Large-Scale Synthesis of High-Loading Single Metallic Atom Catalysts by a Metal Coordination Route.

Single atom catalyst (SAC) is one of the most efficient and versatile catalysts with well-defined active sites. However, its facile and large-scale preparation, the prerequisite of industrial applications, has been very challenging. This dilemma originates from the Gibbs-Thomson effect, which renders it rather difficult to achieve high single atom loading (< 3 mol%). Further, most synthesizing procedures are quite complex, resulting in significant mass loss and thus low yields. Herein, a novel metal coordination route is developed to address these issues simultaneously, which is realized owing to the rapid complexation between ligands (e.g., biuret) and metal ions in aqueous solutions and subsequent in situ polymerization of the formed complexes to yield SACs. The whole preparation process involves only one heating step operated in air without any special protecting atmospheres, showing general applicability for diverse transition metals. Take Cu SAC for an example, a record yield of up to 3.565 kg in one pot and an ultrahigh metal loading 16.03 mol% on carbon nitride (Cu/CN) are approached. The as-prepared SACs are demonstrated to possess high activity, outstanding selectivity, and robust cyclicity for CO2 photoreduction to HCOOH. This research explores a robust route toward cost-effective, massive production of SACs for potential industrial applications.

Simultaneous Passivation of Perovskite Interfaces at Multiple Active Sites Improves Device Performance: Combining Theory and Experiment.

A multisite interface passivation material named 2-mercapto-4-methyl-5-thiazoleacetic acid (MMTA) is used to optimize the perovskite film top interface. DFT calculations and experiments show that MMTA can effectively passivate interface defects. Finally, the champion device's photoelectric conversion efficiency reached 23.44%, which possessed long-term stability.

Investigation of Temperature-Dependent Phonon Anharmonicity and Thermal Transport in SnS Single Crystals.

Tin sulfide has outstanding thermoelectric properties in the b-axis direction of crystallography as a IV-VI group layered compound, which arouses great attention. In this study, temperature-dependent Raman spectroscopy (TDRS) is used to quantify the phonon anharmonicity in SnS crystals from 77 to 475 K, where the three-phonon process dominates in this temperature region. Moreover, integration of the four-phonon process and lattice thermal expansion will better describe the temperature-dependent Raman experimental phenomenon. The good agreement between the calculated and experimental lattice thermal conductivity confirms the three-phonon scattering process is the dominant scattering mechanism at this temperature range. Further, combining the atomic thermal displacement and charge density through density functional theory calculation, the inherently low thermal conductivity of SnS is because of strong lattice anharmonicity, which is brought by the presence of asymmetric chemical bonding resulting from the Sn 5s2 lone pair electrons. These results provide key insights for studying thermal properties of other low-dimensional materials.

Functionalized polymer modified buried interface for enhanced efficiency and stability of perovskite solar cells.

Although great progress has been made in perovskite solar cells (PCSs), further development of PCSs is hindered by a large number of defects, nonradiative recombination, and mysterious stresses. Here, we propose a new interfacial strategy by introducing a new polymer material named povidone-iodine (PV-I) as a buffer layer. A series of studies indicate that the introduced buffer layer can form a strong chemical interaction with SnO2 and the perovskite, which can not only passivate the defects of the two functional layers but also strengthen the interfacial connection. The reduction of film defects and the enhancement of interface connection are beneficial to the extraction and transport of the carrier. In addition, the introduction of a buffer layer releases the interfacial stress. Ultimately, we achieved attractive efficiency (22.02%, 0.1 cm2) and considerable long-term stability (after aging 500 h, the target device still retains 81% of its original PCE). The excellent performance of the device indicates that this strategy can be used as an effective control method for perovskite solar cells to facilitate their commercialization.

Multistrategy Preparation of Efficient and Stable Environment-Friendly Lead-Based Perovskite Solar Cells.

