount of TEOS in the synthesis of Si:α-amylase particles leads to an increase in the final particle size. This is mainly due to the increase in the particle size of silica prior to conjugation with α-amylase.Size distribution of α-amylase conjugated silica particles with DLS
ParticleTEOS amount (ml) Z-Average (nm)
Si:α-amylase11.55557
Si:α-amylase29.971088
Si:α-amylase314.851374
Open in a separate windowExact enzyme loading on the silica surface was estimated using TGA analysis (Fig. 3). Thus, the conjugated particles were placed in the chamber and they were exposed to temperature variation from 25 °C to 800 °C. A weight loss signature was observed in the range 60 °C to 170 °C which was assigned to the decomposition of α-amylase. Consequently, out of the total mass of the conjugated particles, 15.23, 13.9 and 13.78% was due to the α-amylase and the rest was the contribution of the silica particles. It can be inferred that the decrease in the final particle size is accompanied by the augmentation in the enzyme loading on the silica surface. This observation can be associated with the increase in the surface area, porosity and pore volume. In order to validate this assumption, Barrett–Joyner–Halenda (BJH) analysis was conducted. This method determines pore size distribution and specific pore volume.Open in a separate windowFig. 3Thermogravimetric analysis of α-amylase conjugated silica particles: () Si:α-amylase1; () Si:α-amylase2; () Si:α-amylase3.As can be observed (Fig. 4), all of the synthesized particles have type II isotherms, which is characteristic of multilayer adsorption in non-porous solids. Accordingly, the pore size distribution of the synthesized particles was in the range of 1–155 nm. Moreover, 27Open in a separate windowFig. 4The N2 adsorption–desorption isotherm of (a) Si:α-amylase1; (b) Si:α-amylase2; (c) Si:α-amylase3 particles.Surface properties of synthesized silica–α-amylase particles
Particle V p (cm3 g−1) d p,peak (nm) a p (m2 g−1)
Si:α-amylase10.070268.939.5545
Si:α-amylase20.015721.532.3298
Si:α-amylase30.012724.791.1031
Open in a separate windowIndustrial application of the enzyme requires thermal stability upon exposure to high operating temperatures. DSC analysis was performed for evaluation of the effect of temperature upon the activity and stability of α-amylase conjugated silica particles. Consequently, differences in the thermal behavior of α-amylase and Si:α-amylase particles are illustrated in Fig. 5. Comparatively, Si:α-amylase particles demonstrate less temperature variation with heat flow. This signifies that the presence of silica leads to an increase in heat capacity in Si:α-amylase. Resultantly, α-amylase manifests higher thermal stability upon conjugation.Open in a separate windowFig. 5DSC analysis of α-amylase and α-amylase conjugated silica particles: () α-amylase; () Si:α-amylase1.Variation in TEOS concentration while synthesizing α-amylase conjugated silica particles gave rise to various particle sizes. Accordingly, its subsequent effect on α-amylase partitioning in PEG1000–Na3 citrate ATPS was evaluated. Besides, the feed’s initial concentration had a noticeable effect on the partitioning behavior of the biomolecule. For this reason, the effect of the initial concentration of phase forming components (PEG1000 and Na3 citrate) along with Si:α-amylase particles on partitioning of the enzyme was investigated. On that account, a Box–Behnken design was selected for the design of experiments and the respective partition coefficients (Table S3†) were evaluated. The partition coefficient of the biomolecule is defined as:1where [α-amylase]PEG is the concentration of α-amylase in the PEG-rich phase and [α-amylase]salt is its respective concentration in the salt-rich phase.In this study, the smallest sized silica–α-amylase particle manifests the best recovery in terms of the partition coefficients. This could be interpreted from the TGA analysis which resulted in higher enzyme loading in Si:α-amylase1. For visual indication, a response contour plot for partitioning of Si-α-amylase1 is plotted in Fig. 6. The partition coefficients increase with the increase in the initial concentration of PEG1000. The increase in the initial concentration of PEG1000 makes the polymer-rich phase more hydrophobic. Consequently, it can be inferred that the extraction of the biomolecule is controlled by hydrophobic interactions. However, partition coefficients of the conjugated enzyme decrease with the increase in organic salt concentration. Increasing salt concentration causes water molecules to strongly bind to the salt. Consequently, a strong competition between the salt ions and enzyme molecules for water molecules forms, which results in a decrease in the enzyme solubility. Thus, the enzyme may segregate to the salt-rich phase.29,30 Besides, it is of great scientific importance to validate the improvement of the partition coefficients of α-amylase upon conjugation with silica microparticles. For this reason, the same experimental procedure was employed to estimate the partition coefficients of α-amylase in PEG-based ATPS (Table S2†). Consequently, the partition coefficient ratio of α-amylase to Si:α-amylase is 2.186 : 21.701 which represents a notable improvement in enzyme separation.Open in a separate windowFig. 6Response contour plots for partitioning of Si–α-amylase1 in PEG1000–Na3 citrate ATPS.We applied FE-SEM for complete comprehension of the structure of the PEG-rich top phase. The aqueous two phase system was prepared and FESEM was performed after resting overnight. In the non-extractive (presence of no biomolecule) top phase (Fig. 7a), spherical particles of PEG with average size of 300 nm were spotted. However, the addition of the enzyme as the partitioning particle induced the detection of partially agglomerated α-amylase (Fig. 7b). It has been noted that a cysteine residue (C84) on the catalytic domain of α-amylase is mainly responsible for enzyme agglomeration.31 Besides, enzyme agglomeration can be obstructed by repulsive van der Waals and electrostatic energy barriers. Thus, ligation on the cysteine residue can be observed after proper sterical orientation of the enzyme with simultaneous conquest of the energy barriers. However, colloidal enzyme agglomerates are partially obstructed by the presence of PEG as the polymer chains circumvent α-amylase. Introduction of silica–α-amylase particles in ATPS leads to the presence of different particles. Partial removal of α-amylase from the conjugated particles led to the production of unconjugated enzyme and silica particles. Naturally, we would expect the appearance of enzyme–silica–polymer carriers (Fig. 7c). At our working pH, silica is hydrated and thus attachment of the positively charged PEG to the silanol groups is facilitated. On the other hand, α-amylase also adjoins the silica surface leading to the formation of α-amylase–silica–PEG carriers. Consequently, significant amelioration of the partition coefficient is validated.Open in a separate windowFig. 7FE-SEM images: (a) PEG-rich upper phase without biomolecule, (b) α-amylase in the PEG-rich top phase, (c) silica–α-amylase particles in the top phase.Recently, circular dichroism (CD) has been widely applied for characterization of the structure of enzymes. When enzymes are exposed to polarized light they show dichroism due to the amino acids and their ordered chiral structure. The secondary structure of the α-amylase before and after the conjugation can be speculated on due to the differential absorption of polarized light. Secondary structureα-Amylase (%)Si:α-amylase (%)α-Helix1.900.3β-Sheet81.4083.90β-Turn00Random coil16.7015.80Open in a separate windowIn conclusion, we propose the synthesis of α-amylase conjugated silica microparticles for improvement of enzyme separation in PEG-based ATPS via the formation of α-amylase–silica–PEG carriers. Additionally, no denaturation was observed while partial unfolding of the enzyme was validated with CD. Furthermore, the graphical abstract demonstrates the main highlights of this research work.  相似文献   

15.
Microbubble flows in superwettable fluidic channels     
Mizuki Tenjimbayashi  Kotaro Doi  Masanobu Naito 《RSC advances》2019,9(37):21220
The control of bubble adhesion underwater is important for various applications, yet the dynamics under flow conditions are still to be unraveled. Herein, we observed the wetting dynamics of an underwater microbubble stream in superwettable channels. The flow of microbubbles was generated by integrating a microfluidic device with an electrochemical system. The microbubble motions were visualized via tracing the flow using a high-speed camera. We show that a vortex is generated in the air layer of the superaerophilic surface under laminar conditions and that the microbubbles are transported on the superaerophilic surface under turbulent conditions driven by the dynamic motion of the air film. Furthermore, microbubbles oscillated backward and forward on the superaerophobic surface under turbulent conditions. This investigation contributes to our understanding of the principles of drag reduction through wettability control and bubble flow.

