Nano-Fe3O4@walnut shell/Cu(ii) as a highly effective environmentally friendly catalyst for the one-pot pseudo three-component synthesis of 1,3-oxazine derivatives under solvent-free conditions

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium. A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines were synthesized by the one-pot pseudo three-component reaction of β-naphthol, formaldehyde and various amines using nano-Fe₃O₄@walnut shell/Cu(ii) at 60 °C under solvent-free conditions. The catalyst was removed from the reaction mixture by an external magnet and was reusable several times without any considerable loss of its activity. This protocol has several advantages such as excellent yields, short reaction times, clean and convenient procedure, easy work-up and use of an eco-friendly catalyst.

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium.

Biopolymers, especially cellulose and its derivatives, have some unparalleled properties, which make them attractive alternatives for ordinary organic or inorganic supports for catalytic applications.¹ Cellulose is the most abundant natural material in the world and it can play an important role as a biocompatible, renewable resource and biodegradable polymer containing OH groups.² Walnut shell is a natural, cheap, and readily available source of cellulose. Fe₃O₄ nanoparticles are coated with various materials such as surfactants,³ polymers,^4,5 silica,⁶ cellulose⁷ and carbon⁸ to form core–shell structures. Magnetic nanoparticles as heterogeneous supports have many advantages such as high dispersion in reaction media and easy recovery by an external magnet.⁹ Cu(ii) as a safe and ecofriendly cation is a good Lewis acid and can activate the carbonyl group for nucleophilic addition reactions.¹⁰1,3-Oxazines moiety has gained great attention from many organic and pharmaceutical chemists due to their broad range of biological activities such as anticancer,¹¹ anti-bacterial,¹² anti-tumor¹³ and anti-Parkinson''s disease.¹⁴Owing to the biological importance of benzo-fused 1,3-oxazines, various methods have been developed for the synthesis of these compounds. Some shown protocols for the synthesis of various 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines via a Mannich type condensation between a 2-naphthol, formaldehyde and a primary amine were reported. This protocol has been catalyzed by KAl(SO₄)₂·12H₂O (alum),¹⁵ ZrOCl₂,¹⁶ polyethylene glycol (PEG),¹⁷ thiamine hydrochloride (VB₁)¹⁸ and CCl₃COOH.¹⁹ Other methods of synthesis of oxazines are aza-acetalizations of aromatic aldehydes with 2-(N-substituted aminomethyl) phenols in the presence of an acid as catalyst²⁰ and electrooxidative cyclization of hydroxyamino compounds.²¹However, some of these catalysts have limitations such as inefficient separation of the catalyst from reaction mixtures, unrecyclable and environmental limitations. Therefore, the development of green and clean methodology for the preparation of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine derivatives is still an interesting challenge.Herein, we wish to report the preparation of Fe₃O₄@nano-walnut shell/Cu(ii) as a new and bio-based magnetic nanocatalyst and its using for one-pot synthesis of 1,3-oxazine derivatives via condensation of β-naphthol, primary amine and formaldehyde.     

Preparation of Ni-microsphere and Cu-MOF using aspartic acid as coordinating ligand and study of their catalytic properties in Stille and sulfoxidation reactions

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies. The Ni-microsphere and Cu-MOF with aspartic acid, as the coordinating ligand, were prepared via a solvothermal method. The morphology and porosity of the obtained Ni microsphere and Cu-MOF were characterized by XRD, FTIR, TGA, DSC, BET and SEM techniques. The catalytic activity of the Ni-microsphere and Cu-MOF was examined in Stille and sulfoxidation reactions. The Ni microsphere and Cu-MOF were easily isolated from the reaction mixtures by simple filtration and then recycled four times without any reduction of catalytic efficiency.

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies.

Cross-coupling reaction is one of the most significant methods to create carbon–carbon bonds in organic synthesis. There are many approaches, including, Suzuki, Stille, and Sonogashira cross-coupling reactions, which are well recognized and highly applicable in organic synthesis. Among them, the Stille reaction, which is an increasingly versatile tool for the formation of carbon–carbon bonds, involves the coupling of aryl halides with organotin reagents.¹ However, these reactions generally require expensive transition metal catalysts such as Pd.² Therefore, it is necessary to develop a new economic, green, and efficient methodology to reduce the environmental impact of the reaction. They are also important intermediates in organic chemistry and have been widely used as ligands in catalysis. The direct oxidation of sulfides is an important method in organic chemistry. Besides, they are also valuable synthetic intermediates for the construction of chemically and biologically important molecules, which usually synthesized by transition metal complexes.³ In this regard, different transition metal complexes of mercury(ii) oxide/iodine,⁴ oxo(salen) chromium(v),⁵ rhenium(v) oxo,⁶ H₅IO₆/FeCl₃,⁷ Na₂WO₄/C₆H₅PO₃H₂,⁸ chlorites and bromites,⁹ NBS¹⁰etc. have been introduced as catalysts. However, these catalysts have several drawbacks; including, separation problems from the reaction medium, harsh reaction conditions, and generating a lot of waste. In order to solve these drawbacks, of separation and isolation of expensive homogeneous catalysts is the heterogenization of homogeneous catalysts and generation of a new heterogeneous catalytic system. Metal–organic frameworks (MOFs) are a class of porous crystalline materials, which show great advantages, i.e. their enormous structural and chemical diversity in terms of high surface area,^11,12 pore volumes,¹³ high thermal,¹⁴ and chemical stabilities,¹⁵ various pore dimensions/topologies, and capabilities to be designed and modified after preparation.¹⁶ In this sense, it is worth mentioning that these features would result in viewing these solids as suitable heterogeneous catalysts for organic transformations.^17–22 MOFs materials are prepared using metal ions (or clusters) and organic ligands in solutions (i.e. solvothermal or hydrothermal synthesis). MOF structures are affected by metal and organic ligands, leading to have more than 20 000 different MOFs with the largest pore aperture (98 Å) and lowest density (0.13 g cm⁻³).²³ Generally, surface area and pore properties of MOFs seem quite dependent on their metal and ligand type as well as synthesis conditions and the applied post-synthesis modifications. The largest surface area was measured in Al-MOF (1323.67 m² g⁻¹)^24,25 followed by ZIF-8-MOF (1039.09 m² g⁻¹),²⁶ while the lowest value was with Zn-MOF (0.86 m² g⁻¹),²⁷ followed by γ-CD-MOF (1.18 m² g⁻¹)²⁸ and Fe₃O(BDC)₃ (7.6 m² g⁻¹).²⁹ Microspheres are either microcapsule or monolithic particles, with diameters in the range (typically from 1 μm to 1000 μm),²⁹ depending on the encapsulation of active drug moieties. In this regard, there are two types of microspheres: microcapsules, defined, as spherical particles in the size range of about 50 nm to 2 mm and micro matrices.³⁰ Microsphere structures have recently attracted much attention due to their unique properties, such as large surface area,³¹ which make them suitable for tissue regenerative medicine,³²i.e. as cell culture scaffolds,³³ drug-controlled release carriers³⁴ and heterogeneous catalysis.³⁵ Many chemical synthetic methods has been developed for their synthesis, including seed swelling,³⁶ hydrothermal or solvothermal methods,³⁶ polymerization,³⁷ spray drying³⁸ and phase separation.³⁹ Among these methods, the solvothermal synthesis has been used as the most suitable methodology to prepare a variety of nanostructural materials, such as wire, rod,⁴⁰ fiber,⁴¹ mof⁴² and microsphere.⁴³ In this sense, the synthesis process involves the use of a solvent under unusual conditions of high pressure and high temperature.⁴⁴ The properties of microspheres are highly dependent on the number of pores, pore diameter and structure of pore.⁴⁵ The degree of porosity depends on various factors such as temperature, pH, stirring speed, type, and concentration of porogen, polymer, and its concentration.⁴⁶ There have been numerous studies to investigate the coordination behavior of a ligand with different metals under the same conditions.^47–49 Herein, we aim at comparing the catalytic behavior of Ni-microsphere and Cu-MOF with aspartic acid as the coordinating ligand in Stille and sulfoxidation reactions (Scheme 1).Open in a separate windowScheme 1(a) Schematic synthesis of Ni microsphere and Cu-MOF and their application as catalyst (b) topological structure of Cu-MOF (c) topological of Ni microsphere.     

E–Z isomerization of 3-benzylidene-indolin-2-ones using a microfluidic photo-reactor

Here, we report controlled E–Z isomeric motion of the functionalized 3-benzylidene-indolin-2-ones under various solvents, temperature, light sources, and most importantly effective enhancement of light irradiance in microfluidic photoreactor conditions. Stabilization of the E–Z isomeric motion is failed in batch process, which might be due to the exponential decay of light intensity, variable irradiation, low mixing, low heat exchange, low photon flux etc. This photo-μ-flow light driven motion is further extended to the establishment of a photostationary state under solar light irradiation.

(E)-3-Benzylidene-indolin-2-ones were efficiently converted to their corresponding (Z) -isomers at low temperature in the presence of light.