Perovskite solar cells (PSCs) have achieved huge success in power conversion efficiency (PCE) and stability. However, further improving the PCE of PSCs and stability is still a big challenge. Here, we attempt to improve the PCE and stability of PSCs using a functional additive named 3-mercaptopropyltriethoxysilane (SiSH) in the perovskite antisolvent. It is revealed that SiSH can release the stress in the film, reduce the defects, and inhibit lithium-ion migration and lead leakage. As a result, the target device achieves an efficiency enhancement from 20.80 to 22.42% as compared to the control device. Meanwhile, device stability is ameliorated after SiSH modification. Furthermore, new adsorbents are used to treat the leaked lead to make it comply with safe drinking water standards. This work provides an idea for developing multifunctional antisolvent additives and adsorbents for high PCE, long stability, and environment-friendly Pb-based PSCs.

In-situ micro-Raman study of SnSe single crystals under atmosphere: Effect of laser power and temperature.

Single crystal of tin selenide (SnSe) was studied by micro-Raman spectroscopy under atmosphere conditions. The effect of varying the incident laser power on the sample up to 2 mW was analyzed. The Raman spectra showed that the number of all vibrational modes have not decreased or increased, but all peaks red-shifted and softened obviously as the laser power increased to the threshold value. The temperature-dependent micro-Raman study of the single crystal was carried out for illustrating thermal effect due to the high incident laser power. A new SnSe2 phase appeared at high temperature without vacuum and become the dominant phase at the surface of the crystal gradually because of oxidation. Detecting few amounts of SnSe2 crystals on the surface of single crystal shows the high sensitivity of Raman spectroscopy. High resolution transmission electron microscopy (HRTEM) was also used to confirm that the newly generated SnSe2 phase is precipitated by SnSe under high temperature oxidation conditions. To study the Raman spectra of low thermal conductivity materials under high temperature and non-vacuum conditions, lower incident laser power should be used to avoid the influence of additional thermal effects.

Revealing the anisotropic phonon behaviours of layered SnS by angle/temperature-dependent Raman spectroscopy.

Tin sulfide (SnS), a IV-VI group layered compound, has attracted much attention because of its excellent thermoelectric properties along the crystallographic b-axis. However, there are few reports on the identification of its in-plane orientation. We observe a strong anisotropy of the in-plane Raman signal in bulk SnS. With the help of ab initio calculations, the vibrational symmetry of each observed Raman mode in the cleaved (00l)-plane is consistent with the experimental values. The angle-resolved polarized Raman spectroscopy, combined with electron backscattered diffraction technology, is utilized to systematically investigate the in-plane anisotropy of the phonon response and then determine the in-plane orientation. Furthermore, the temperature-dependent and laser-power-dependent Raman scattering analyses reveal that the adjacent layers in the SnS crystals show a relatively weak van der Waals interaction. These findings could provide much-needed experimental information for future applications related to the anisotropic transport properties of SnS single crystals.

Constructing highly active Co sites in Prussian blue analogues for boosting electrocatalytic water oxidation.

High-valence cobalt sites are considered as highly active centers for the oxygen evolution reaction (OER) and their corresponding construction is thus of primary importance in the pursuit of outstanding performance. Herein, we report the design and facile synthesis of abundant high-valence cobalt sites by introducing Zn2+ into CoFe Prussian blue analogues (PBAs). The modification results in the drastic morphological transformation from a pure phase (CoFe-PBA) to a three-phase composite (CoFeZn-PBA), with a significant increase not only the amount of highly oxidized Co sites but the specific surface area (by up to 4 times). Moreover, the obtained sample also exhibits outstanding electric conductivity. Consequently, an excellent OER performance with an overpotential of 343 mV@10 mA cm-2 and a Tafel slope of 75 mV dec-1 was achieved in CoFeZn-PBA, which outperforms the commercial IrO2 catalyst. Further analysis reveals that CoFeZn-PBA becomes (oxyhydr)oxides after the OER.

Read-across: Principle, case study and its potential regulatory application in China.