Microbubble flows inside a superwettable channel revealed underwater superwetting phenomena under flow conditions, contributing to the understanding of real-world environmental wetting systems.

Nature offers us ideas for the design of materials with superwettability.1 In superwettable systems, the wetting of air underwater has generated interest recently.2–6 For example, penguin feathers are superaerophilic, with an air layer forming on the surface underwater, which allows penguins to swim in the sea with small amounts of drag.2,3 Inspired by this, researchers have theoretically and/or experimentally studied the influence of wettability on drag reduction underwater.4–6 In addition, fish scales are superaerophobic, which offers the idea of designing no-bubble adhesion electrodes that demonstrate high and stable oxygen evolution reaction performance.7,8 However, despite the development of superwettable materials for the controllable adhesion of air and/or bubbles underwater,9 the wetting dynamics of bubbles under flow conditions, which we must consider in real environments, have not been investigated.Herein, we generated microbubble flows parallel to superwettable substrates inside a microfluidic device10,11 and studied the wetting dynamics through integrating an electrochemical setup12 with a microfluidic device, as shown in Fig. 1. The bubbles were formed through the electrolysis of water (see the ESI†). Two platinum plates were used: one as the working electrode and the other as the counter electrode. To increase the electrical conductivity, 2.0 mM K2SO4 was added to the water. The bath water–vapor interfacial tension, γLV, was 71.9 ± 3.6 mN m−1 (n = 15) and the pH of the water was 7.8. We applied a current of ∼0.25 mA cm−2 to generate microbubbles with a diameter of 463.9 ± 245.1 μm (n = 120). The microfluidic device was generated using a 3D printer and connected to a water-flow generator (see the ESI† for the dimensions of the device). The microbubbles generated around the electrodes moved in the direction of the water flow and the coated substrates were placed parallel to the flow.Open in a separate windowFig. 1A schematic illustration of the microfluidic device with an electrochemical setup. We generated a flow of microbubbles and investigated the influences of coating wettability and flow type on the microbubbles dynamics via high speed camera observations. Scale bar: 10 mm.We used the microbubbles as tracers and analyzed their flow as well as that of the water (i.e. microbubble image velocimetry), as shown in Fig. 2. We controlled the Reynolds number, Re = 4Q(πDν)−1 (Q is the flow rate of the water, D is the tube diameter, and ν is the kinetic viscosity of the water). Laminar flow was obtained at Re = 79.21 and turbulent flow was obtained at Re = 396.06 (Fig. 2A). Under laminar flow conditions, the flow speed was nearly constant and the flow direction was close to perpendicular to the substrate (φ ≈ 0, where φ is the angle between the microbubble direction of movement and the width direction of the substrate) in all areas; this behavior was time-independent (Fig. 2B and C). Under turbulent flow conditions, the flow speed was not constant, and the flow direction was unstable (φ fluctuated between −180 and 180°) in all areas. We confirmed that the separation of flow did not occur, at least during the observation period, since the flow direction was parallel to the superwetting microfluidic device.Open in a separate windowFig. 2The flow conditions of the microbubbles. We created laminar and turbulent flows through altering the Reynolds number. (A) Flow velocimetry of the microbubbles under laminar (left) and turbulent (right) flow conditions; scale bar: 10 mm. (B) Velocity and flow direction profiles of microbubbles over the flow area under laminar (left) and turbulent (right) flow conditions. (C) Average velocity and flow direction fluctuations with time under laminar (left) and turbulent (right) flow conditions.We then prepared substrate coatings with superaerophilicity and superaerophobicity. Superaerophilic substrates were fabricated according to our previous study.12 Concisely, a glass plate was dip-coated with a mixture of zinc oxide micro-tetrapod powder for surface roughening and polydimethylsiloxane for aerophilization. Superaerophobic surfaces were prepared through modifying a glass substrate with hydroxy groups using an aqueous potassium hydroxide solution.13 The wettability of the superaerophobic surfaces in relation to bubbles was confirmed via measuring the underwater bubble contact angle (θ); the results are shown in Fig. 3. We calculated the adhesion forces of bubbles, Fadh = πl2γLV(1 + cos θ)/4,14 where l is the bubble–solid adhesion length. On the superaerophilic surface, the adhesion force was 3.2 × 103 μN, and on the superaerophobic surface the force was 4.37 μN for 6 μL bubbles.Open in a separate windowFig. 3Wettability of the coatings. (A) schematic illustration of the measurement of the underwater air contact angle. The contact behavior of 6 μL microbubbles underwater on superaerophilic (B) and superaerophobic (C) surfaces.In Fig. 4, we observed air film formation on superaerophilic surfaces under laminar and turbulent flow conditions. As we have previously shown, when microbubbles are vertically deposited on superaerophilic surfaces, a uniform air layer is formed.10 In the present study, under both laminar and turbulent flow conditions, a uniform air layer formed on the superaerophilic surfaces, but the air layers grew non-uniformly with the deposition of microbubbles owing to Rayleigh–Taylor instability14 (Fig. 4A and B). In all five independent observations, the shape of the air layer was non-uniform; thus, the flow of microbubbles influenced the shape of the air layer. However, bubbles with l = 4–7 mm formed on the surfaces under both laminar and turbulent flow conditions.Open in a separate windowFig. 4Microbubble deposition behavior on a superaerophilic surface under laminar (A) and turbulent (B) flow conditions. The top and bottom parts of the images are the initial and time-aged stages, respectively. (C) The vortex motion of microbubbles on deposited air films under laminar flow conditions. (D) Microbubbles transported on a superaerophilic surface under turbulent conditions driven by the dynamic motion of the air film. (E) and (F) Schematic representations of the microbubble behavior from (C) and (D), respectively. All scale bars: 10 mm.After aging for 1000 s, a continuous air film formed on the superaerophilic surfaces under turbulent conditions. However, the shape was unstable and changed with time (Fig. 4D). In Fig. 4C and E, we observe the formation of a vortex on the hemispherical air film under laminar flow conditions (see Movie S1†). This phenomenon is interesting because under laminar flow conditions a vortex should not be generated (Fig. 2A); this cannot be explained using Bernoulli''s theorem15 and the generation of a vortex suggests the separation of flows, which works to decrease flow resistance at the interface. Vortex generation may be due to the coalescence of microbubbles with the air layer, causing a change in the curvature of the hemispherical air film. This, in turn, would result in a change in the Laplace pressure of 2ΔκγLV, where Δκ is the change in curvature. There is a fluctuation in the vertical force torque to generate the vortex, and the force should be balanced by a Kutta–Joukowski force in the form of 2γLV dκ/dt ≈ ρΓU, where ρ is the density of flows, Γ is the vortex constant, and U is the velocity of the constant laminar flow.16In Fig. 4D and F, we observe that microbubbles on the air film were transported as the shape of the air film dynamically changed to a wave-like nature; however, the microbubbles and air film did not coalesce (see Movie S2†). This indicates that a thin water layer exists between the microbubbles and the air film to prevent coalescence, whereas microbubbles are trapped on the air film by the buoyancy force of the microbubbles, which ≈(Δρ)Ωg, where Δρ is the difference in densities between a bubble and water, Ω is the volume of a microbubble, and g is gravitational acceleration.We then observed the dynamics of the microbubbles on the superaerophobic surfaces (Fig. 5). As we have previously shown, when microbubbles are vertically deposited on superaerophobic surfaces, they are uniformly deposited on the surface and have a spherical shape.12 Under both laminar and turbulent flow conditions, microbubbles were deposited on the superaerophobic surfaces with spherical shapes but with non-uniform deposition (Fig. 5A and B). We then observed the motion of bubbles in contact with the superaerophobic surfaces. Under laminar flow conditions, microbubbles adhering to the surface moved in the direction of the flow (Fig. 5C and Movie S3†). In contrast, turbulent flow conditions caused the microbubbles to oscillate backward and forward (Fig. 5D and Movie S4†). The velocimetry profiles in Fig. 5E and F confirm that the bubble motion is linear in time under laminar flow, but it varies under turbulent flow (with the velocity periodically becoming negative). Despite the periodic negative velocity under turbulent flow conditions, the bubbles go forwards in the flow direction, which is not due to the laminar boundary but because the turbulent flow has more positive components than negative ones. This is because the length of positive motion under turbulent flow conditions increases with the size of the bubbles, obeying Newton''s viscosity law.17 Thus, we confirmed that the motion of bubbles on superaerophobic surfaces is influenced by the flow conditions. The bubble motion distance on superaerophobic surfaces increased with bubble diameter.Open in a separate windowFig. 5Microbubble deposition behavior on a superaerophobic surface under laminar (A) and turbulent conditions (B). The top and bottom parts of the images are the initial and time-aged stages, respectively. (C) Linear motion of the microbubbles on the surface under laminar flow. (D) The oscillating motion of microbubbles on the surface under turbulent flow. (E) Motion distance and (F) velocity analysis of microbubbles under laminar (left) and turbulent (right) conditions for different bubble diameters (2R). All scale bars: 10 mm.  相似文献   