Functionalized 3-benzylidene-indolin-2-ones are an important structural motif in organic chemistry and are embedded in many naturally occurring compounds.¹ They found wide applications in molecular-motors,² energy harvesting dyes,³ pharmaceutical chemistry (sunitinib, tenidap),⁴ protein kinase inhibitors,⁵ pesticides,⁶ flavors,⁷ and the fragrance industry.⁸ In the last few decades, numerous protocols have been developed for the synthesis of novel indolin-2-ones. For instance, palladium (Pd)-catalysed intramolecular hydroarylation of N-arylpropiolamides,⁹ Knoevenagel condensation of oxindole and aldehyde,¹⁰ two-step protocols such as Ni-catalyzed CO₂ insertion followed by coupling reaction,¹¹ Pd-catalysed C–H functionalization/intramolecular alkenylation,¹² Pd(0)/monophosphine-promoted ring–forming reaction of 2-(alkynyl)aryl isocyanates with organoboron compound, and others.¹³Knoevenagel condensation is one of the best methods for the preparation of 3-benzylidene-indolin-2-ones, but often it gives mixture of E/Z isomeric products. Otherwise, noble metal-catalysed protocols received enormous interest. However, the limited availability, high price, and toxicity of these metals diminished their usage in industrial applications. Therefore, several research groups have been engaged in search of an alternative greener and cleaner approach under metal-free conditions. To address the diastereoisomeric issue, Tacconi et al. reported a thermal (300–310 °C) isomerization reaction of 3-arylidene-1,3-dihydroindol-2-ones,¹⁴ which suffers from poor reaction efficiency and E/Z selectivity. Therefore, transformations controlling E/Z ratio of 3-benzylidene-indolin-2-ones remains a challenging task and highly desirable (Scheme 1).Open in a separate windowScheme 1Functionalized 3-benzylidene-indolin-2-ones and alkenes in bioactive compounds and the accessible methods.On the other hand, selective E/Z stereo-isomerization of alkenes has been well established using various methods in the presence of light stimuli,^15a cations,^15b halogens or elemental selenium,¹⁶ palladium-hydride catalyst,¹⁰ cobalt-catalyst,¹⁷ Ir-catalyst,¹⁸ organo-catalysts.¹⁹ Among these, light-induced photostationary E/Z stereoisomerization is very attractive, due to its close proximity towards the natural process. In recent years, several light-driven molecular motors (controlled motion at the molecular level), molecular propellers,²⁰ switches,²¹ brakes,²² turnstiles,²³ shuttles,²⁴ scissors,²⁵ elevators,²⁶ rotating modules,²⁷ muscles,²⁸ rotors,²⁹ ratchets,³⁰ and catalytic self-propelled objects have been developed.³¹ Further, equipment''s relying on molecular mechanics were rapidly developed, particularly in the area of health care.Till date, controlled photo-isomerization of functionalized 3-benzylidene-indolin-2-ones is one of the puzzling problems to the scientific community. Photochemical reactions in batch process have serious drawbacks with limited hot-spot zone due to inefficient light penetration with increasing light path distance through the absorbing media, and the situation becomes poorer when the reactor size increases.^32,33 In contrast, the capillary microreactor platform has emerged as an efficient the artificial tool with impressive advantages, such as excellent photon flux, uniform irradiation, compatibility with multi-step syntheses, excellent mass and heat transfer, which lead to significant decrease the reaction time with improved yield or selectivity over batch reactors.^33a,34 To address the aforementioned challenges, it is essential to develop a highly efficient photo-microchemical flow approach for the controlled isomerization of functionalized 3-benzylidene-indolin-2-ones in catalyst-free and an environment friendly manner.     

Nanozyme-based catalytic theranostics

Nanozymes, a type of nanomaterial with intrinsic enzyme-like activities, have emerged as a promising tool for disease theranostics. As a type of artificial enzyme mimic, nanozymes can overcome the shortcomings of natural enzymes, including high cost, low stability, and difficulty in storage when they are used in disease diagnosis. Moreover, the multi-enzymatic activity of nanozymes can regulate the level of reactive oxygen species (ROS) in various cells. For example, superoxide dismutase (SOD) and catalase (CAT) activity can be used to scavenge ROS, and peroxidase (POD) and oxidase (OXD) activity can be used to generate ROS. In this review, we summarize recent progress on the strategies and applications of nanozyme-based disease theranostics. In addition, we address the opportunities and challenges of nanozyme-based catalytic theranostics in the near future.

With its diverse physical–chemical properties and highly efficient enzyme-like activities, nanozymes have been widely used in various theranostics.

A nanozyme is a type of nanomaterial (1–100 nm) with enzyme-like activities.^1,2 It can catalyze the reaction of enzyme substrates under physiological conditions, and it has similar catalytic efficiency and enzymatic abilities to natural enzymes. Our previous work found that Fe₃O₄ nanoparticles (NPs) possess an intrinsic peroxidase (POD)-like activity.³ Since then, numerous nanomaterials have been discovered to have POD-, catalase (CAT)-, superoxide dismutase (SOD)-, or oxidase (OXD)-like catalytic activities.⁴ A nanozyme may have more than one type of catalytic activity.⁵ Nowadays, more than 540 nanozymes from 49 elements have been reported from 350 laboratories in 30 countries.^6,7 Among these, iron oxide nanoparticles,⁸ CeO₂,⁹ graphene oxide,¹⁰ carbon nanozymes¹¹ and gold nanoparticles¹² are widely studied and applied.Nanozymes can simulate the catalytic processes of natural enzymes and regulate the redox level of cells, especially on reactive oxygen species (ROS). ROS are intermediate products which emerge in the process of oxygen metabolism, mainly including superoxide anion (O₂˙⁻), hydroxyl radical (·OH), and hydrogen peroxide (H₂O₂).¹³ An abnormal rise in ROS level will destroy the homeostasis of redox in vivo and cause oxidative stress. Nanozymes typically exhibit multiple enzymatic activities. On the one hand, the catalase and superoxide dismutase activity of nanozymes are mainly used to regulate the intracellular ROS level, which plays an important role in protecting cells. On the other hand, the oxidase and peroxidase activity of nanozymes induce ROS production and promote apoptosis, such as in cancer cells.With advantages such as high catalytic efficiency, high stability, biosafety, low cost and easy preparation,¹⁴ nanozymes have been widely used in industrial, medical, and biological fields and in environmental remediation.^2,15,16 Currently, a variety of nanozyme-based biomedical applications have been extensively explored, including biosensors,¹⁷in vitro texts,¹⁸ and antimicrobial¹⁹ and disease treatments, such as cancer therapy, bone marrow therapy and wound healing.²⁰ Here, we summarize the biomedical applications of nanozymes in vivo, as well as addressing the opportunities and challenges of nanozyme-based catalytic disease theranostics in the near future.     

Liquid phase assisted grain growth in Cu2ZnSnS4 nanoparticle thin films by alkali element incorporation

The effect of adding LiCl, NaCl, and KCl to Cu₂ZnSnS₄ (CZTS) nanoparticle thin-film samples annealed in a nitrogen and sulfur atmosphere is reported. We demonstrate that the organic ligand-free nanoparticles previously developed can be used to produce an absorber layer of high quality. The films were Zn-rich and Cu-poor, and no secondary phases except ZnS could be detected within the detection limit of the characterization tools used. Potassium was the most effective alkali metal to enhance grain growth, and resulted in films with a high photoluminescence signal and an optical band gap of 1.43 eV. The alkali metals were introduced in the form of chloride salts, and a significant amount of Cl was detected in the final films, but could be removed in a quick water rinse.

We present a route where organic ligand-free, KCl-functionalized Cu₂ZnSnS₄ nanoparticles grow into large, dense grains during annealing in nitrogen/sulfur atmosphere.

Thin-film photovoltaic materials with an absorber layer consisting of either CuInGaSe₂ (CIGS) or CdTe exhibit high power conversion efficiencies of 22.6% and 22.1%, respectively, and are already available on the solar panel market.¹ However, due to the relatively poor abundance of In, Ga, and partly Te, as well as the toxicity of Cd, it is important to look for substituting compounds, and here Cu₂ZnSnS₄ (CZTS) is a promising alternative. CZTS has reached a record efficiency of 9.5%,¹ and it has a high absorption coefficient of >10⁴ cm⁻¹ and a direct band gap of 1.45–1.51 eV, which furthermore also makes it an interesting material for a tandem solar cell with silicon.²For solution-processed CZTS, the current record efficiency for a nanoparticle solar cell is 4.8%,³ while devices made from molecular/precursor inks approach 6%.⁴ For the molecular precursor route, the synthesis step is circumvented, which should favor this method. It is, however, still important to develop the nanoparticle approach, as it allows a higher concentration of CZTS in the ink, and therefore facilitates different deposition techniques. As it is yet unknown which method will work best for future upscaling it is important to have different technologies.One challenge for the nanoparticle approach is to obtain uniform grain growth during the annealing step.³ CZTS nanoparticles are typically synthesized with long hydrocarbons as ligands/surfactants, e.g. oleylamine (OLA). After annealing thin films consisting of these particles, the formation of large grains on the surface can be observed, while a fine-grain layer is formed at the bottom interface.^3,5,6 This fine-grained material contains carbon, and its effect on the solar cell is not known. Even with ligands consisting of shorter hydrocarbon chains,⁶ the annealed CZTS nanoparticle film will remain porous. Therefore, it seems that solid state material diffusion which promotes grain growth is very slow under the specific annealing conditions.Grain growth in the form of sintering is desired as it can result in a dense film. In sintering particles are merged at a temperature below the melting point, and it occurs to minimize the surface area and thus the surface energy of a colloidal system.^7,8 The rate of sintering can be increased by hot pressing, impurity doping to enhance grain boundary diffusion, or incorporating an element that becomes a liquid phase at elevated temperature, i.e. liquid phase reactive sintering.^7,8For solution-processed CZTS, both hot-pressing⁹ and including a dopant have been attempted with promising film morphologies. Typically, the alkali metals Na and K are used, but promising results have also been achieved for Li and Sb. The incorporation of these elements has been done through a selection of different processes. For precursor CZTS films, the dopants can be incorporated directly in the ink, which has resulted in some of the highest efficiencies to date when using Sb(OAc)₃ and NaCl.⁴ A common way to include these elements in nanoparticle films is by soaking the film in a sodium salt solution,⁵ or depositing a thin NaF layer on top of the absorber before annealing, which adds an extra vacuum-deposition step;³ for both methods, the beneficial effects of the incorporated elements is typically restricted to the close proximity of the surface, and limited by its diffusion within the film.¹⁰ To obtain a more uniform distribution of incorporated dopants, the surface of the nanoparticles can be functionalized with e.g. SbCl₃,¹¹ or CF₃COONa.¹⁰We have previously reported a one-step synthesis of organic ligand-free nanoparticles, which minimizes the amount of organic material in the film, allows for using solvents like water and ethanol, and furthermore makes it possible to directly dissolve controllable amounts of various chloride salts in the ink.^12,13 In this paper we investigate the effect of LiCl, NaCl, and KCl on the structural evolution and opto-electronic properties of these thin films.     

Yield stress fluids and fundamental particle statistics

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers. Probability distribution functions are determined for canonical ensembles of volumes displaced at the incipient motion in three representative states (single, double, and multiple occupancies). The statistical average points out an effective solid fraction by which the yield stress behavior is satisfactorily described in a number of aqueous (Si₃N₄, Ca₃(PO₄)₂, ZrO₂, and TiO₂) and non-aqueous (Al₂O₃/decalin and MWCNT/PC) disperse systems. Interestingly, the only two model coefficients (maximum packing fraction and stiffness parameter) turn out to be correlated with the relevant suspension quantities. The latter relates linearly with (Young’s and bulk) mechanical moduli, whereas the former, once represented versus the Hamaker constant of two particles in a medium, returns a good linear extrapolation of the packing fraction for the simple cubic cell, here recovered within a relative error ≈ 1.3%.

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers.

