The GaCl3-Catalyzed Knoevenagel Condensation To Achieve Acceptor-Donor-Acceptor Small-Molecule Acceptors: A DFT Mechanistic Study.

Herein, the reaction mechanism for the GaCl3-catalyzed Knoevenagel condensation of 2-formylindacenodithieno[3,2-b]thiophene (ITIC-CHO) and active methylene compound 1,1-dicyanomethylene-3-indanone (IC) to synthesize ITIC in the presence of acetic anhydride was investigated using the density functional theory (DFT) method. The calculated results indicate that this reaction follows a bimolecular GaCl3 catalytic mechanism. The free energy span for the monomolecular GaCl3 catalytic mechanism is the highest (31.8 kcal/mol), followed by the trimolecular GaCl3 catalytic mechanism (26.4 kcal/mol) and the bimolecular GaCl3 catalytic mechanism (26.3 kcal/mol). The trimolecular GaCl3 path and bimolecular GaCl3 path are competitive, but the former path is limited by the concentration of GaCl3. The inclusion of GaCl3 could stabilize the transition states of C-H activation. Compared to the GaCl3-catalyzed Knoevenagel condensation, that catalyzed by pyridine is not advantageous, owning a high energy span of 31.7 kcal/mol. These agree well with experimental results. This work could provide a novel theoretical understanding of the Knoevenagel condensation, which could inspire the development of a synthesis strategy for electron acceptor materials.

Mapping the awareness and knowledge about patient and public versions of guidelines among stakeholders in China: a cross-sectional survey.

OBJECTIVES: Patient and public versions of guidelines (PVGs) have gradually gained wide recognition and attention from the public and the society due to their scientific, professional, and authoritative characteristics. This study aims to survey the awareness and knowledge of PVGs among stakeholders in China. STUDY DESIGN AND SETTING: This was a cross-sectional survey among stakeholders (guideline developers, clinicians, journal editors, patients, and the public) in China. We self-designed the questionnaire and distributed it through the Questionnaire Star platform. The primary outcomes were awareness of PVGs and opinions about the development methodology, writing, dissemination, and implementation of PVGs. The Kruskal-Wallis H test and post hoc multiple comparison tests were used to compare the levels of awareness of PVGs between different subgroups of respondents. RESULTS: A total of 1319 valid questionnaires were collected: 722 from guideline developers, 136 from clinicians, 83 from journal editors, 284 from patients, and 94 from members of the public. Of all respondents, 253 (19.2%) had not heard of PVGs, 349 (26.5%) had heard of PVGs but had no further knowledge, 475 (36.0%) had some knowledge of PVGs, and 242 (18.3%) were familiar with or had participated in the development of PVGs. Guideline developers, clinicians, and journal editors had higher awareness than patients and the public. Higher education and older age also correlated with higher awareness of PVGs. More than half (52.9%) of guideline developers considered that both rewriting of the source guidelines and direct development as independent documents were appropriate methods for developing PVGs. The survey respondents agreed that clinicians (97.3%), guideline methodologists (76.6%), representatives of patients and the public (74.5%), and medical editors or writers (63.4%) should participate in the development of PVGs. More than 80% of the respondents agreed that the quality of evidence and strength of recommendations should be presented; however, there was no consensus in the form of presentation. CONCLUSIONS: The level of awareness of PVGs among stakeholders in China is relatively low and differs between different stakeholder groups, but the majority of key stakeholders have a positive attitude toward PVGs. The collection of the perspectives and opinions on the development methods, writing, dissemination, and implementation provides a key reference and basis for the future optimization and improvement of PVGs development.

Theoretical study on hydroformylation catalyzed by cationic cobalt(II) complexes.

Hydroformylation is one of the most important homogeneous reactions in industrial production. Herein, a density functional theory (DFT) method was employed to investigate two proposed reaction mechanisms of hydroformylation catalyzed by cationic cobalt(II) complexes, the carbonyl dissociative mechanism and the associative mechanism. The calculated results showed that the heterolytic H2 activation is the rate-determining step for both the dissociative mechanism and the associative mechanism, with energy barriers of 26.8 kcal mol-1 and 40.5 kcal mol-1, respectively. Meanwhile, the regioselectivity, the spin multiplicity of the catalyst and the substituent effects on the reaction were also investigated. The most stable cobalt(II) catalyst has a doublet state and the linear aldehyde is the dominant product. In addition, it was found that the energy barrier of the reaction decreased when the electron density of the Co center of the catalyst was increased by changing the ligand. The catalytic activity of the catalyst was proposed to be the best when the PEt2 group of the ligand is replaced by the P(tBu)2 group. This study might not only provide new insights for hydroformylation catalyzed by cobalt but also facilitate theory-guided design of novel transition metal catalysts for hydroformylation.