16.
Insight into trifluoromethylation – experimental electron density for Togni reagent I     
R. Wang  I. Kalf  U. Englert 《RSC advances》2018,8(60):34287
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–Caryl 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 refinement33,34 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 oxygen37,38 or iodine and nitrogen.39–41Fig. 1 and ​and22 show that the Caryl–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 Caryl–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 MoleCoolQt44,45). 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.  相似文献   

17.
Ratchet-like mechanism in a long-life photoproduct of salicylideneaniline enclathrated in a pillared-layer guanidinium disulfonate structure     
Kentaro Nakayama  Taisuke Manako  Ryo Koibuchi  Isao Yoshikawa  Hirohiko Houjou 《RSC advances》2021,11(23):13739
Salicylideneaniline (SA) was found to exhibit extraordinary long-life photochromism upon being included in a cavity of guanidinium organosulfonate and exhibited a lifetime of ∼30 times that of a pure SA crystal. Crystal structure analysis suggested that the sulfonate molecule in the apo-host provided a flexible cavity space that kinetically trapped SA in its photo-isomerized form, as if it was locked by a ratchet-like mechanism.

A certain molecular environment in a hydrogen-bonded framework may extremely prolong the lifetime of photo-induced, colored species.

Crystal engineering is a promising strategy for the modification of the chemical and physical properties of molecular solids to obtain desirable functions.1 For example, salicylideneanilines (SAs), which are known to exhibit either photochromism or thermochromism depending on their molecular environment,2–4 are often employed to exemplify the effects of polymorphs, cocrystallization, salification, or inclusion in a porous coordination network.5–8 The chromism of SA originates in the interconversion of three tautomers: the enol, cis-keto, and trans-keto forms (Chart 1).9,10 Therefore, the modification of the energy landscape by changing the surroundings of the SA chromophore facilitates chromism. Guanidinium organosulfonate (GS), which is known to spontaneously form a pillared-layer structure,11–14 is a promising candidate for providing a variety of molecular hosts to accommodate SA molecules as guests. In the present study, the use of biphenyl-4,4′-disulfonate as a pillar resulted in the clathrate compound, SA@1, which was a photochromic compound with an extraordinarily long life, whereas the use of naphthalene-2,6-disulfonate afforded a photo-inactive clathrate compound, SA@2.Open in a separate windowChart 1Three tautomers of salicylideneaniline relevant to its chromic behaviour.Molecular apo-hosts 1 and 2 were prepared in accordance with studies presented by Ward et al.14,15 After their preparation, 1 and 2, were dissolved in methanol with 3 equivalents (to guanidinium) of SA, respectively, and were left to sit until the open evaporation initiated crystallization.† The products were examined by single-crystal X-ray structural analysis, which revealed that 1 and 2 afforded the molecular clathrates SA@1 and SA@2, respectively. Several crystal structures have been reported for several clathrates and solvates of 1 and 2,14 and their connection topology that features hydrogen-bonding networks is known to vary with the type of guest and solvent molecules. Chart 2 illustrates the framework of the putative apo-hosts 1 and 2 in SA@1 and SA@2. The ratio of SA : disulfonate was 1 : 2, which implied that each unit cell (with volumes of 1227.95 Å3 for SA@1 and 1098.28 Å3 for SA@2) contained one molecule of SA (Fig. 1). However, the NMR profiles revealed that the ratio (0.44 and 0.41) of SA to sulfonate molecules was lower than that (0.50) derived from stoichiometry (Fig. S1†), implying that the bulk product contained an appreciable amount of the apo-hosts. FTIR spectra16 (Fig. S2†) and powder XRD patterns (Fig. S3†) also implies the contamination of the apo-host.Open in a separate windowChart 2Schematic representation of apo-hosts 1 and 2. The connection topology featuring hydrogen-bonding networks can be observed in their SA-clathrates, SA@1 and SA@2.Open in a separate windowFig. 1Crystal structures of (a) SA@1 and (b) SA@2. Views along other directions are available in Fig. S4.†Upon irradiation with UV light, the color of the SA@1 crystal changes from pale yellow to orange, whereas that of the SA@2 crystal does not. Absorption spectra were subsequently obtained with a microscope-based UV-vis absorption spectrometer equipped with a temperature controller and a high-pressure Hg lamp (through a 330–380 nm band path filter) to investigate this.17–19 Upon irradiation with the Hg lamp at 15 °C, the SA@1 sample immediately shows an intense absorption band at ∼500 nm with a blunt vibronic structure (Fig. 2a). An unmixed SA molecule is known to exhibit three crystalline polymorphs, i.e. α1-, α2-, and β-forms,20 among which the α1-form is the most common photochromic species. The absorption spectrum of SA@1 in the photo-stationary state is quite similar to those of α1-SA,5 suggesting that the newly appeared band can be attributed to the photo-induced trans-keto form. When the sample is cooled to −60 °C, the spectrum in the photo-stationary state reveal a clearer structure, whereas that in the dark-adapted state is almost unchanged. The spectra of SA@2 without the Hg lamp are noted to be similar to those of SA@1; however, they did not show significant changes upon UV irradiation (Fig. 2b). Both samples were photoluminescent but with different spectral profiles: SA@1 exhibited an orange emission peak at ∼590 nm, and SA@2 exhibited a yellowish-green emission peak at ∼520 nm (Fig. 3). This difference is similar to the behavior observed in the photochromic and thermochromic polymorphs of 3,5-di-tert-butylsalicylideneaniline.17 There are two possible reasons for the spectral shift: (1) the alteration of electronic state in SA molecule due to conformational change and/or intermolecular interactions inside the cavity; (2) reabsorption of a 500–600 nm region of the emission by the photo-product. The first reason is rather unlikely in view of a more planar structure (angle between two phenyl rings is 2.8°) of SA@2 than that (23°) of SA@1. Interestingly, the luminescence spectra of SA@1 appeared similar to those of SA@2 after the SA@1 crystals were pulverized in an agate mortar; however, its photochromism was maintained. This phenomenon implies that the pulverization induced a partial collapse of the pillared-layer structure, but leaves some room for discussion about the coexistence of yellowish-green luminescence and photochromism that seems contradictory to the second reason above. These observations will be a clue to a complete understanding of the current system, and worth further inspecting in the future.Open in a separate windowFig. 2Single-crystal UV-vis absorption spectra obtained with and without UV irradiation in (a) SA@1 and (b) SA@2. (inset) Microscope images at 25 °C.Open in a separate windowFig. 3Emission spectrum of SA@1, SA@2, as compared with that of β-SA. Spectra of SA@1 after grinding with a mortar is overlaid.The duration of photo-coloration for SA@1 was notably longer than that for α1-SA. This was investigated via an examination of the bleaching process by measuring the absorbance decay curves at 480 nm, starting from the photo-stationary state at 15 °C (Fig. 4). As previously noted,18,19 the decay curves do not fit well to a single exponential function; hence, a time constant cannot be extracted. Instead, the values of T50 and T95 (durations at 50% and 95% decay, respectively) were compared, which revealed that the lifetime of SA@1 was 30 times longer than that of α1-SA (21 and Ohashi et al.,22 respectively: these values were measured in the dark); the results suggest that SA@1 possesses a longer lifetime (∼2×) than that of SA-NO2 (Fig. 4).Open in a separate windowFig. 4Comparison of relaxation times in the photo bleaching of SA@1, SA-NO2, and α1-SA.Comparison of the lifetimes (s) of SA@1, α1-SA, and SA-NO2
Compound T 50 T 95
SA@1329910
α1-SA1131
SA-NO2223361
Open in a separate windowThe crystal structure of SA@1 was solved under the P1̄ space group, which means that the SA molecule was assumed to have a disorder ratio of 1 : 1 for opposite orientations, with respect to the pseudo-inversion point at the center of the C Created by potrace 1.16, written by Peter Selinger 2001-2019 N bond. In addition, the phenyl rings of biphenyl-4,4′-disulfonate were assumed to have disorders for rotations of 17–40° with respect to the axis along S⋯S (Fig. 5). These observations suggest that the cavity inside 1 can be flexibly shaped in accordance with the structure of the guest molecule(s). For reference, the crystal structure of the o-dichlorobenzene clathrate of 1 (CCDC refcode XAQWUH),23 which has a unit cell and packing structure similar to those of SA@1, was solved without assuming any disorders, and revealed an almost parallel arrangement of the biphenyl moieties in a planar conformation. It is worth mentioning that this arrangement overlays decently with one of the disordered structures (shown in blue and magenta in Fig. 5) in SA@1 (Fig. S5†).Open in a separate windowFig. 5Crystal structure of the biphenyl moieties surrounding the SA molecule in SA@1 (view along 101 direction). The structures are shown using an overlay of two different conformations, in blue and orange, and in magenta and pale green.The torsion angle (θ) between the two phenyl rings in the SA molecule has been noted to indicate the possibility of photochromism. Previous studies have suggested that SA becomes thermochromic if the molecule is nearly planar (θ < ∼30°), whereas it appears photochromic if the molecule is twisted (θ > ∼30°).2–4 However, SA@1 (θ = 23°) narrowly fails at being categorized as a photochromic crystal in accordance with this criterion, whereas SA@2 (θ = 2.8°) is appropriately predicted as non-photochromic. Another requisite for photochromism involves a loosely packed (open) structure that allows cis-to-trans photoisomerization.1–3 However, there is a lack of definitive discussions on the quantitative relationship between the degree of the open structure and photochromic activity. In addition to the difficulty in quantifying the open structure, the conventional dualistic classification into photochromic and thermochromic (non-photochromic) crystals is also an issue; it is possible for a photochromic crystal with an extremely loose packing to have a very high bleaching speed, and get classified as non-photochromic. Therefore, a sufficient long life of the photoproduct can be another requisite for photochromism. For SA-NO2 and polymorphs of its carboxylate analogue, a positive correlation between the lifetime and stability of the trans-keto form has been inferred.22Combining the above analyses, an explanation for the long-life photochromism of SA@1 can be proposed. The putative apo-host 1 possesses a cavity volume that is sufficient to accommodate the SA molecule, and the cavity shape is flexibly adjusted by the rotation of the phenyl rings of the pillars. When photo-isomerization occurs, the phenyl rings can rotate to follow the structural change. The rings rotate almost freely; however, they do not rotate independently because of the inter-pillar distance of 6.2 Å, which is insufficient for the two phenyl rings to avoid van der Waals contacts. Therefore, the biphenyl moieties serve as meshing gears to prevent the photoproduct from relaxing to the thermodynamically stable enol form; this mechanism can be compared to that of a ratchet gear. By contrast, SA@2, in which the cavity (480 Å3) is slightly smaller than that (546 Å3) of SA@1,24 neither has enough volume to accommodate the twisting of the SA molecule, nor the flexibility to follow the structural change upon isomerization.In summary, drastic changes in the photochemical properties of SAs were observed via the formation of clathrates of GS compounds. Since the discovery of GS compounds by Etter and Ward,11–13 their pillared-layer structures have been extensively applied for the isolation and stabilization of guest molecules.25 The inclusion of functional dyes such as azobenzene,14 coumarin,15 and ROY26 into GS hosts has been accomplished. It is worth noting that the torsion angle of ROY can be adjusted by changing the type of bifunctional organosulfonic acid employed. The present study demonstrates the possibility of GS clathrates to facilitate new systems with which the various properties of photochromic compounds can be examined in a controlled molecular environment.  相似文献   