Yield stress fluids form a particular state of matter,¹ displaying non-linear and novel visco-plasto-elastic flow dynamics upon different boundary conditions. As their name says, they don’t flow until a certain load, the so-called yield stress (or point, τ₀), is applied. This value may be generally interpreted as a shear stress threshold for the breakage of interparticle connectivity.² Furthermore, as it initiates motion in the system, it is connected to mechanical inertia³ and particle settling, i.e. it is a terse summary of buoyancy, dynamic pressure, weight, viscous and yield stress resistances.⁴ For prototype systems such as colloids dispersed in a liquid, yield points sensibly depend on the mechanism by which the solid phase tends to interact or aggregate.^5–8 The macroscopic constitutive equations they obey, such as the Herschel–Bulkley model, were shown to correspond, over a four-decade range of shear rates, to the local rheological response.⁹From the side of an experimenter, however, unambiguously defining a yield stress may not always be straightforward. It can be affected by the experimental procedure adopted, always considering a measurement or some extrapolation technique with the limit of zero shear. Conversely, unyielded domains may be defined by areas where the shear stress second invariant falls below the yield value, plus some small semi-heuristic constant.¹⁰ In addition, theoretically, the meaning of notions like τ₀ and rheological yielding were questioned to be only qualitative or even to stand for an apparent quantity.¹¹ The dependence they generally show on timescales characteristic of the applied (mechanical) disturbance, also suggested an intimate relationship¹² between yield stress and dispersion thixotropy.¹³ On the other hand, assigning a hydrodynamic or mechanical state below the yield point to a material that is not flowing seems not to be scientifically sound. Experimental values are normally obtained by extrapolation of limited data, whereas careful measurements below the yield point would actually imply that flow takes place.¹⁴At any rate, the analysis of properly defined τ₀ concepts forms the subject of interesting investigations and is still a powerful tool in many applications, including macromolecular suspensions,¹⁵ gels, colloidal gels and organogels,^16–18 foams, emulsions and soft glassy materials.¹⁹ It allows for effective comparisons between the resistances which fluids initially oppose to the shear perturbation, somehow specifying a measure of the particle aggregation states taking place in a given dispersant. Electrorheological materials, for instance, exhibit a transition from liquid-like to solid-like behaviors, which is often examined by a yield stress investigation upon a given fluid model (e.g. the Bingham model or the Casson model).^20,21 The combination of yield stress measurements with AFM techniques can be used to well-characterize the nature of weak particle attractions and surface forces at nN scales.⁸ Further issues of a more geometrical nature, which naturally connect to τ₀, are rheological percolation²² and its differences from other connectivity phenomena, such as the onset of electric²³ or elastic percolation.^24,25 In granular fluids, it relates with the theory of jammed states,²⁶ originally pioneered by Edwards.²⁷In nanoscience as well, the stability control and characterization in single and mixed dispersions or melts is an important and complex step.^28,29 Carbon nanotube suspensions,³⁰ for example, can be prepared in association with other molecular systems, like surfactants and polymers^31–33 or by (either covalent or non-covalent) functionalization of their walls with reactive groups, which increases the chemical affinity with dispersing agents.³⁴ As a consequence of large molecular aspect ratios and significant van der Waals’s attractions, the nanotube aggregation is highly enhanced, giving rise to strongly anisotropic systems of crystalline ropes and entangled network bundles, which are difficult to exfoliate, suspend or even characterize.³⁵ Stable CNT dispersions of controlled molecular mass may also exhibit polymeric behavior, and be quantitatively studied by equations taken from the well-established science of macromolecules.^36,37This paper puts forward a basic approach, mostly focused on equilibrium arguments, to devise a yield stress law connected with particle statistics. By conjecturing an ensemble of effective volumes ‘displaced’ at the incipient state of motion, a statistical mechanics picture of τ₀ is proposed. This affords a phenomenological hypothesis that can be developed with reasonable simplicity. The derived relations are applied to typical disperse systems in colloid science and soft matter, such as aqueous and nonaqueous suspensions of ceramic/metal oxides and nanoparticles.     

Synthesis of novel benzopyran-connected pyrimidine and pyrazole derivatives via a green method using Cu(ii)-tyrosinase enzyme catalyst as potential larvicidal,antifeedant activities

A series of benzopyran-connected pyrimidine (1a–g) and benzopyran-connected pyrazole (2a–i) derivatives were synthesized via Biginelli reaction using a green chemistry approach. Cu(ii)-tyrosinase was used as a catalyst in the synthesis of compounds 1a–g and 2a–ivia the Biginelli reaction. The as-synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. The as-synthesized compounds were screened for larvicidal and antifeedant activities. The larvicidal activity was evaluated using the mosquito species Culex quinquefasciatus, and the antifeedant activity was evaluated using the fishes of Oreochromis mossambicus. The compounds 2a–i demonstrated lethal effects, killing 50% of second instar mosquito larvae when their LD₅₀ values were 44.17, 34.96, 45.29, 45.28, 75.96, and 28.99 μg mL⁻¹, respectively. Molecular docking studies were used for analysis based on the binding ability of an odorant binding protein (OBP) of Culex quinquefasciatus with compound 2h (binding energy = −6.12 kcal mol⁻¹) and compound 1g (binding energy = −5.79 kcal mol⁻¹). Therefore, the proposed target compounds were synthesized via a green method using Cu(ii)-enzyme as a catalyst to give high yield (94%). In biological screening, benzopyran-connected pyrazole (2h) was highly active compared with benzopyran-connected pyrimidine (1a–g) series in terms of larivicidal activity.

Cu(ii)-tyrosinase catalytic help with the synthesis of benzopyran-connected pyrimidine and pyrazole derivatives and their larvicidal activity.

Benzopyrans (coumarins) are an important group of naturally occurring compounds widely distributed in the plant kingdom and have been produced synthetically for many years for commercial uses.¹ In addition, these core compounds are used as fragrant additives in food and cosmetics.² The commercial applications of coumarins include dispersed fluorescent brightening agents and as dyes for tuning lasers.³ Some important biologically active natural benzopyran (coumarin) derivatives are shown in Fig. 1. Mosquitoes are the vectors for a large number of human pathogens compared to other groups of arthropods.⁴ Their uncontrollable breeding poses a serious threat to the modern humanity. Every year, more than 500 million people are severely affected by malaria. The mosquito larvicide is an insecticide that is specially targeted against the larval life stage of a mosquito. Particularly, the compound bergapten (Fig. 1), which shows the standard of larivicidal activity,⁵ is commercially available, and it was used as a control in this study for larvicidal screening. Moreover, the antifeedant screening defense mechanism makes it a potential candidate for the development of eco-friendly ichthyocides. Coumarin derivatives exhibit a remarkably broad spectrum of biological activities, including antibacterial,^6,7 antifungal,^8–10 anticoagulant,¹¹ anti-inflammatory,¹² antitumor,^13,14 and anti-HIV.¹⁵Open in a separate windowFig. 1Biologically active natural benzopyran compound.Coumarin and its derivatives can be synthesized by various methods, which include the Perkin,¹⁶ Knoevenagel,¹⁷ Wittig,¹⁸ Pechmann,¹⁹ and Reformatsky reactions.Among these reactions, the Pechmann reaction is the most widely used method for the preparation of substituted coumarins since it proceeds from very simple starting materials and gives good yields of variously substituted coumarins. For example, coumarins can be prepared by using various reagents, such as H₂SO₄, POCl₃,²⁰ AlCl₃,²¹ cation exchange resins, trifluoroacetic acid,²² montmorillonite clay,²³ solid acid catalysts,²⁴ W/ZrO₂ solid acid catalyst,²⁵ chloroaluminate ionic liquid,²⁶ and Nafion-H catalyst.²⁷Keeping the above literature observations, coumarin derivatives 1a–g and 2a–i are usually prepared with the conventional method involving CuCl₂·2H₂O catalysis with using HCl additive. This reduces the yield and also increases the reaction time. To overcome this drawback, we used mushroom tyrosinase as a catalyst without any additive, a reaction condition not reported previously. The as-synthesized compounds were used for the biological screening of larvicidal and antifeedant activities (marine fish). In addition, in this study, we considered the molecular docking studies study based on previous studies for performing the binding ability of hydroxy-2-methyl-4H-pyran-4-one (the root extract of Senecio laetus Edgew) with the odorant binding protein (OBP) of Culex quinquefasciatus.²⁸     

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond.

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors.

The 1,2,4-thiadiazinane 1,1-dioxide motif can be found in many biologically active compounds for vastly different medical conditions. For example, verubecestat (1) has been in phase III clinical trials as a β-amyloid precursor protein cleaving enzyme (BACE 1) inhibitor to treat moderate and prodromal Alzheimer''s disease.¹ Ribizzi et al. have shown that taurolidine (2) displays cytotoxic activity against certain human tumour cells,² but primarily it is used as an antibacterial agent.³ In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders.⁴ 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods;^5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition.^14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.^16–18 The literature on this reagent describe it as a connector molecule,¹⁹ and a warhead in chemical biology.^20–22 There are only four publications that, so far, have reported the use of α,β-unsaturated sulfonyl fluoride based compounds as starting materials in organic synthesis.^23–26 Based on our earlier experience with the reactivity of aryl α,β-unsaturated sulfonyl fluoride towards various amine nucleophiles¹⁷ (Scheme 1), we hypothesized that an α,β-unsaturated sulfonyl fluoride of type 4 can possibly be explored for the synthesis of thiadiazinanes. This hypothesis was based on observation of low amounts of the six-membered product was formed along with the major β-sultam product 5 when p-nitrophenylethenesulfonyl fluoride was subjected to excess methyl amine in methylene chloride as a solvent and triethylamine as additional base at room temperature (Scheme 1).Open in a separate windowScheme 1Formation of 1,2,4-thiadiazinane 1,1-dioxides, along with β-sultams, when aryl ethenesulfonyl fluorides are subjected to large excess of primary amines in DCM as solvent and DBU as catalyst.The reactivity of dichloromethane (DCM) as a methylene donor was unfamiliar to us at the time, but a literature survey quickly revealed that organic solvents (DMF,²⁷ DMSO,^28–30 CHCl₃ (ref. 31 and 32) and CH₂Cl₂ (ref. 33 and 34)) have proved to be more than solvents. DCM has indeed been reported to act as a bis-electrophilic methylene donor in the presence of strong bases and nucleophiles³³ (e.g. carboxylic acids,³⁵ thiols,³⁶ amines, etc.). DCM may also form hydrochloride salts,³⁷ aminals,³⁸ and quaternary salts³⁹ when reacted with tertiary and secondary amines. These reactions were reviewed by Mills et al.⁴⁰ and the kinetics of the reaction of DCM with pyridine was documented by Rudine et al.⁴¹ Liu and co-workers reported formation of methylene-bridged 3,3′-bis-(oxazolidin-2-one) through reaction of oxazolidin-2-ones with DCM and sodium hydride.⁴² Cui et al. reported the synthesis of bispidine with the utilisation of DCM as a C1 unit.⁴³ Dipyrrolidylmethane CH₂(pyr)₂ and dipiperidylmethane, CH₂(pip)₂ were synthesized via the condensation of the secondary amine precursors and DCM at room temperature in the absence of light.⁴⁴ Another reaction of amines with methylene chloride yielded aminals rapidly.⁴⁵ Matsumoto et al. reported the reaction of DCM with ketones or esters in the presence of secondary amines at high pressure whereby DCM was used as methylene bridge in forming both C–C and C–N bonds.⁴⁶ Zhang and co-workers also published the formation of simultaneous carbon–carbon bond and carbon-nitrogen bonds whereby DCM acted as a synthon in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and a copper catalyst.⁴⁷     