Read-across, has generated much attention and has been used in many regulatory schemes as an alternative approach to testing globally. The regulatory application of read-across in the chemical management in China is progressing but still limited. A workshop on the "Read-across: Principle, case study and its potential regulatory application in China", organized by the Chemical Risk Assessment Specialty Group under the Committee of Industrial Toxicology of Chinese Society of Toxicology, was held on May 28, 2019 to discuss the potential broader application and acceptance of read-across to support chemical risk assessment in China. The Workshop included global experts from regulatory agencies, academia and industry. Scientific presentations and constructive discussions raised awareness on the use of read-across in different regions, identified barriers to regulatory acceptance, and participants also brainstormed on practical strategies to help facilitate the further regulatory application of read-across approaches in China.

Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes.

PPARgamma and 11beta-HSD1 are attractive therapeutic targets for type 2 diabetes. However, PPARgamma agonists induce adipogenesis, which causes the side effect of weight gain, whereas 11beta-HSD1 inhibitors prevent adipogenesis and may be beneficial for the treatment of obesity in diabetic patients. For the first time, we designed, synthesized a series of alpha-aryloxy-alpha-methylhydrocinnamic acids as dual functional agents which activate PPARgamma and inhibit 11beta-HSD1 simultaneously. The compound 11e exhibited the most potent inhibitory activity compared to that of the lead compound 2, with PPARgamma (EC(50)=6.76 microM) and 11beta-HSD1 (IC(50)=0.76 microM) in vitro. Molecular modeling study for compound 11e was also presented. Compound 11e showed excellent efficacy for lowering glucose, triglycerides, body fat, in well established mice and rats models of diabetes and obesity and had a favorable ADME profile.

Dynamic mechanism of fatty acid transport across cellular membranes through FadL: molecular dynamics simulations.

FadL is an important member of the family of fatty acid transport proteins within membranes. In this study, 11 conventional molecular dynamics (CMD) and 25 steered molecular dynamics (SMD) simulations were performed to investigate the dynamic mechanism of transport of long-chain fatty acids (LCFAs) across FadL. The CMD simulations addressed the intrinsically dynamic behavior of FadL. Both the CMD and SMD simulations revealed that a fatty acid molecule can move diffusively to a high-affinity site (HAS) from a low-affinity site (LAS). During this process, the swing motion of the L3 segment and the hydrophobic interaction between the fatty acid and FadL could play important roles. Furthermore, 22 of the SMD simulations revealed that fatty acids can pass through the gap between the hatch domain and the transmembrane domain (TMD) by different pathways. SMD simulations identified nine possible pathways for dodecanoic acid (DA) threading the barrel of FadL. The binding free energy profiles between DA and FadL along the MD trajectories indicate that all of the possible pathways are energetically favorable for the transport of fatty acids; however, one pathway (path VI) might be the most probable pathway for DA transport. The reasonability and reliability of this study were further demonstrated by correlating the MD simulation results with the available mutagenesis results. On the basis of the simulations, a mechanism for the full-length transport process of DA from the extracellular side to the periplasmic space mediated by FadL is proposed.

Structure-based drug design of a novel family of chalcones as PPARalpha agonists: virtual screening, synthesis, and biological activities in vitro.

AIM: To design and synthesize a novel class of peroxisome proliferator-activated receptors (PPAR)alpha agonists, which is obtained by the combination of the classical fibrate "head group", a linker with appropriate length and a chalcone. METHODS: Thirty seven compounds were designed and identified employing the virtual screening approach. Six compounds were then selected for synthesis and bioassay according to the virtual screening results, structural similarity, and synthetic complexity. RESULTS: Six new compounds (4b and 4d-h) were synthesized and bioassayed. All were found to be potent PPARalpha agonists, compound 4 h being the most prominent with a 50% effective concentration value of 0.06 micromol/L. CONCLUSION: This study provides a promising novel family of chalcones with a potential hypolipidemic effect.

Molecular insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods.