18.
On-surface synthesis of π-conjugated ladder-type polymers comprising nonbenzenoid moieties     
Jos I. Urgel  Julian Bock  Marco Di Giovannantonio  Pascal Ruffieux  Carlo A. Pignedoli  Milan Kivala  Roman Fasel 《RSC advances》2021,11(38):23437
On-surface synthesis provides a powerful approach toward the atomically precise fabrication of π-conjugated ladder polymers (CLPs). We report herein the surface-assisted synthesis of nonbenzenoid CLPs from cyclopenta-annulated anthracene monomers on Au(111) under ultrahigh vacuum conditions. Successive thermal annealing steps reveal the dehalogenative homocoupling to yield an intermediate 1D polymer and the subsequent cyclodehydrogenation to form the fully conjugated ladder polymer. Notably, neighbouring monomers may fuse in two different ways, resulting in six- and five-membered rings, respectively. The structure and electronic properties of the reaction products have been investigated via low-temperature scanning tunneling microscopy and spectroscopy, complemented by density-functional theory calculations. Our results provide perspectives for the on-surface synthesis of nonbenzenoid CLPs with the potential to be used for organic electronic devices.

On-surface synthesis provides a powerful approach toward the fabrication of π-conjugated ladder polymers (CLPs). The synthesis of nonbenzenoid CLPs is achieved following two activation steps, including the formation of an intermediate 1D polymer.