Rapid separation and purification of lead halide perovskite quantum dots through differential centrifugation in nonpolar solvent

We report the rapid separation and purification of lead halide perovskite quantum dots (QDs) in a nonpolar solvent by using a convenient and efficient differential separation method. Size-selective precipitation effectively separates the perovskite QDs from larger aggregates and provides direct evidence for strong quantum confinement in the photoluminescence (PL). Significantly, the size-selected perovskite QDs are readily well-dispersed in a nonpolar solvent and remain stable in ambient air (humidity > 60%) for >20 days. These enable measurement of the electronic band structure of versatile perovskite QDs as a function of size for the first time. Despite a clear blue-shift of the optical bandgap, the lowest unoccupied molecular orbital (LUMO) readily moves towards the vacuum level while the highest occupied molecular orbital (HOMO) changes slightly, in good agreement with that observed in the quantum size effect tuning of quasi-2D perovskites and colloidal semiconductor QDs. The results demonstrate the possibility of utilizing differential centrifugation as a novel method to attain size-dependent tunability for property-specific perovskite-QD based optoelectronic applications.

We introduce differential separation as an efficient method for preparing monodisperse fractions of versatile halide perovskite quantum dots with tunable sizes, enabling investigations of their size-dependent electronic band structure properties.

Halide perovskites (ABX₃, X = Cl, Br, or I) are among the most intensively studied semiconductor materials offering unique electrical and optical properties that are particularly demanded in versatile optoelectronic applications such as lasers, light-emitting diodes (LEDs), photodetectors and solar cells.^1–5 In contrast to conventional semiconductor materials such as Si and Ge,^6,7 the optical properties of halide perovskites can be readily tuned by adjusting their components, i.e., halide content, yielding strong photoluminescence (PL) across the whole visible spectrum.⁸ It has been recognized that bright and efficient blue emission plays a key role in the development of halide perovskite LEDs. Current progress in blue perovskite LEDs largely benefits from the component engineering for bandgap tuning, i.e., using mixed halide perovskites.^9,10 Although green and red LEDs incorporating halide perovskites have shown remarkable external quantum efficiency (EQE) over 20%,^11,12 the fabrication of efficient and stable blue LEDs remains challenging largely due to the fact that the blue-emitting perovskites using mixed halide ions usually suffer from severe ion migration and phase segregation under external excitation of light or bias voltage,^13,14 impeding device performance and thereby the niche market application of perovskite LED technologies. Nevertheless, such a challenge may be confronted by taking advantage of the size-dependent tunability of optical properties in terms of the quantum size effect, i.e., quantum dots (QDs).^15,16 The quantum size effect describes changes in the electronic band structure of a semiconductor as a result of reduction in the dimensionality below a certain threshold.^17–19 The quantum confinement, on one hand, gives rise to a blue-shift of the PL energy. On the other hand, it also causes perovskite QDs to emit light much more efficiently than their bulk counterparts.^20,21To meet the requirement of perovskite optoelectronic technologies, effective technical methods to attain size-tunable monodisperse perovskite QDs are still highly desired. To date, many approaches have been developed for synthesizing various kinds of halide perovskite QDs. Kovalenko et al. reported a facile hot injection method for colloidal synthesis of CsPbX₃ QDs with cubic shape and cubic perovskite crystal structure.²² Dong et al. reported a ligand-assisted re-precipitation colloidal strategy to prepare brightly luminescent and color-tunable CH₃NH₃PbX₃ perovskite QDs with high quantum yields and low excitation fluencies.²³ Petrozza et al. demonstrated the synthesis of ligand-free CH₃NH₃PbX₃ perovskite QD inks that are suitable for large-area processing by laser ablation.²⁴ Ogale et al. showed the synthesis of perovskite quantum structures by using an electrospray technique in conjunction with an antisolvent–solvent extraction.²⁵ However, many of the synthetic methods produce perovskite QD suspensions with poor morphology and considerable size polydispersity.²⁶ Consequently, a complex post-synthesis size-purification process is usually required, resulting in significant loss of the perovskite QD products.²⁷Nanoseparation represents an important and effective complementary process to prepare monodisperse nanoparticles for size-dependent electrical and optical properties.^28,29 In particular, differential separation is a centrifugal method based on the different settling velocity of nanoparticles in a homogeneous media that has been widely used especially for the separation and extraction of nanoparticles which contain a big weight difference between the fragments.³⁰ The separation and purification of metal nanoparticles and typical colloidal semiconductor QDs such as Si and CdSe in organic density gradient have been demonstrated by using differential centrifugation.^29,31,32 However, there have been very few attempts to separate perovskite QDs and the preparation of monodisperse perovskite QDs using size-separation methods is still in its infancy. Thus, knowledge with respect to the definite size-dependent electronic band structure properties of perovskite QDs remains incomplete, in contrast to conventional semiconductor QDs.In this work, we employ a room-temperature ligand-mediated transport method which is capable of synthesizing a variety of organic-inorganic and inorganic halide perovskite QDs with strong PL (quantum yields (QYs) up to 90%) including MAPbI₃, MAPbBr₃, FAPbI₃, FAPbBr₃ and CsPbBr₃ QDs (MA = CH₃NH₃, FA = HC(NH₂)₂).³³ The obtained perovskite QDs suspended in the crude solutions are surface-terminated by long alkyl chains such as oleic acid and octylamine. We then introduce differential separation as a straightforward and efficient experimental method for preparing monodisperse fractions of perovskite QDs with tunable sizes. Our results reveal that the selection of proper solvents with low polarity is the key for realizing rapid separation and purification of perovskite QDs through differential centrifugation. The size-selected perovskite QDs remained in nonpolar solvents such as hexane and exhibit stable and tunable PL with small band width under ambient air conditions, enabling investigations of their size-dependent electronic band structure properties which is crucial to the development of property-specific perovskite-QD based optoelectronic applications.³⁴     

Organocatalytic sulfa-Michael/aldol cascade: constructing functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter

A practical sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylates has been developed, which allows efficient access to functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter in moderate to good yields with high enantioselectivities.

A sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylate has been developed, which allows access to 2,5-dihydrothiophenes bearing a quaternary carbon center in moderate to good yields with high enantioselectivities.

Among the various classes of heterocycles, members of the thiophene family have received particular attention from the chemical community because of their widespread occurrence as ubiquitous motifs in natural products, pharmaceuticals, agrochemicals as well as materials.¹ In this context, the 2,5-dihydrothiophene ring is a common structural feature of many bioactive compounds and a potential intermediate for various synthetic applications.² Over the decades, only a few examples of the assembly of optically active 2,5-dihydrothiophenes have been documented.³ For instance, the Spino^3b group successfully prepared non-racemic dihydrothiophenes using an efficient chiral auxiliary. The first gold-catalyzed cycloisomerization of α-hydroxyallenes to 2,5-dihydrothiophenes was reported by Krause^3c and co-workers. Then in 2010, the Xu^3e group developed a highly stereoselective domino thia-Michael/aldol reaction between 1,4-dithiane-2,5-diol and α,β-unsaturated aldehyde catalyzed by a chiral diphenylprolino TMS ether, which provided a new avenue for the synthesis of functionalized 2,5-dihydrothiophenes.Quaternary carbon stereocenters are often contained in natural products and pharmaceuticals.⁴ Compared with the chiral pool synthesis,⁵ the procedure of chiral materials or catalysts to construct such sterically congested stereogenic centers is more challenging because of the difficulty of orbital overlap.⁶ To date, a lot of progresses have been made in the construction of chiral quaternary carbon centers in cyclic compounds,⁷ which are greatly accelerated by the advancement of transition metal catalysis,⁸ and organocatalysis,⁹ including methods beyond radical initiation.¹⁰ However, only few examples are about the construction of a quaternary carbon in 2,5-dihydrothiophene ring.¹¹ Inspired by the previous work of the Xu group,^3e we describe herein an elegant organocatalytic asymmetric cascade sulfa-Michael/aldol reaction, providing a convenient way for the synthesis of 2,5-dihydrothiophenes bearing a chiral quaternary cabon center.     

Improved performance and stability of perovskite solar cells with bilayer electron-transporting layers

Zinc oxide nanoparticles (NPs) are very promising in replacing the phenyl-C₆₁-butyric acid methyl ester (PC₆₁BM) as electron-transporting materials due to the high carrier mobilities, superior stability, low cost and solution processability at low temperatures. The perovskite/ZnO NPs heterojunction has also demonstrated much better stability than perovskite/PC₆₁BM, however it shows lower power conversion efficiency (PCE) compared to the state-of-art devices based on perovskite/PCBM heterojunction. Here, we demonstrated that the insufficient charge transfer from methylammonium lead iodide (MAPbI₃) to ZnO NPs and significant interface trap-states lead to the poor performance and severe hysteresis of PSC with MAPbI₃/ZnO NPs heterojunction. When PC₆₁BM/ZnO NPs bilayer electron transporting layers (ETLs) were used with a device structure of ITO/poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine) (PTAA)/MAPbI₃/PC₆₁BM/ZnO NPs/Al, which can combine the advantages of efficient charge transfer from MAPbI₃ to PC₆₁BM and excellent blocking ability of ZnO NPs against oxygen, water and electrodes, highly efficient PSCs with PCE as high as 17.2% can be achieved with decent stability.

Perovskite solar cells with PC₆₁BM/ZnO nanoparticles bilayer electron-transporting layers were achieved with a power conversion efficiency of 17.2% and decent stability.