The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method combined with alanine-scanning mutagenesis is a very important tool for rational drug design. In this study, molecular dynamics (MD) and MM-PBSA were applied to calculate the binding free energy between the rat intestinal fatty acid binding protein (IFABP) and palmitic acid (PA) to gain insight to the interaction details. Equally spaced snapshots along the trajectory were chosen to perform the binding free energy calculation, which yields a result highly consistent with experimental value with a deviation of 0.4 kcal/mol. Computational alanine scanning was performed on the same set of snapshots by mutating the residues in IFABP to alanine and recomputing the DeltaDeltaG(binding). By postprocessing a single trajectory of the wild-type complex, the average unsigned error of our calculated DeltaDeltaG(binding) is below 1.5 kcal/mol for most of the alanine mutations of the noncharged residues (67% in total). To further investigate some particular mutants, three additional dynamical simulations of IFABP Arg126Ala, Arg106Ala, and Arg106Gln mutants were conducted. Recalculated binding free energies are well consistent with the experimental data. Moreover, the ambiguous role of Arg106 caused by the free energy change of the opposite sign when it is mutated to alanine and glutamine respectively is clarified both structurally and energetically. Typically, this can be attributed to the partial electrostatic compensation mainly from Arg56 and the obvious entropy gain in Arg106Ala mutant while not in Arg106Gln mutant. The presented structural model of IFABP-PA complex could be used to guide future studies.

Why does beta-secretase zymogen possess catalytic activity? Molecular modeling and molecular dynamics simulation studies.

Beta-secretase is a potential target for inhibitory drugs against Alzheimer's disease as it cleaves amyloid precursor protein (APP) to form insoluble amyloid plaques and vascular deposits in the brain. Beta-secretase is matured from its precursor protein, called beta-secretase zymogen, which, different from most of other zymogens, is also partially active in cleaving APP. Hence, it is important to study on the mechanism of the zymogen's activation process. This study was to model the 3-D structure of the zymogen, followed by intensive molecular dynamics (MD) simulations to identify the most probable 3-D model and to study the dynamic structural behavior of the zymogen for understanding the effects of pro-segment on the function of the enzyme. The results revealed that the dropping in catalytic activity of the beta-secretase zymogen could be attributed to the occupation of the entrance of the catalytic site of the zymogen by its pro-segment. On the other hand, the partial catalytic activity of the zymogen could be explained by high fluctuation of the pro-segment in comparison with that of other zymogens, resulting in the occasionally exposure of the catalytic site for access its substrate APP. Indeed, steered MD (SMD) simulation revealed a weak pulling force at quasi-equilibrium state for the pro-segment of the zymogen leaving from the entrance, indicating that this swinging process could take place spontaneously. Furthermore, MM-PBSA calculation revealed a small change of free energy of 10.56 kal/mol between the initial and final states of the process of pro-segment swung outside the binding pocket of beta-secretase zymogen. These results not only account for the partial catalytic activity of beta-secretase zymogen, but also provide useful clues for discovering new potent ligands, as new type of drug leads for curing Alzheimer's disease, to prevent the pro-segment of the zymogen from leaving its catalytic site.

3D-QSAR study of 20 (S)-camptothecin analogs.

AIM: To build up a quantitative structure-activity relationship (QSAR) model of 20 (S)-camptothecin (CPT) analogs for the prediction of the activity of new CPT analogs for drug design. METHODS: A training set of 43 structurally diverse CPT analogs which were inhibitors of topoisomerase I were used to construct a quantitative structure-activity relationship model with a comparative molecular field analysis (CoMFA). The QSAR model was optimized using partial least squares (PLS) analysis. A test set of 10 compounds was evaluated using the model. RESULTS: The CoMFA model was constructed successfully, and a good cross-validated correlation was obtained in which q(2) was 0.495. Then, the analysis of the non-cross-validated PLS model in which r(2) was 0.935 was built and permitted demonstrations of high predictability for the activities of the 10 CPT analogs in the test set selected in random. CONCLUSION: The CoMFA model indicated that bulky negative-charged group at position 9, 10 and 11 of CPT would increase activity, but excessively increasing bulky group at position 10 is adverse to inhibitory activity; substituents that occupy position 7 with the bulky positive group will enhance the inhibitive activity. The model can be used to design new CPT analogs and understand the mechanism of action.