Conjugated ladder polymers (CLPs) represent an attractive type of π-conjugated polymers which consist of a sequence of fused rings with adjacent rings sharing two or more atoms.1 The restriction of bond rotations inherent to CLPs represent an important approach that has been systematically pursued since the 1990s.2,3 Such rigidification generally provides enhanced intermolecular π–π stacking interactions and high thermal stability, which may lead to application-relevant properties (or improved materials properties),4–10 with prospects in organic field-effect transistors,11 organic light emitting diodes,12 gas separation13,14 or optically pumped lasers.15 While the majority of CLPs reported to date have been obtained through solution chemistry,16,17 the potential of on-surface synthesis to overcome some of the intrinsic challenges of solution-based approaches, including low solubility, high reactivity of reaction products or precursors and limited diversity of reaction designs, toward the effective fabrication of tailored ladder polymers18–20 has increasingly come to forth in the last decade only.21In this context, graphene nanoribbons (GNRs)22 represent the most acknowledged class of CLPs. Despite the recent expansion of the GNR catalogue, the controlled incorporation of nonbenzenoid rings into the GNR backbone to modulate the structural23,24 and electronic25,26 properties remains comparably scarce. Theoretical calculations have anticipated the existence of several nonbenzenoid carbon allotropes which are expected to exhibit pronouncedly different (opto)-electronic properties,27,28 mechanical stability,29,30 or electron transport properties.31 Only recently, the on-surface synthesis of several CLPs containing nonbenzenoid rings has been reported.32–38 Nevertheless, systematic investigations of the structural and electronic properties resulting from selective incorporation of nonbenzenoid rings into CLPs are still lacking.In this work, we introduce an exemplary approach toward the on-surface formation of nonbenzenoid π-conjugated ladder-type polymers on a coinage metal surface under ultrahigh vacuum (UHV) conditions. To this end, we synthesized in solution 2,7-dibromocyclopenta[hi]aceanthrylene as a precursor (1),39 which features electron acceptor properties due to the presence of the 5-membered rings.39,40 Compound 1 can be sublimed intactly and converted to nonbenzenoid CLPs (3) by thermal activation on the metal surface (see ESI† for the precursor synthesis and characterization). The reaction route toward the formation of the CLP 3, illustrated in Scheme 1, follows two surface-assisted steps including dehalogenative homocoupling to yield an intermediate one-dimensional (1D) polymer (2) and cyclodehydrogenation to form 3. Interestingly, two different carbon–carbon (C–C) bonds between adjacent monomers can be formed in the cyclodehydrogenation step, resulting in six- or five-membered ring formation between monomers (3a and 3b, respectively). All the synthesis steps are investigated by scanning tunneling microscopy (STM) and complemented by density-functional theory (DFT).Open in a separate windowScheme 1On-surface synthesis of nonbenzenoid CLPs 3a and 3b.The chemical structure of 2 and 3 are unambiguously identified by ultrahigh-resolution STM (UHR-STM) and their electronic properties studied by scanning tunneling spectroscopy (STS).To study the on-surface reactions illustrated in Scheme 1, we sublimed precursor 1 onto an atomically clean Au(111) surface held at room temperature and subsequently annealed at 330 °C. High-resolution STM images (Fig. 1a and b) reveal the predominant presence of 1D polymers together with rounded protrusions between the chains, which we assign to bromine atoms detached from 1. To confirm the chemical structure of 2, ultrahigh-resolution STM (UHR-STM) images acquired with a CO-functionalized tip recorded in the Pauli repulsion regime41,42 were performed (Fig. 1c). Hereby, intramolecular features corresponding to the cyclopenta[hi]aceanthrylene molecular backbone linked via C–C bonds through the pentagons of each molecular subunit are distinguished (see Fig. S1† for a detailed STS and voltage dependent differential conductance spectra characterization of a segment of 2). Additionally, UHR-STM images allow us to discern single (s)-trans and -cis isomers within the same polymer chain (see Scheme S1† for the reaction pathway between adjacent s-trans and s-cis isomers). The DFT-optimized equilibrium geometry of 2 shown in Fig. 1d indicates that the polymer adopts a planar configuration, with an adsorption height of 3.3 Å with respect to the underlying gold surface.Open in a separate windowFig. 1On-surface synthesis of the 1D polymer (2) on Au(111). (a) Overview STM topography image of the surface after deposition of 1 and subsequent annealing at 330 °C, showing the predominant presence of 1D chains. Vb = −0.50 V, It = 60 pA, scale bar: 10 nm. (b) High-resolution STM image of (a) where 1D chains together with rounded protrusions, assigned to bromine atoms, are observed. Vb = −0.20 V, It = 70 pA, scale bar: 2 nm. (c) CO-functionalized UHR-STM image of 2 where the intramolecular features of the nonbenzenoid molecular backbone in the polymers are discerned. S-cis and s-trans denote the two isomers found within a chain. Vb = 5 mV, It = 70 pA, scale bar: 2 nm. (d) Top view of the DFT equilibrium geometry of 2 on Au(111).Annealing the sample at 400 °C induced minor variations in the molecular structure of 2 and only small segments of the 1D polymer (∼8%), attributed to the onset of the cyclodehydrogenation reaction, present a different appearance (see Fig. S2† for STM and UHR-STM images). Only after a further annealing step at 420 °C, the formation of the targeted CLP 3, coexisting with a few laterally fused segments, is achieved (Fig. 2a). A zoom-in STM image (Fig. 2b), allows us to discern two different C–C coupling motifs in the formation of 3. Herein, the kinked/linear segments observed in Fig. 2b are attributed to the formation of a hexagon/pentagon (3a/3b) between two molecular units (Fig. 2c and d). Importantly, statistics over the coupling motifs observed for more than 500 molecular units indicates that the coupling through the six-membered ring is favoured over the five-membered one (3a = 58%, 3b = 32%, non-cyclodehydrogenated = 10%). This can be rationalized on the basis of simple energetic considerations. On the one hand, gas phase calculations for 3a and 3b reveal that 3a is ≈1 eV more energetically favoured compared to 3b. This energy difference is further enhanced on the substrate and 3a (Fig. 2f) is ≈1.7 eV more stable compared to 3b on Au(111). Configurations of the polymer units that would lead to the formation of 3b motifs are hindered by the fact that the polymer should undergo a torsion (deviating from linearity) that is unlikely to occur for long strands. Therefore, cyclodehydrogenation between adjacent s-trans/s-cis and s-cis/s-trans isomers (synthetic pathway (a) in Scheme S1†) implies the formation of a new hexagon (3a), while cyclodehydrogenation between adjacent s-trans/s-trans and s-cis/s-cis isomers (synthetic pathway (b) in Scheme 1) affords the formation of a new pentagon (3b, with 3bI, 3bII ≈ 50%). In addition, it is expected that the reaction mechanisms in the formation of 3a and 3b involve a rotation of cyclopenta[hi]aceanthrylene molecular units on the surface substrate, at temperatures typical for the annealing, prior to cyclization (see synthetic pathway (a) in Scheme 1 and synthetic pathway (b) in Scheme S1†).32,43,44 Finally, Fig. 2e and f display the DFT equilibrium geometry of the formed pentagon (in green in Fig. 2e) and hexagon (in blue in Fig. 2f), respectively. Both adopt a planar configuration, with an adsorption height of 3.2 Å with respect to the underlying surface.Open in a separate windowFig. 2On-surface synthesis of 3 on Au(111). (a) Overview STM topography image of the surface after annealing 2 at 420 °C, showing the formation of fully conjugated nonbenzenoid CLPs. Vb = −0.10 V, It = 100 pA, scale bar: 5 nm. (b) High-resolution STM image of 3 where kinked and linear segments can be distinguished. Vb = 0.02 V, It = 100 pA, scale bar: 1 nm. (c and d) CO-functionalized UHR-STM image and corresponding chemical sketch of the segment of 3 shown in (b) where the intramolecular features, attributed to the formation of a six-membered (3a) and a five-membered (3b) ring, respectively, are discerned. Vb = 5 mV, It = 100 pA, scale bar: 1 nm. (e and f) Top views of the DFT equilibrium geometry of 3b and 3a respectively, on Au(111). Bonds and atoms highlighted in green and blue colours show the pentagon and hexagon formed due to the cyclodehydrogenation reaction.Next, we performed STS measurements on a 3a segment (six consecutive units), whose formation is favoured over 3b, to probe its electronic structure. Voltage-dependent differential conductance spectra (dI/dV vs. V) feature characteristic peaks at −1.12 eV and +0.65 eV (Fig. 3a), which are assigned to the valence band minimum (VBM) and the conduction band maximum (CBM), respectively, corresponding to an electronic bandgap of 1.77 eV on Au(111), matching very well with the calculated band structure for an infinite 3a segment (Fig. 3b). Constant-current maps of the dI/dV signal of a 3a acquired with a CO-functionalized tip at the VBM (top) and CBM (bottom) energetic positions are shown in Fig. 3c (see Fig. S3 and S4† for comparison with the constant-height dI/dV maps of 3a as well as dI/dV vs. V and constant-current dI/dV maps of the minority 3b segment, respectively). Finally, the experimental dI/dV maps are well reproduced by the DFT-calculated local density of states (LDOS) maps for the CBM and VBM (Fig. 3d), calculated at 3 Å above the molecular plane.Open in a separate windowFig. 3Electronic properties of 3a on Au(111). (a) dI/dV spectrum of 3a, acquired at the position indicated by the blue cross (blue line), revealing a band gap of 1.77 eV, and reference spectrum taken on the bare Au(111) surface (pink line). (b) DFT calculated band structure of an infinite CLP 3a in gas phase. (c and d) Constant-current differential conductance (dI/dV) maps (c) and corresponding DFT-calculated LDOS maps (d) at the energetic positions corresponding to the VB (top) and the CB (bottom) of 3a, respectively. Tunneling parameters for the dI/dV maps: VB (Vb = −1.10 V, It = 300 pA); CB (Vb = 0.70 V, It = 300 pA). All scale bars: 0.5 nm.In conclusion, we have demonstrated a novel synthetic pathway toward the on-surface fabrication of nonbenzenoid π-conjugated ladder-type polymers on Au(111) by a combination of high-resolution STM and STS complemented with DFT calculations. A first annealing step at 330 °C induces debromination, leading to the formation of 1D polymers (2). A subsequent annealing step at 420 °C promotes the cyclodehydrogenation and the consequent formation of nonbenzenoid CLPs (3). Interestingly, two types of C–C coupling motifs, comprising the formation of a hexagon (3a) or a pentagon (3b) between cyclopenta[hi]aceanthrylene subunits, are observed. Such C–C couplings arises from the presence of s-trans and s-cis isomers at the polymer step, though the formation of a hexagon, which implies cyclodehydrogenation between adjacent s-trans/s-cis and s-cis/s-trans isomers, is favoured over the formation of the pentagon (cyclodehydrogenation between adjacent s-trans/s-trans and s-cis/s-cis isomers). We expect that the synthetic strategy presented in this work is of general relevance for the synthesis of novel conjugated ladder-type polymers, and will contribute to expand the knowledge in this field with notable potential for device applications.  相似文献   

19.
Thiophene-containing tetraphenylethene derivatives with different aggregation-induced emission (AIE) and mechanofluorochromic characteristics     
Ya Yin  Zhao Chen  Yue Yang  Gang Liu  Congbin Fan  Shouzhi Pu 《RSC advances》2019,9(42):24338
Four thiophene-containing tetraphenylethene derivatives were successfully synthesized and characterized. All these highly fluorescent compounds showed typical aggregation-induced emission (AIE) characteristics and emitted different fluorescence colors including blue-green, green, yellow and orange in the aggregation state. In addition, these luminogens also exhibited various mechanofluorochromic phenomena.