Organic–inorganic hybrid perovskite solar cells (PSCs) have recently attracted tremendous attention because of their excellent photovoltaic efficiencies.^1–4 Since the initial results published in 2009 with efficiencies about 4% using a typical dye-sensitized solar cell structure with liquid electrolyte,⁵ significant progress has been made in device performance through developing high quality film processing methods,^6–10 tuning the perovskite composition,^11–15 optimizing the device architectures^16,17 and synthesizing new hole/electron transport materials.^18–21 Recently, a certified record power conversion efficiency (PCE) of 22.7% was achieved.²² Despite of the success in obtaining dramatically improved PCE, there are certain concerns about the stability and cost towards commercialization. For the state-of-the-art PSCs, perovskites are susceptible to degradation in moisture and air, thus the charge transport materials should prevent the perovskite from exposure to such environments.^20,23–25 One the other hand, PSCs also suffer from the high cost of widely used organic charge transport materials such as 2,2,7,7-tetrakis(N,N-di-p-methoxyphenylamine)-9,9-spirobifluorene (spiro-OMeTAD), phenyl-C_61/71-butyric acid methyl ester (PC_61/71BM).^3,18,26 As alternatives, inorganic materials such as CuSCN,²⁷ CuI,²⁸ CuGaO₂,²⁰ and NiO_x ^29,30 which can be acted as hole transport materials and ZnO,^31,32 SnO₂ ^12,33,34 and TiO₂ ^10,35 which can be acted as electron transport materials are widely studied. Among them, metal oxide nanoparticles (NPs) are very promising in replacing the organic counterparts due to the high carrier mobilities, superior stability, low cost and solution processability at low temperatures.^16,31,33The perovskite/ZnO NPs heterojunction has been demonstrated much better stability than perovskite/PCBM,²³ however it shows lower PCE compared to the state-of-art devices based on perovskite/PCBM heterojunction.^36–38 Thus in this paper, we systematically studied the charge transfer and recombination at CH₃NH₃PbI₃ (MAPbI₃) and ZnO NPs or PC₆₁BM interfaces and tried to fabricate devices with high PCE and super stability simultaneously. We demonstrated that insufficient charge transfer from MAPbI₃ to ZnO NPs and significant interface trap-states lead to the poor performance and severe hysteresis of PSCs based on MAPbI₃/ZnO NPs heterojunction, while the devices based on MAPbI₃/PC₆₁BM show high PCE and negligible hysteresis due to the efficient charge transfer from MAPbI₃ to PC₆₁BM and less recombination at the interface. On the other hand, the MAPbI₃/ZnO NPs devices show excellent stability in air because of the excellent capping ability of ZnO NPs while the stability of MAPbI₃/PC₆₁BM devices is very poor. Thus, we fabricated the PSCs with bilayer electron-transporting layers (ETLs) with the device structure of ITO/poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine) (PTAA)/MAPbI₃/PC₆₁BM/ZnO NPs/Al, trying to combine the advantages of efficient charge extraction ability of PC₆₁BM and excellent blocking ability of ZnO NPs against oxygen, water and electrode, and finally device with PCE as high as 17.2% was achieved with decent stability.     

NIR-triggered upconversion nanoparticles@thermo-sensitive liposome hybrid theranostic nanoplatform for controlled drug delivery

Posterior segment ocular diseases are highly prevalent worldwide due to the lack of suitable noninvasive diagnostic and therapeutic tactics. Herein, concerning this predicament, we designed a hybrid retina-targeted photothermal theranostic nanoplatform (UCNPs@Bi@SiO₂@GE HP-lips), based on the unique upconversion luminescence (UCL) imaging of upconversion nanoparticles (UCNPs), efficient photothermal conversion ability of Bi nanoparticles, and thermal-induced phase transition properties of the liposomes (lips). The nanoplatform was functionalized with penetratin (PNT) and hyaluronic acid (HA), to obtain retina-targeted liposomes (HP-lips). Lipophilic genistein (GE) was entrapped into the liposomes (GE HP-lips). An in vitro release study showed NIR irradiation could photothermally trigger controlled release of GE from the liposomal platform. Moreover, cellular uptake evaluation via UCL imaging demonstrated UCNPs@Bi@SiO₂@GE HP-lips represented the brightest UCL, compared with other formulations, which is beneficial for the accurate evaluation of the prognosis and severity of angiogenesis-related posterior segment disorders. Therefore, UCNPs@Bi@SiO₂@GE HP-lips exhibit promising potential as a theranostic nanoplatform for posterior segment ocular diseases.

A novel hybrid photothermal theranostic nanoplatform UCNPs@Bi@SiO₂@GE HP-lips is developed. Upon NIR irradiation, the nanoplatform could photothermally trigger controlled drug release and present bright upconversion luminescence.

Posterior segment ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), have drawn considerable attention worldwide. Both AMD and DR are highly prevalent and have been proven to be the leading causes of blindness in the developed nations, resulting in a heavy social burden.^1,2 It is common sense that neovascularization in the posterior segment, including choroidal neovascularization (CNV) and retinal neovascularization (RNV), is the primary cause of severe visual impairment.³ Research has shown that suitable therapeutic tactics, as well as timely and precise diagnostic avenues, are highly crucial to the prevention and/or treatment of angiogenesis-related ocular disorders. Therefore, it is high time to develop proper platforms with desirable diagnostic and therapeutic abilities for angiogenesis-related ocular disorders.For accurate evaluation of the prognosis and severity of angiogenesis-related posterior segment disorders, convenient and efficient imaging techniques of angiogenesis are the prerequisites. Diverse nanoprobes for bioimaging are one of the best fruits of the quick development of nanotechnology.^4–7 Many organic imaging agents have been employed in the field of bioimaging.^8–10 Besides organic bioimaging agents, inorganic lanthanide (Ln³⁺)-doped upconversion nanoparticles (UCNPs), which can convert low-energy NIR light into higher-energy UV/visible/NIR light, have attractive superiorities over conventional organic dyes and quantum dots, such as high signal-to-noise ratio, low auto-fluorescence background, narrow emission peak width, superb stability, and absence of photodamage to live organisms.^7,11,12 Accordingly, UCNPs have been broadly investigated as emerging luminescent nanoprobes for real-time bioimaging and drug release tracking in recent decades.^13,14 Especially, NIR light shows an adequate penetration depth in deep tissue, which promotes in vivo bioimaging application of UCNPs.¹⁵ Additionally, UCNPs have been widely employed as a building block to construct multimodal imaging nanoplatforms to enhance their imaging precision or equipped with therapeutic functionality by surface functionalization, designing hierarchical nanostructures with other functional nanoparticles and introducing diversiform doped ions.^16,17 Rieffel et al. have designed porphyrin–phospholipid-coated UCNPs, realizing at least six imaging modalities, including upconversion luminescence imaging, fluorescence imaging, positron emission tomography, computed tomography, photoacoustic imaging, and Cerenkov luminescence imaging.¹⁸ To integrate the photothermal function into UCNPs, diverse UCNPs-based nanocomposites with different nanostructure have been developed, such as UCNPs-Au,¹⁹ UCNPs-CuS,²⁰ UCNPs-Cu₂S,²¹ UCNPs-Ag₂S,²² and UCNPs-Bi₂Se₃.¹⁶ These nanocomposites structurally combining UCNPs with photothermal agents would not only achieve real-time monitoring of in vivo agent distribution, but can also endow UCNPs with photothermal therapeutic ability. Numerous studies of UCNPs-based nanoplatforms for diagnosis and therapy of tumors present an undeniable interest in the biomedical application of UCNPs.^5,23–25 Very recently, UCNPs have been utilized in the field of ophthalmic application. Ma et al. designed retinal photoreceptor-binding upconversion nanoparticles (pbUCNPs) and endowed the mice with NIR light image vision while their normal vision and related behavioral responses were not compromised.²⁶ Microenvironment-triggered degradable hydrogels were designed by Li et al. using ultrasmall UCNPs, and exhibited its potential application in non-invasive NIR-II imaging diagnosis and combined therapy in human choroidal melanoma.²⁷Current therapeutic strategies of angiogenesis-related ocular disorders are far from satisfactory. It is universally acknowledged that intraocular injection of anti-vascular endothelial growth factor (VEGF) agents has been broadly accepted as a “gold standard” treatment for angiogenesis-related ocular diseases and in a way, can ameliorate the visual impairment of DR and AMD patients.²⁸ Nonetheless, repeated invasive injections enhance the risk of complications, compromise patient compliance, and aggravate the burden of healthcare.²⁹ Topical instillation of eye drops is the most common and accessible route to treat ocular diseases due to its convenient and painless properties, however, multiple ocular barriers (including cornea, conjunctiva, sclera, blood-retinal barrier, and blood-aqueous barrier) result in a negligible permeated amount of drug to the posterior segment by topical administration.² Recently, photo-driven therapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have been widely used in biomedicine and many organic components play key roles.^30,31 Additionally, light has been widely employed as a non-invasive external stimulus for remote spatiotemporal controlled drug release.^7,32 Light-triggered drug delivery platforms exhibit attractive advantages, including low cost, outstanding therapeutic effect and little damage to physiological tissue, and hence are suitable for non-invasive ocular drug delivery, in terms of intrinsic anatomical and biological constraints of eyes. It is reported that cell penetrating peptides (CPPs), which can promote the transport of various cargos across the cell membrane, have evoked considerable interest in pharmaceutical applications.^33,34 Among the peptides, penetratin (PNT), a cationic and amphipathic CPP, was demonstrated to have excellent penetration through multiple physiological barriers in the eyes, promoting drug transport to the posterior segment.^35,36 Angiogenesis-related posterior segment diseases can result in the overexpression of cluster of differentiation 44 (CD44) in the retina.^37,38 As we all know, hyaluronic acid (HA) is a specific ligand of the CD44 receptor. Accordingly, HA can be applied as a retina-targeted ligand for posterior ocular drug delivery. In short, PNT and HA are ideal constituent parts to design retina-targeted theranostic nanoplatforms towards diagnosis and therapy for angiogenesis-related posterior ocular diseases.Herein, we designed a hybrid photothermal stimuli-responsive theranostic nanoplatform, UCNPs@Bi@SiO₂@GE HP-lips with the retina-targeted ability (Fig. 1), to realize the combined diagnosis and therapy for angiogenesis-related posterior diseases. Genistein (GE), an anti-angiogenic agent that could suppress CNV formation, was selected as the model drug.³⁹In vitro release study revealed UCNPs@Bi@SiO₂ in the aqueous core of the liposomal platform could generate mild heat upon NIR irradiation, which facilitated phase transition of thermo-sensitive phospholipid DPPC, enhanced the fluidity of lipid layer, and hence triggered the release of GE from the liposomal platform. The admirable cytocompatibility of the nanocomposites with ARPE-19 cells was demonstrated by CCK-8 assay and live/dead cell staining. Moreover, UCL imaging proved cellular uptake of the nanocomposites by ARPE-19 cells was time-dependent and UCNPs@Bi@SiO₂@HP-lips showed the brightest UCL, compared with other formulations. Therefore, UCNPs@Bi@SiO₂@GE HP-lips could be a potential theranostic nanoplatform for posterior segment diseases.Open in a separate windowFig. 1Schematic diagram of UCNPs@Bi@SiO₂@GE HP-lips for NIR-triggered drug release. (A) The fabrication procedure of UCNPs@Bi@SiO₂@GE HP-lips. As proposed, hydrophilic UCNPs@Bi@SiO₂ and lipophilic drug GE were loaded in the aqueous core and lipid bilayer of the liposome frameworks, respectively. Cell penetrating peptide PNT and retina-targeted ligand HA were conjugated by amidation reaction in the preformed liposome bilayer. (B) Upon NIR irradiation, UCNPs@Bi@SiO₂ in the aqueous core of the liposomal platform could generate mild heat, which realized real-time green UCL monitoring and photothermally triggered drug release.     