Four thiophene-containing AIE-active TPE derivatives were synthesized. Furthermore, these luminogens exhibited various mechanofluorochromic phenomena.

High-efficiency organic fluorescent materials have attracted widespread attention due to their potential applications in organic light-emitting devices and fluorescent switches.1–8 Meanwhile, smart materials sensitive to environmental stimuli have also aroused substantial interest. Mechanochromic luminescent materials exhibiting color changes under the action of mechanical force (such as rubbing or grinding) are one important type of stimuli-responsive smart materials, which can be used as pressure sensors and rewritable media.9–18 Bright solid-state emission and high contrast before and after grinding are very significant for the high efficient application of mechanochromic fluorescence materials.19–28 However, a majority of traditional emissive materials usually exhibit poor emission efficiency in the solid state due to the notorious phenomenon of aggregation caused quenching (ACQ), and the best way to solve the problem is to develop a class of novel luminescent materials oppositing to the luminophoric materials with ACQ effect. Fortunately, an unusual aggregation-induced emission (AIE) phenomenon was discovered by Tang et al. in 2001.29 Indeed, the light emission of an AIE-active compound can be enhanced by aggregate formation.30–32 Obviously, it is possible that AIE-active mechanochromic fluorescent compounds can be applied to the preparation of high-efficiency mechanofluorochromic materials. Numerous luminescent materials exhibiting mechanochromic fluorescent behavior have been discovered up to now.33 Whereas, examples of fluorescent molecules simultaneously possessing AIE and mechanofluorochromic behaviors are still limited, and the exploitation of more AIE-active mechanofluorochromic luminogens is necessary. Organic solid emitters with twisted molecular conformation can effectively prevent the formation of ACQ effect, thus exhibiting strong solid-state luminescence. Tetraphenylethene is a highly twisted fluorophore. Meanwhile, it is also a typical AIE unit, which can be used to construct high emissive stimuli-responsive functional materials.34–37The design and synthesis of novel organic emitters with tunable emission color has become a promising research topic at present. Only a limited number of organic fluorescent materials with full-color emission have been reported to date.38,39 For example, in 2018, Tang et al. reported six tetraphenylpyrazine-based compounds. Interestingly, in film states, these luminogens exhibited different fluorescence colors covering the entire visible range, and this is the first example of realizing full-color emission based on the tetraphenylpyrazine unit.40 It is still an urgent challenge to develop novel organic luminophors with tunable emission color basing on the same core structure.In this study, four organic fluorophores containing tetraphenylethene unit were successfully synthesized (Scheme 1). Introducing the thiophene and carbonyl units into the molecules possibly promoted the formation of weak intermolecular interactions such as C–H⋯S or C–H⋯O interaction, which was advantageous to the exploitation of interesting stimuli-responsive fluorescent materials. Indeed, all these compounds showed obvious AIE characteristics. Furthermore, these luminogens emitted a series of different fluorescent colors involving blue-green, green, yellow and orange in the aggregation state. In addition, these luminogens also exhibited reversible mechanofluorochromic phenomena involving different fluorescent color changes.Open in a separate windowScheme 1The molecular structures of compounds 1–4.To investigate the aggregation-induced properties of compounds 1–4, the UV-vis absorption spectra of 1, 2, 3 and 4 (20 μM) in DMF–H2O mixtures of varying proportions were studied initially (Fig. S1†). Obviously, level-off tails were obviously observed in the long-wavelength region as the water content increased. This interesting phenomenon is generally associated with the formation of nano-aggregates.41 Next, the photoluminescence (PL) spectra of 1–4 in DMF–H2O mixtures with various water fraction (fw) values were explored. As shown in Fig. 1, almost no PL signals were noticed when a diluted DMF solution of luminogen 1 was excited at 365 nm, and thus almost no fluorescence could be observed upon UV illumination at 365 nm, and the corresponding absolute fluorescence quantum yield (Φ) was as low as 0.04%. However, when the water content was increased to 50%, a new blue-green emission band with a λmax at 501 nm was observed, and a faint blue-green fluorescence was noticed under 365 nm UV light. As the water content was further increased to 90%, a strong blue-green emission (Φ = 30.81%) could be observed. Furthermore, as shown in Fig. S2,† the nano-aggregates (fw = 90%) obtained were confirmed by dynamic light scattering (DLS). Therefore, the compound 1 with bright blue-green emission caused by aggregate formation showed typical AIE feature.Open in a separate windowFig. 1(a) Fluorescence spectra of the dilute solutions of compound 1 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different water contents (0–90%). Excitation wavelength = 365 nm. (b) Fluorescence images of 1 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different fw values under 365 nm UV light.Similarly, as can be seen in Fig. 2–4, compounds 2–4 also showed obvious aggregation-induced green emission, aggregation-induced yellow emission, and aggregation-induced orange emission, respectively. When the water content was zero, the quantum yields of compounds 2–4 were 0.04%, 0.05% and 0.46%, respectively, while as the water content increased to 90%, the corresponding quantum yields of compounds 2–4 also increased to 30.67%, 45.57% and 26.53%, respectively. Hence, luminogens 2–4 were also AIE-active species. In addition, as shown in Fig. 5, the DFT calculations for the compounds 1–4 were performed. The calculated energy gaps (ΔE) of four compounds were 3.6178416 eV (compound 1), 3.276084 eV (compound 2), 3.3073755 eV (compound 3) and 3.0766347 eV (compound 4) respectively. Therefore, the various numbers and the various kinds of the substituents had slight effects on their molecular orbital energy levels of 1–4.Open in a separate windowFig. 2(a) Fluorescence spectra of the dilute solutions of compound 2 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different water contents (0–90%). Excitation wavelength = 365 nm. (b) Fluorescence images of 2 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different fw values under 365 nm UV light.Open in a separate windowFig. 