Correction: Nano N-TiO2 mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes

Correction for ‘Nano N-TiO₂ mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes’ by Kaliyamoorthy Selvam et al., RSC Adv., 2012, 2, 2848–2855, DOI: 10.1039/C2RA01178F.

The authors regret omitting citations of their related papers in Journal of Molecular Catalysis A: Chemical and Applied Catalysis A: General: ‘Cost effective one-pot photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂’ (DOI: 10.1016/j.molcata.2011.09.014)¹ and ‘Mesoporous nitrogen doped nano titania—A green photocatalyst for the effective reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol’ (DOI: 10.1016/j.apcata.2011.11.011).² The citations should have appeared in the following places as ref. 36 (ref. 1, in the reference list here) and ref. 37 (ref. 2, in the reference list here):In the sentence starting on line 5 of paragraph 5 in the introduction:‘Photocatalytic synthesis of quinolone derivatives from nitrobenzene using TiO₂, metal doped TiO₂ and others had been reported earlier.^1,23–25’At the end of Section 3.12 with the addition of the following sentence:‘This catalyst was also found to be effective for the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol.²’The authors regret that it was not clear in the original article that the bare TiO₂ and N-TiO₂ characterisation data had been reproduced from their related Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 Although the Catalysis Communications article was cited as ref. 25 (ref. 3, in the reference list here) in the original article, it was not made clear that some of the data was reproduced from this article. The appropriate figure captions have been updated to reflect this.Fig. 2: Diffuse reflectance spectra of (a) bare TiO₂, (b) N-TiO₂ and (c) TiO₂-P25. The bare TiO₂ data in Fig. 2a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 2b have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 3: Photoluminescence spectra of (a) bare TiO₂, (b) TiO₂-P25 and (c) N-TiO₂. The bare TiO₂ data in Fig. 3a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 3c have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 4: HR-TEM analysis: (a and b) images at two different regions of N-TiO₂, (c) SAED pattern of N-TiO₂, (d) lattice fringes of N-TiO₂ and (e) particle size distribution of N-TiO₂. Fig. 4 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 5: X-ray photoelectron spectra of N-TiO₂: (a) survey spectrum, (b) Ti 2p peak, (c) O 1s peak, (d) N 1s peak and (e) C peak. Fig. 5 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 6: (a) N₂ adsorption–desorption isotherms of N-TiO₂ and (b) its pore size distribution. Fig. 6 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 8: GC-MS chromatograms at different reaction times for the photocatalytic conversion of nitrobenzene with N-TiO₂. Fig. 8 has been entirely reproduced with permission from ref. 3. Copyright 2011 Elsevier.The authors also wish to remove Fig. 1 from the original article due to similarities between two of the spectra and the raw data no longer being available. This does not affect the conclusions as the presence of nitrogen was confirmed by other techniques.The authors also wish to clarify the differences between this RSC Advances paper and the Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 The Journal of Molecular Catalysis A: Chemical paper discusses the photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂.¹ The Applied Catalysis A: General paper reports the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles using mesoporous nitrogen doped nano titania.² The Catalysis Communications paper, ref. 25 in the original article, discusses the synthesis of quinaldines from nitroarenes with gold loaded TiO₂ nanoparticles.³ The original RSC Advances paper discusses the catalytic ability of N-TiO₂ in the synthesis of quinaldines from nitrobenzenes. In each paper, either a different catalyst was used or a different synthetic reaction was investigated.     

Tuning the charge carrier mobility in few-layer PtSe2 films by Se : Pt ratio

Recently, few-layer PtSe₂ films have attracted significant attention due to their properties and promising applications in high-speed electronics, spintronics and optoelectronics. Until now, the transport properties of this material have not reached the theoretically predicted values, especially with regard to carrier mobility. In addition, it is not yet known which growth parameters (if any) can experimentally affect the carrier mobility value. This work presents the fabrication of horizontally aligned PtSe₂ films using one-zone selenization of pre-deposited platinum layers. We have identified the Se : Pt ratio as a parameter controlling the charge carrier mobility in the thin films. The mobility increases more than twice as the ratio changes in a narrow interval around a value of 2. A simultaneous reduction of the carrier concentration suggests that ionized impurity scattering is responsible for the observed mobility behaviour. This significant finding may help to better understand the transport properties of few-layer PtSe₂ films.

This work presents the fabrication of horizontally aligned PtSe₂ films using one-zone selenization of pre-deposited platinum layers. We have identified the Se : Pt ratio as a parameter controlling the charge carrier mobility in the thin films.

Any material used in high-speed electronics needs to fulfil basic requirements, including a high current on/off switch ratio and high charge carrier mobility for fast operation.¹ Layered 2D transition metal dichalcogenide (TMDC) materials with tuneable band gap and transitional behaviour have considerable potential in this area.² TMDCs contain over 40 combinations of transition metal and chalcogenides.³ Platinum diselenide (PtSe₂) belongs to a group of noble-TMDCs, which naturally occurs in the 1T phase.⁴ PtSe₂ has been predicted as an exceptional material, and in addition, experiments proved its outstanding properties, such as widely tuneable band gap, air stability and high carrier mobility. Single-layer to few-layer PtSe₂ is a p-type semiconductor, thicker or bulk PtSe₂ shows a semi-metallic character.^5,6 It has been confirmed, that PtSe₂ also has optoelectronic performance⁷ and photocatalytic activities.^5,6 This extends its possible applications in photodetection⁸ or quick-response gas sensing.^9,10 Avsar et al.¹¹ showed that atomic-scale defects could transform non-magnetic 2D crystals into magnetic phases. Using first-principles calculations they suggest that a platinum vacancy defect yields antiferro- (ferro-) magnetic ordering in mono- (bi-) layer PtSe₂. For all the applications mentioned above, high quality and large-area PtSe₂ films are necessary.Several possible fabrication methods of monolayer and few-layer PtSe₂ have been developed. Yan et al. used molecular beam epitaxy to create high-quality epitaxial thin PtSe₂ films with a controllable thickness.¹² This method is outstanding for creating large-size single-crystalline films on various substrates. On the other hand, this method is less suitable for large-scale device fabrication. Chemical vapour deposition^13,14 and direct selenization of thin platinum films (also called thermally assisted conversion-TAC)^6,15 are extensively used to fabricate PtSe₂ films on the nanometres thickness range. This method is suitable for preparing large-area films. However, nanocrystals are oriented randomly, yet no long-range ordering within the layer has been experimentally achieved. This is one of the limiting factors for much lower charge carrier mobility than it was predicted.As we have already mentioned above, PtSe₂ is a promising material for application in electronics. The charge carrier mobility of PtSe₂ has been predicted to be one of the highest among TMDCs.¹⁶ However, the experimentally measured carrier mobility of PtSe₂ is much lower than the theoretically predicted value.² The mobility strongly depends on the scattering phenomena within the material. Intrinsic mobility is determined by scattering caused by lattice vibrations.¹ For 2D materials in general, several factors including charge impurity, structural defects or surface optical phonons scattering, dominate the charge transport.^17,18 For example, point defects typically lower the carrier mobility or degrade mechanical properties of 2D materials.¹⁹ Fabrication method also strongly influences the film quality as well as charge carrier mobility values. The highest values were obtained on PtSe₂ flakes peeled off from bulk crystals using a scotch tape-based mechanical exfoliation. Zhao et al.¹⁶ fabricated a few-layer device on SiO₂/Si substrate exhibiting a semiconducting behaviour with high room-temperature electron mobility (210 cm² V⁻¹ s⁻¹) in a back-gated configuration. Xu et al.²⁰ demonstrated the controllable doping in PtSe₂ few-layer films prepared by selenization. Depending on the growth conditions, they fabricated both n-type and p-type PtSe₂ films of various thicknesses.²⁰ The films showed FET mobility of 14 and 15 cm² V⁻¹ s⁻¹ for p-type and n-type FETs, respectively. Selenization of pre-deposited platinum layers leads to PtSe₂ films exhibiting p-type semiconducting behaviour with hole mobility values up to 13 cm² V⁻¹ s⁻¹.²¹ However, after the fabrication of FET structure, the field effect mobility decrease to 0.3 cm² V⁻¹ s⁻¹.This paper presents the fabrication of few-layer PtSe₂ films by one-zone selenization of a pre-deposited platinum layer. We studied how nitrogen flow during the selenization process affects the chemical composition, structural, and electrical transport properties of the final PtSe₂ films. In contrast, the temperature, heating rate, selenization time, and initial thickness of Pt pre-deposited layers were constant. To analyse the structural and chemical properties of prepared PtSe₂ films we used the combination of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Raman spectroscopy. The charge carrier mobility of the samples was determined from the Hall-effect measurement. We found a correlation between the selenium concentration in the sample and its carrier mobility. The charge carrier mobility values scale linearly with Se : Pt ratio close to 2.     

TEMPORAL EVOLUTION AND PREDICTORS OF SUBJECTIVE COGNITIVE COMPLAINTS UP TO 4 YEARS AFTER STROKE

ObjectiveTo examine the temporal evolution of subjective cognitive complaints in the long-term after stroke, and to identify predictors of long-term subjective cognitive complaints.MethodsProspective cohort study including 395 stroke patients. Subjective cognitive complaints were assessed at 2 months, 6 months and 4 years post-stroke, using the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24). The temporal evolution of subjective cognitive complaints was described using multilevel growth modelling. Associations between CLCE-24 cognition score at 4 years post-stroke and baseline characteristics, depression, anxiety, cognitive test performance, and adaptive and maladaptive psychological factors were examined. Significant predictors were entered in a multivariate multilevel model.ResultsA significant increase in subjective cognitive complaints from 2 months up to 4 years (mean 3.7 years, standard deviation (SD) 0.6 years) post-stroke was observed (p≤0.001). Two months post-stroke, 76% of patients reported at least one cognitive complaint, 72% at 6 months, and 89% at 4 years post-stroke. A higher level of subjective cognitive complaints at 2 months and lower scores on adaptive and maladaptive psychological factors were significant independent predictors of a higher level of subjective cognitive complaints at 4 years post-stroke.ConclusionPost-stroke subjective cognitive complaints increase over time and can be predicted by the extent of subjective cognitive complaints and the presence of adaptive and maladaptive psychological factors in the early phases after stroke.LAY ABSTRACTMany people suffer a stroke in the brain leading to consequences in different areas of functioning. Complaints in the domain of thinking (memory, attention, planning and organization) are frequent post-stroke. This study investigated the occurrence and type of complaints experienced in the first years after a stroke. The study found that these complaints increase over time. Longterm complaints are found in those people who already have problems early after stroke.Key words: stroke, rehabilitation, cognition, cognitive complaints

Subjective cognitive complaints (SCC) are common after stroke, with prevalence rates varying between 28.6% (1) and 90.2%, (2), depending on stroke characteristics, time since stroke, SCC definitions and the instruments used. The most commonly reported complaints are mental slowness (in 46–80% of patients) and difficulties in concentration and memory (in 38–68% and 38–94% of patients, respectively) (3). Previous cross-sectional studies showed that SCC are present in both the early stages after stroke (1–6 months after stroke) (4–6), and in the long-term (> 1 year after stroke) (1, 7, 8). To date only a few studies have examined the temporal evolution of SCC. Tinson & Lincoln observed an increase in SCC between 1 and 7 months post-stroke (n = 95) (9). The authors used the Everyday Memory Questionnaire (10), focusing on memory-related complaints. Wilz & Barskova also found an increase in SCC over time after stroke (3 vs 15 months post-stroke, n = 81) (11). SCC were measured with the Patient Competency Rating Scale cognition subscale (12). Van Rijsbergen et al., who used the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24) (13), recently found that SCC remained stable between 3 and 12 months after stroke (n = 155) (14). Long-term results on the course of post-stroke SCC are lacking. Since SCC were found to be independently related to lower quality of life in patients with mild cognitive impairment (15), and patients with subarachnoid haemorrhage (16), it is important to assess SCC after stroke. Furthermore, earlier research showed that SCC were most strongly associated with participation after stroke, compared with cognitive tests in a neuropsychological test battery, and the Montreal Cognitive Assessment (MoCA) (17, 18). Hence, in order to improve participation and integration in society after stroke, it is important to take the patients’ perspective into account, rather than only determining objective cognitive measures.The presence and severity of SCC is expected to be a direct reflection of the presence and severity of cognitive deficits. However, previous studies investigating the relationship between SCC and cognitive performance in stroke patients have shown conflicting results (1–4, 7, 8, 13, 19, 20). Other factors have shown to be related to SCC, in particular psychological factors, such as depressive symptoms (2, 4, 6, 7, 21), anxiety (21, 22), perceived stress (14), personality traits (7, 22), and coping style (23). To date, only one study on SCC used a longitudinal design (14), which prevents conclusions on the temporal evolution of SCC in stroke patients in the long term. Since more stroke patients survive, recover well and are discharged home nowadays, it is important to address predictors of SCC in the early phases after stroke, in order to identify patients who need more intensive monitoring at follow-up. Once identified, it is possible to investigate whether the patients will benefit from more focused rehabilitation programmes.The aim of this longitudinal study was to examine the temporal evolution of SCC, from 2 months until 4 years post-stroke. Furthermore, the study assessed which factors are predictive of SCC at 4 years post-stroke, taking into account demographic and stroke-related characteristics at baseline, and cognitive deficits and psychological factors measured at 2 months post-stroke.     

Synthesis of 3-selanylbenzo[b]furans promoted by SelectFluor®

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans mediate by Selectfluor® reagent. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy.

The benzo[b]furan scaffold is an important structural motif that is present in natural products and in synthetic compounds with therapeutic proprieties.¹ Substituted benzo[b]furans have shown a broad range of biological activities,² being found in a variety of pharmaceutical targets, such as Viibryd® and Ancoron® (Fig. 1).³ These drugs are used for treatment of depression and for cardiac arrhythmias, respectively. An efficient method to obtain substituted benzo[b]furans is the intramolecular cyclization reaction between 2-alkynylphenol or 2-alkynylanisole derivatives with different electrophilic species to generate a wide variety of 3-substituted-benzo[b]furans. This strategy is especially useful because of the atom-economic synthesis under mild conditions.⁴Open in a separate windowFig. 1Substituted benzo[b]furans in commercial drugs.Organoselenium compounds have attracted great interest due the large number of biological applications and their versatile reactivity.⁵ From a synthetic point of view, the ease cleavage of the Se–Se bond in diselenide compounds can generate species with different reactivity, as radical, electrophile, and nucleophile. This ample usefulness becomes the diselenides in key synthetic intermediates to introduce selenium moiety in organic compounds or to catalyse organic transformations.^5,6Despite the recent advances in the synthesis of 3-selanyl-benzo[b]furans, new electrophiles and reactional conditions were explored (Scheme 1).^{7–9,11–15} Initially, the establishing work by Larock and co-workers toward the synthesis of 3-selanyl-benzo[b]furans through the intramolecular cyclization of 2-(phenylethynyl)anisole with PhSeCl in CH₂Cl₂ at room temperature.⁷ In 2009, Zeni and co-workers demonstrated the synthesis of 3-selanyl-benzo[b]furans employing PhSeBr as an active electrophile.⁸ A pioneering protocol was reported by Zeni and co-workers, which employed FeCl₃ (1.0 equiv.) and diorganyl diselenides in CH₂Cl₂ at 45 °C.⁹ Additionally, Lewis acids have been used as effective catalysts in Se–Se bonding cleavage to access functionalized selenium compounds.¹⁰ Afterward, alternative methods were developed, such as the synthesis of 3-selanyl-benzo[b]furans mediated by PdCl₂/I₂, I₂/water, and CuI (1.5 equiv.).^11–14 More recently, Liu and co-workers reported a radical cyclization reaction using selenium powder as selenium source and AgNO₃ as catalyst in DMSO at 100 °C.¹⁵Open in a separate windowScheme 1Methodologies to prepare 3-selanyl-benzo[b]furans.Although, there are different methodologies to prepare 3-selanyl-benzo[b]furans and other functionalized selenium compounds through the reaction between diselenides compounds with oxidant reagents or Lewis acids, alternative electrophilic selenium species should be employed to avoid metals and/or toxic reagents.^9–15 Furthermore, RSeCl and RSeBr,^7,8 obtained from the reaction of diselenides with SO₂Cl₂ (or Cl₂) and Br₂ respectively, are commercially available and largely used as selenylating agent. However, these species present a low stability under moisture, and the high nucleophilicity of chloride and bromide leaving groups can lead to undesirable side reactions.On the other hand, SelectFluor® is a versatile reagent used for different applications, such as fluorination reactions,¹⁶ C–H functionalization¹⁷ and organic function transfer.¹⁸ In addition, SelectFluor® has been used as an efficient method for intramolecular annulation reactions, due its higher reactivity.¹⁹ This ample application together with the desirable characteristics of the SelectFluor®, such as the higher stability, non-hydroscopic solid and hazard-free source of fluorine,²⁰ promoted new possibilities to investigate fluorine chemistry. In 2004, Poleschner and Seppelt prepared PhSeF derivatives by the reaction between diorganyl diselenides and XeF₂ in CH₂Cl₂ as a solvent at −40 °C.²¹ The products were characterized by low-temperature ¹⁹F and ⁷⁷Se NMR, and it was the first confirmation of this type of electrophilic selenium compound. Although electrophilic selenium catalysis (ESC) with electrophilic fluoride reagents as oxidants has been demonstrated in the functionalization of alkenes,²² fewer knowledge about the reactivity of this selenium electrophilic species is available in the literature.²³Based on the development of new electrophilic selenium reagents,^9–14,24 herein, we describe a metal-free synthesis of 3-selanyl-benzo[b]furans under mild conditions using this very reactive electrophilic selenium species (RSe-F), generated in situ at room temperature by the reaction of diorganyl diselenides with SelectFluor® reagent (Scheme 1). Moreover, the higher reactivity of RSe-F species could be explored for the insertion of selenium moiety in other building blocks because the environmentally friendly reactional condition, and the replacing chlorine and bromine by the non-nucleophilic fluorine counter ion, can partially circumvented some side reactions.     

Effects of the halogenido ligands on the Kumada-coupling catalytic activity of [Ni{tBuN(PPh2)2-κ2P}X2], X = Cl,Br, I,complexes

Novel nickel(ii) complexes bearing (^tbutyl)bis(diphenylphosphanyl)amine and different halogenido ligands, [Ni(P,P)X₂] = [Ni{^tBuN(PPh₂)₂-κ²P}X₂], (X = Cl, Br, I) are prepared, characterized by IR and NMR spectroscopy, mass spectrometry and X-ray crystallography, and tested as catalysts in the Kumada cross-coupling reaction of model substituted iodobenzenes and p-tolylmagnesium bromide. The data obtained together with DFT calculations indicate that these new catalysts operate in the Ni(i)–Ni(iii) mode. The highest catalytic activity and selectivity are exhibited by [Ni(P,P)Cl₂], which is most easily reduced by the used Grignard reagent to the Ni(i) state. This process is much more energy demanding in the case of the bromido and iodido complexes, causing the appearance of the induction period. [Ni(P,P)Cl₂] is also very active in the cross-couplings of substrates with iodine atoms sterically shielded by ortho substituents. The data obtained are in good accordance with the described positive effect of the increased electron-releasing power of N-substituents R′ on the overall catalytic performance of [Ni{R′N(PPh₂)₂-κ²P}X₂] complexes.

Novel nickel(ii) complexes [Ni(P,P)X₂] = [Ni{^tBuN(PPh₂)₂-κ²P}X₂], X = Cl, Br, I, are prepared, characterized by IR and NMR spectroscopy, mass spectrometry and X-ray crystallography, and tested as catalysts in the Kumada cross-coupling reaction.