3(a) Fluorescence spectra of the dilute solutions of compound 3 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different water contents (0–90%). Excitation wavelength = 365 nm. (b) Fluorescence images of 3 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different fw values under 365 nm UV light.Open in a separate windowFig. 4(a) Fluorescence spectra of the dilute solutions of compound 4 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different water contents (0–90%). Excitation wavelength = 365 nm. (b) Fluorescence images of 4 (2.0 × 10−5 mol L−1) in DMF–water mixtures with different fw values under 365 nm UV light.Open in a separate windowFig. 5(a) HOMO and LUMO frontier molecular orbitals of molecule 1 based on DFT (B3LYP/6-31G*) calculation. (b) HOMO and LUMO frontier molecular orbitals of molecule 2 based on DFT (B3LYP/6-31G*) calculation. (c) HOMO and LUMO frontier molecular orbitals of molecule 3 based on DFT (B3LYP/6-31G*) calculation. (d) HOMO and LUMO frontier molecular orbitals of molecule 4 based on DFT (B3LYP/6-31G*) calculation.Subsequently, the mechanochromic fluorescent behaviors of compounds 1–4 were surveyed by solid-state PL spectroscopy. As shown in Fig. 6, the as-synthesized powder sample 1 exhibited an emission band with a λmax at 444 nm, corresponding to a blue fluorescence under 365 nm UV light. Intriguingly, a new blue-green light-emitting band with a λmax at 507 nm was observed after the pristine solid sample was ground. After fuming with dichloromethane solvent vapor for 1 min, the blue-green fluorescence was converted back to the original blue fluorescence. Therefore, luminogen 1 exhibited reversible mechanochromic fluorescence feature. Furthermore, this reversible mechanofluorochromic conversion was repeated many times by grinding-exposure without showing signs of fatigue (Fig. 10).Open in a separate windowFig. 6(a) Solid-state PL spectra of compound 1 before grinding, after grinding, and after treatment with dichloromethane solvent vapor. Excitation wavelength: 365 nm. Photographic images of compound 1 under 365 nm UV light: (b) the as-synthesized powder sample. (c) The ground sample. (d) The sample after treatment with dichloromethane solvent vapor.Open in a separate windowFig. 10Repetitive experiment of mechanochromic behavior for compound 1.Similarly, as evident from Fig. 7–9, luminogens 2–4 also exhibited obvious mechanofluorochromic characteristics. Moreover, the repeatabilities of their mechanochromic behaviors were also satisfactory (Fig. S3†). Hence, all the compounds 1–4 showed reversible mechanofluorochromic phenomena involving different fluorescent color changes, and the various numbers of the substituents could effectively influence the mechanofluorochromic behaviors of 1–4. Obviously, luminogen 3 or 4 after grinding exhibited more red-shifted fluorescence in comparison with that of the corresponding luminogen 1 or 2 after grinding.Open in a separate windowFig. 7(a) Solid-state PL spectra of compound 2 before grinding, after grinding, and after treatment with dichloromethane solvent vapor. Excitation wavelength: 365 nm. Photographic images of compound 2 under 365 nm UV light: (b) the as-synthesized powder sample. (c) The ground sample. (d) The sample after treatment with dichloromethane solvent vapor.Open in a separate windowFig. 8(a) Solid-state PL spectra of compound 3 before grinding, after grinding, and after treatment with dichloromethane solvent vapor. Excitation wavelength: 365 nm. Photographic images of compound 3 under 365 nm UV light: (b) the as-synthesized powder sample. (c) The ground sample. (d) The sample after treatment with dichloromethane solvent vapor.Open in a separate windowFig. 9(a) Solid-state PL spectra of compound 4 before grinding, after grinding, and after treatment with dichloromethane solvent vapor. Excitation wavelength: 365 nm. Photographic images of compound 4 under 365 nm UV light: (b) the as-synthesized powder sample. (c) The ground sample. (d) The sample after treatment with dichloromethane solvent vapor.In order to further explore the possible mechanism of mechanofluorochromism of 1–4, the powder X-ray diffraction (PXRD) measurements of various solid states of 1–4 were carried out. As depicted in Fig. 11, the pristine solid powder 1 showed many clear and intense reflection peaks, suggesting its crystalline phase. However, after the pristine powder sample was ground, the sharp and intense diffraction peaks vanished, which indicated the crystalline form was converted to the amorphous form. Interestingly, when the ground solid sample was fumigated with dichloromethane solvent vapor for 1 min, the corresponding sample powder exhibited the PXRD pattern of the initial crystalline form. Meanwhile, the structural transformations of the solid samples of 2–4 were similar to that of 1 (Fig. S4–S6†). Obviously, the morphological changes of solid samples of 1–4 from crystalline state to amorphous state and vice versa could be attributed to the reversible mechanical switching in compounds 1–4, and the mechanofluorochromic phenomena observed in 1–4 were related to the morphological transition involving the ordered crystalline phase and the disordered amorphous phase.Open in a separate windowFig. 11XRD patterns of compound 1: unground, ground and after treatment with dichloromethane solvent vapor.Fortunately, single crystals of compounds 1 and 2 were obtained by slow diffusion of n-hexane into a trichloromethane solution containing small amounts of 1 or 2. As shown in Fig. 12 and ​and13,13, the molecular structures of 1 and 2 exhibited a twisted conformation due to the existence of tetraphenylethene unit. Meanwhile, some weak intermolecular interactions, such as C–H⋯π interaction (d = 2.866 Å) for 1, π⋯π interaction (d = 3.371 Å) for 1, C–H⋯S interaction (d = 2.977 Å) for 2, and π⋯π interaction (d = 3.189 Å) for 2, were observed. These weak intermolecular interactions gave rise to a loose packing motif of 1 or 2, which indicated their ordered crystal packings might readily collapse upon exposure to external mechanical stimulus. Therefore, their solid-state fluorescence could be adjusted by mechanical force.Open in a separate windowFig. 12The structural organization of compound 1.Open in a separate windowFig. 13The structural organization of compound 2.In summary, four fluorescent molecules containing thiophene and tetraphenylethene units were successfully designed and synthesized in this study. All these compounds showed obvious AIE characteristics. Furthermore, these luminogens emitted various fluorescence colors involving blue-green, green, yellow and orange in the aggregation state. Meanwhile, these luminogens basing on the same core structure also exhibited reversible mechanofluorochromic phenomena involving different fluorescent color changes. The results of this study will be beneficial for the exploitation of novel luminophors with full-color emission.  相似文献   