In recent years, the chemical and catalytic properties of transition metal complexes bearing N-functionalized bis(diphenylphosphanyl)amine ligands, R′N(PPh₂)₂, have been under consideration.^1,2 For instance, chromium complexes with this type of ligand are known to oligomerize various olefins.^3–8 In addition, a large number of [M{R′N(PPh₂)₂-κ²P}X₂] complexes, M = Ni, Pd, Pt; X = Cl, Br, I (see Scheme 1), exhibiting small P–M–P bite angles, were recently reviewed.² Selected palladium(ii) complexes bearing X = Cl,^9–14 Br,^14,15 I,^14,16 catalyze the Suzuki–Miyaura and Heck coupling reactions. Some structurally characterized Ni(ii) analogous complexes bearing X = Cl,^17–28 Br,^18,29–37 I,^18,36,38 catalyze polymerization of norbornene^20,21 or oligomerization (X = Br,^32,34 I,³⁸) and polymerization (X = Br²⁹) of ethene. It should be stressed that nickel(ii) complexes of this family are only moderately active catalysts in the Suzuki–Miyaura reaction.³⁵ On the other hand, they exhibit a considerable catalytic activity and acceptable selectivity in the Kumada coupling reaction.^23,35Open in a separate windowScheme 1General structure of the studied complexes [M(P,P)X₂], M = Ni, Pd, Pt; X = Cl, Br, I; R'' = ((S)-CHMePh), (CH₂)₃Si(OCH₃)₃, ^tBu.Kumada coupling is one of the most important C–C coupling reactions³⁹ for a wide range of purposes, including pharmaceutical applications.⁴⁰ Although palladium-based complexes are mostly the first choice catalysts for this coupling,^41–43 complexes of other transition metals such as iron,^44,45 and nickel^46,47 are also used. We have already investigated the catalytic activity of [Ni{R′N(PPh₂)₂-κ²P}X₂], R′ = (S)-CHMePh; X = Cl, Br,³⁵ and R′ = (CH₂)₃Si(OMe)₃; X = Cl,²³ in homogeneous systems to extend the scope of nickel(ii) catalysts in this reaction. The latter catalyst has also been anchored onto mesoporous molecular sieves, thus providing an active heterogenized catalyst.²³ In homogeneous catalytic reactions, both catalysts bearing R′ = (S)-CHMePh) showed a substrate conversion (68% for X = Cl and 63% for X = Br),³⁵ significantly lower compared to that of the catalyst with R′ = (CH₂)₃Si(OMe)₃ and X = Cl (79%).²³ These results suggested that the increased electronegativity of coordinated halogenido ligands and the increased electron-donating power of the R′ moiety have positive effects on the catalytic efficiency of this type of nickel(ii) complexes. In the work presented herein, the effects exerted by the identity of halogenido ligands X⁻ and the R′ moiety on catalytic activity and selectivity were further assessed by exploring three novel complexes, [Ni{^tBuN(PPh₂)₂-κ²P}X₂], X = Cl, Br, I, henceforth referred to as [Ni(P,P)X₂], bearing the strongly electron-releasing ^tbutyl (^tBu) group as R′.     

Mechanism of sulfidation of small zinc oxide nanoparticles

ZnO has industrial utility as a solid sorbent for the removal of polluting sulfur compounds from petroleum-based fuels. Small ZnO nanoparticles may be more effective in terms of sorption capacity and ease of sulfidation as compared to bulk ZnO. Motivated by this promise, here, we study the sulfidation of ZnO NPs and uncover the solid-state mechanism of the process by crystallographic and optical absorbance characterization. The wurtzite-structure ZnO NPs undergo complete sulfidation to yield ZnS NPs with a drastically different zincblende structure. However, in the early stages, the ZnO NP lattice undergoes only substitutional doping by sulfur, while retaining its wurtzite structure. Above a threshold sulfur-doping level of 30 mol%, separate zincblende ZnS grains nucleate, which grow at the expense of the ZnO NPs, finally yielding ZnS NPs. Thus, the full oxide to sulfide transformation cannot be viewed simply as a topotactic place-exchange of anions. The product ZnS NPs formed by nucleation-growth share neither the crystallographic structure nor the size of the initial ZnO NPs. The reaction mechanism may inform the future design of nanostructured ZnO sorbents.

In the sulfidation of small ZnO nanoparticles, the nanoparticles first undergo sulfur doping followed by the nucleation-growth of ZnS domains.

Zinc oxide (ZnO) nanoparticles (NPs), due to their cost-effectiveness and biodegradability, have a multitude of applications^1–3 including coatings^4–8 and pigments,^9,10 catalysis,^11,12 energy storage,^13,14 and environmental remediation.^15–22 ZnO NPs have particular appeal as sorbents for scavenging polluting sulfur compounds such as mercaptans and hydrogen sulfide (H₂S) from petroleum-based fuels:^23–27 ZnO + H₂S → ZnS + H₂O. Lattice O²⁻ in the ZnO is replaced with S²⁻ scavenged from the pollutant. Bulk powders of ZnO have already been used for adsorptive removal of H₂S,^28,29 but NPs have specific advantages. With smaller grain sizes, mass transport limitations are lifted.²³ Whereas sulfidation is limited to the surface of bulk ZnO, with NPs, the entire mass of ZnO can undergo sulfidation, enabling high sorbent capacity.²³ Volume and morphology changes resulting from restructuring of the solid can also be more easily accommodated with NPs,²³ allowing regenerable use of the sorbent. Finally, the high specific surface area of NPs allows more enhanced kinetics of the sulfidation reaction, potentially facilitating much lower desulfurization temperatures as compared to the conventional operating temperatures of 650–800 °C.^23,29In this context, small few-nm size ZnO NPs can be expected to be particularly promising, but it is important to understand the manner in which these NPs undergo sulfidation. The structural mechanism of the sulfidation process³⁰ may have critical differences compared to bulk ZnO powders or even larger NPs of tens of nm in size²⁴ and may therefore influence sorbent design. In a seminal study, Park et al.³⁰ studied the sulfidation of hexagonal-shaped 14 nm ZnO nanocrystals (NCs) at high temperature (235 °C) using hexamethyldisilathiane. The reaction was found to involve the anion exchange of O²⁻ with S²⁻ in the NC lattice. The overall shape and crystallography of ZnS NCs was templated by the initial ZnO NCs. However, due to the faster outward diffusion of Zn²⁺ as compared to the inward diffusion of S²⁻, the exchange reaction was accompanied by a nanoscale Kirkendall phenomenon, as a result of which the ZnS NCs formed were hollow.Here, we track the step-wise sulfidation of smaller (ca. 5 nm) ZnO NPs using optical spectroscopy and X-ray crystallography. Prior to the onset of sulfidation, O²⁻ in wurtzite ZnO NPs undergoes substitutional doping with S²⁻ without any major change in its structure. Upon reaching a critical concentration of sulfur doping, separate zincblende ZnS grains form and grow into ZnS NPs. Thus, the sulfidation of these small ZnO NPs studied here is not simply a topotactic or templated place-exchange of anions; rather the nucleation and growth of a separate ZnS crystallite is involved in the latter stages.     

Nickel(ii)-catalyzed tandem C(sp2)–H bond activation and annulation of arenes with gem-dibromoalkenes

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold. Attractive features of this system include its low cost, ease of operation, and its ability to access a wide range of isoindolinones.

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold.

Over the past years, the transition-metal-catalyzed oxidative C–H/C–H cross-coupling reaction has emerged as a useful, atom- and step-economic synthetic protocol to construct a series of important N-heterocycles.¹ In this context, the synthesis of isoindolinones has attracted considerable attention owing to their interesting biological and pharmaceutical properties,² as well as their usefulness as precursors for the synthesis of structurally diverse and complex molecules (Scheme 1).^2c,3 Several methods have successfully been developed toward isoindolinone synthesis based on Pd,⁴ Cu,⁵ Ru,⁶ and Rh⁷ salts. Among these reactions, the oxidative coupling reactions of benzamides with alkenes^4b,6,7a,f,g or alkynes^5a,5d exhibit high atom economy and the application of this strategy to simple arenes is still largely underdeveloped.⁸ For instance, in 2015, Zhang''s group⁹ revealed cobalt-catalyzed oxidative alkynylation and cyclization of simple arenes and terminal alkynes with silver-cocatalyst via 2-fold C–H bond and N–H bond cleavage and C–C bond and C–N bond formation. In 2016, Song''s group¹⁰ developed a method of a cobalt(ii)-catalyzed decarboxylative C–H activation/annulation of benzamides and alkynyl carboxylic acids and nickel(ii)-catalyzed C(sp²)–H alkynylation/annulation cascade with terminal alkynes to synthesize 3-methyleneiso-indolin-1-ones. Zhang also reported a nickel-catalyzed oxidative alkynylation with amides and terminal acetylenes.^10c In addition, from an environmentally point of view, in 2015, wei''s group¹¹ described an operationally simple, Pd-catalyzed C–H functionalization for the synthesis of important and useful isoindolinones from readily available carboxamides and carboxylic acids or anhydrides. The protocol avoided the use of excess oxidants including benzoquinone, Cu(OAc)₂, or Ag₂CO₃ of previous all the reactions, thus generating stoichiometric amounts of undesired wastes.Open in a separate windowScheme 1Representative isoindolinones with biological and pharmaceutical.To our knowledge, the synthesis of alkynes is among the most fundamental and important synthetic transformations due to the unique reactivity of alkynes including addition, oxidation, reduction, and in particular cyclization.¹² However, the lack of reactivity of alkynes, more electron-deficient than the corresponding alkenes, makes it harder to couple them with heteroarenes. As a consequence, terminal alkyne precursors have been developed to facilitate acetylene exchange.¹³ Halogenoalkynes,¹⁴ hypervalent alkynyliodoniums,¹⁵acetylenic sulfones,¹⁶ copper acetylides¹⁷ and α,β-ynoic acids¹⁸ allowed the generation of more activated alkyne moieties thus broadening the applications of direct alkynylation reactions to heterocycles. Among these alternatives, gem-dihaloalkenes emerged as more efficient coupling partners than the corresponding monohalogenated alkynes along with being inexpensive and readily-available.¹⁹ Indeed, the two geminal halogen atoms on the alkenyl carbon enhance the reactivity of metal complexes thus facilitating cross coupling reactions.²⁰ Stable and readily-available 1,1-dibromo-1-alkenes and our interests in the C–H activation²¹ led us to consider using these reagents in the C–H functionalization to construct the valuable isoindolinones. We can envision that the abundance and structural diversity of the aldehydes (used the preparation of gem-dibromoethylenes via wittig reaction) as well as the merits of C–H functionalization would make the synthetic methods desirable and attractive. Herein, we wish to disclose the nickel(ii)/silver(i)-mediated tandem transformation involving sequential C(sp²)–H/C(sp²)–H alkynylation and intramolecular annulation of unactivated arenes with dibromoethylenes with the assistance of 8-aminoquinoline (Scheme 2). These features of this approach operational simplicity, a wide-ranging substrate scope, and tolerance of various synthetically useful functional groups.Open in a separate windowScheme 2Nickel(ii)/silver(i)-catalyzed alkynylation/annulation of arenes with dibromoalkenes.