20.
Effect of moderate magnetic fields on the surface tension of aqueous liquids: a reliable assessment     
Masayuki Hayakawa  Jacopo Vialetto  Manos Anyfantakis  Masahiro Takinoue  Sergii Rudiuk  Mathieu Morel  Damien Baigl 《RSC advances》2019,9(18):10030
We precisely measure the effect of moderate magnetic field intensity on the surface tension of liquids, by placing pendant drops inside uniform fields where bulk forces due to gradients are eliminated. The surface tension of water is unaffected while that of paramagnetic salt solutions slightly decreases with increasing field strength.

A novel setup measures the effect of magnetic field intensities on the surface tension of liquids placed inside uniform fields.

Controlling the properties of fluids in a contactless manner, through the use of external stimuli, offers great advantages in a variety of applications where liquid solutions are involved. Especially, the on-demand variation of their surface/interfacial tension has been proved to be a very efficient method for their handling and manipulation, both in microfluidic channels, or on open surfaces.1 For this purpose, various stimulations have been used, such as thermal,2 electrical3 or optical.4–9 In addition, magnetic control has been proved to be suitable for many practical operations, thanks to its various advantages,10,11 such as: (i) dropping the need of specific substrate modification, (ii) its relative insensitivity to the variation of solution properties (e.g. pH, temperature, ionic concentration, turbidity), (iii) its non-invasive and remote character, and (iv) the good spatio-temporal control. On one hand, fluid manipulation using magnetic fields has been typically performed by adding magnetic particles into the liquids.12–17 Despite being a powerful technique, the use of magnetic particles decreases its applicability, increases costs, and causes sample contamination. On the other hand, for complex fluid handling in microfluidic devices, building up surface tension gradients has already been proved to be suitable in controlling various fluidic operations. Even though intense research effort has been put on studying the magnetic effect on the properties and behaviour of water or other liquids,18–21 only a few studies on their surface tension were reported.22–25 This is true especially for relatively low magnetic fields,26,27 as the one that can be produced with small permanent magnets used inside microfluidic chips (∼100 mT).Up to now, surface tension measurements have always been performed using the pendant drop method, with drops placed in a non-homogeneous magnetic field. The pendant drop is the most commonly used method to determine the interfacial tension of liquid/liquid or liquid/gas interfaces.28 It is based on analysing the shape of drops hanging from a capillary, and deducing the surface tension value with a mathematical model which considers that the drop shape is dictated by the interplay of the forces acting on the drop (surface tension and gravity). However, a non-homogeneous magnetic field exerts an additional bulk force on the liquid drop that causes its deformation.20,29 Such magnetic force will be attractive if the liquid is paramagnetic (having a magnetic susceptibility χ > 0), while it will be repulsive if the liquid is diamagnetic (χ < 0). This interaction can deform the pendant drop in a way that is not considered by the software used for analysis. In these conditions, fitting the drop shape does not allow to distinguish between the bulk and the eventual surface effects. With such an approach, only an apparent surface tension can be detected by the instrument.27,30 In order to suppress the bulk component, which arises in the presence of a magnetic gradient, we constructed an experimental setup where surface tension measurements were performed using the pendant drop method inside highly uniform magnetic fields. Unlike ferrofluid drops that can elongate along field lines due to their strong magnetic response,31 most common liquid drops maintain their shape under uniform fields. Therefore, with our experimental setup, the drop deformation was essentially due to surface effects only and fitting its shape allowed us to accurately extract its surface tension. By varying the field intensity, we could reliably establish the effect of magnetic field on the evolution of surface tension of various diamagnetic and paramagnetic solutions (water and aqueous solutions containing dissolved paramagnetic salts). Fig. 1 shows the two experimental setups used to measure the surface tension of aqueous solutions by means of the pendant drop technique. Fig. 1A shows a sketch of the configuration used to measure the apparent surface tension of drops in a non-homogeneous magnetic field generated by a small permanent magnet placed below the drop. This geometry is similar to the one commonly reported in literature.26,27,32 It has been used in order to compare our experiments with published results, and with the surface tension of the same solutions as measured in a homogeneous magnetic field of similar intensity. Fig. 1B shows the measured map of the magnetic field norm (|B|) around a drop in this configuration. Both the components of the magnetic field perpendicular and parallel to the magnet surface were highly non-homogeneous at the drop level (Fig. S1A and B†), resulting in a variation in |B| of around 70 mT from the drop neck to its bottom. In order to obtain a magnetic field that is homogeneous over the whole drop volume, a novel setup was developed (Fig. 1C). We placed the drop at a precisely controlled distance between two large-sized parallel magnetic plates facing their opposite poles. It is important to note that permanent magnets of this size, when facing each other at relatively short distances (in the order of centimetres) exert a very strong attractive force. Therefore, a rigid scaffold was constructed in order to keep the two magnets at a controlled distance. This set-up was conceived to be compatible with a KRÜSS tensiometer for surface tension measurements. All components used (e.g., syringes and pipette tips) were non-metallic in order to avoid interactions with the strong magnets. In this way, a drop could be produced in the centre of the two parallel magnet surfaces, where both the perpendicular and parallel components of the magnetic field were highly homogeneous (Fig. S1C and D†). Fig. 1D shows the measured map of |B| when the distance between the magnet surfaces and the centre of the drop was d = 5 cm. In that case, the |B| value around the drop was equal to 141 ± 0.5 mT. Varying d allowed us to tune the magnetic field intensity while keeping the field highly homogeneous at the drop region (Fig. S2†).Open in a separate windowFig. 1Experimental setups and measured maps of the magnetic field around a pendant drop. (A) Sketch of a pendant drop in a non-homogeneous magnetic field generated by a small permanent magnet placed below the drop. The distance between the magnet surface and the centre of the drop was d = 10 mm. (B) Map of the measured magnetic field norm (|B|) around the drop in (A). (C) Sketch of a pendant drop in a homogeneous magnetic field generated by two permanent magnets placed parallel to each other, each at a distance d = 5 cm from the drop centre. (D) Map of the measured magnetic field norm (|B|) around the drop in (C). The indicated x, y, z coordinates refer to all (A–D) panels. Drawings of the drop contours (to scale) are shown in (B) and (D) for helping visualizing the drop position in the magnetic field.All experiments were conducted at controlled room temperature and humidity (T = 22.3 ± 0.4 °C; relative humidity = 31.4 ± 5.8%). For each sample, the air/water surface tension values were obtained by averaging measurements over at least ten different drops. The apparent surface tension (γ*) calculated by the tensiometer software of a diamagnetic and a paramagnetic liquid measured in a non-homogeneous magnetic field are reported in Fig. 2A. The diamagnetic liquid is pure water, having a volumic magnetic susceptibility χ = −9.5 ± 0.4 × 10−6; the paramagnetic sample is an aqueous HoCl3 solution at a concentration of 100 mM, with χ = 45 ± 1.7 × 10−6 (Fig. S3†). The actual surface tension (γ) of those liquids, in the absence of the magnetic field, is reported on the left side of the graph. We note that the addition of HoCl3 induced a weak surface tension decrease of the aqueous solution. Approaching a small permanent magnet from the bottom (Fig. 2A, middle) up to a distance d = 10 mm (corresponding magnetic field map in Fig. 1B) caused a deformation of the drop as outlined above: a diamagnetic drop was repelled (compressed), whereas a paramagnetic one was attracted (elongated).Open in a separate windowFig. 2Apparent surface tension (γ*) and surface tension (γ) measurements for diamagnetic and paramagnetic liquids. (A) Apparent surface tension (γ*) measurements for water (violet circles) and a solution of 100 mM HoCl3 (blue triangles) in the absence of a magnetic field (left), with a small permanent magnet approached from the bottom (centre) at a distance d = 10 mm (see Fig. 1 for a map of the corresponding magnetic field), and with a small magnet approached from the side at a distance d = 10 mm. Note that γ* in (A) without the magnet (left side), is an actual surface tension value (γ = γ*). (B) Surface tension (γ) measurements for water (violet circles) and solutions of increasing HoCl3 concentration as a function of the norm of the magnetic field at the drop level. The map of the magnetic field in Fig. 1 corresponds to the points at |B| = 140 mT. Symbols and error bars show mean ± SD from 10 individual experiments.Upon fitting of the drop profiles, the software of the instrument detected an apparent surface tension variation that was quantified as Δγ* = 0.5 mN m−1 for pure water (violet circles, Fig. 2A), and Δγ* = −1.2 mN m−1 for 100 mM HoCl3 (blue triangles). Similar Δγ* values in a non-homogeneous magnetic field were reported in ref 27 both for water and a paramagnetic solution (in their case 200 mM aqueous solution of FeCl3).To show that the change in the apparent surface tension, detected for compressed and elongated drops, was due to a bulk magnetic effect and not to a variation of the surface properties of the solutions in the presence of the magnetic field, we placed the magnet at the same distance from the drop, but on its side, so that the magnetic field gradient pointed from the left to the right side of the drop. As a result, the drop was repelled (pure water) or attracted (100 mM HoCl3 solution), but no compression or elongation occurred. Consequently, the apparent surface tension detected in this configuration (Fig. 2A, right) was the same as without the magnetic stimulation for both solutions. We thus conclude that a setup where a pendant drop is placed in a non-homogeneous magnetic field is not appropriate for measuring the actual effect of the magnetic field on the surface tension.To rule out bulk effects that interfere with the measurements, and to quantify the effect of the magnetic field intensity on surface tension, we performed measurements using the setup depicted in Fig. 1C. Fig. 2B shows the surface tension measured when a drop of a diamagnetic or paramagnetic solution is placed inside a homogeneous magnetic field of varied intensities. We quantified the maximum surface tension variation as Δγ = γ0 − γ140, where γ0 and γ140 were the surface tension without magnetic stimulation, and at the maximum magnetic field intensity used (|B| = 140 mT), respectively. For pure water (violet circles in Fig. 2B) we obtained Δγ = −0.1 mN m−1, a decrease that was smaller than our experimental error. We can therefore conclude that, under moderate magnetic fields up to 140 mT, no magnetic effect on the surface tension was detected. We do not exclude that significant surface tension variation can occur at higher magnetic field intensities, as reported, for example, in ref. 23 and 25 where a magnetic field two orders of magnitude stronger than ours, (10 T) was employed.A similar result, Δγ = −0.1 mN m−1, was also obtained for diamagnetic aqueous solutions composed of 1 mM and 10 mM HoCl3 (χ = −8.4 × 10−6 and χ = −3.4 × 10−6, respectively, see Fig. S3†). When a paramagnetic drop composed of 100 mM HoCl3 was placed inside the homogeneous magnetic field, the maximum surface tension difference measured was Δγ = −0.46 mN m−1. Such amplitude is of similar order of magnitude to that caused by small temperature changes. For instance, the surface tension of water typically varies as Δγ = −0.1 mN m−1 K−1.33 We can therefore conclude that a 100 mM HoCl3 paramagnetic solution shows only a very small decrease of its surface tension in a moderate, homogeneous, magnetic field.  相似文献   

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