Molecular Modulators and Receptors of Selective Autophagy: Disease Implication and Identification Strategies.

Autophagy is a highly conserved physiological process that maintains cellular homeostasis by recycling cellular contents. Selective autophagy is based on the specificity of cargo recognition and has been implicated in various human diseases, including neurodegenerative diseases and cancer. Selective autophagy receptors and modulators play key roles in this process. Identifying these receptors and modulators and their roles is critical for understanding the machinery and physiological function of selective autophagy and providing therapeutic value for diseases. Using modern researching tools and novel screening technologies, an increasing number of selective autophagy receptors and modulators have been identified. A variety of Strategies and approaches, including protein-protein interactions (PPIs)-based identification and genome-wide screening, have been used to identify selective autophagy receptors and modulators. Understanding the strengths and challenges of these approaches not only promotes the discovery of even more such receptors and modulators but also provides a useful reference for the identification of regulatory proteins or genes involved in other cellular mechanisms. In this review, we summarize the functions, disease association, and identification strategies of selective autophagy receptors and modulators.

2D/3D Perovskite Photodetectors with High Response Frequency and Improved Stability Based on Thiophene-2-ethylamine and Dual Additives.

Organic-inorganic lead halide perovskite materials have received great attention in recent years. However, the poor stability of these materials severely limits the commercial application of perovskite devices. Here, we used thiophene-2-ethylammonium iodide (TEAI) material as the organic spacer NH4SCN and NH4Cl as the dual additives to realize high-stability two-dimensional (2D)/three-dimensional (3D) perovskite thin films for perovskite photodetectors. Then, we investigated different effects of the dual additives on the orientation and crystallinity of the perovskite films. At room temperature, the optimized 2D/3D perovskite photodetectors exhibit good performance with high external quantum efficiency (EQE) (72%), large responsivity (0.36 A/W), high detectivity (2.46 × 1012 Jones at the bias of 0 V), high response frequency (1.7 MHz), and improved stability (retains 90% photocurrent after 2000 h storage in RT and 10% RH conditions). Based on these devices, a dual-channel optical transport system and a light-intensity adder are achieved. The results of this study indicate that, with a simple process, the TEAI and dual-additives based 2D/3D perovskite photodetectors have promising applications in light-intensity adder and optical communication systems.

Mechanistic insights into amide formation from aryl epoxides and amines catalyzed by ruthenium pincer complexes: a DFT study.

The synthesis of amides is of great significance in academia and industrial fields. Herein, density functional theory (DFT) studies were employed to investigate the mechanism of the formation of amides via aryl epoxides and amines catalyzed by ruthenium pincer complexes. The entire reaction mainly comprises three processes: isomerization of epoxides to aldehydes, aldimine condensation, and amide formation. Calculated results showed that bipyridine-based Ru-PNN A1 (PNN = 2-(di-tert-butylphosphinomethyl)bipyridine) pincer complexes could be potential highly catalytic species for the synthesis of amides and that the rate-determining step is the amine-assisted hydrogen elimination with a free energy barrier of 28.0 kcal mol-1. This study might not only provide new insights into the future of the formation of amides by transition-metal complexes but also facilitate the theoretical guidance needed to design novel transition-metal catalysts.

Understanding the Mechanism and Selectivity of 1,1-Diborylalkanes from Alkenes Catalyzed by a Zirconium Complex.

The synthesis of 1,1-diborylalkanes from readily available alkenes is an appealing method. The density functional theory (DFT) method was employed to investigate the reaction mechanism of 1,1-diborylalkanes, which was synthesized from alkenes and a borane, and the reaction was catalyzed by a zirconium complex Cp2ZrCl2. The entire reaction is divided into two cycles: dehydrogenative boration to form vinyl boronate esters (VBEs) and hydroboration of VBEs. This article focuses on the hydroboration cycle and elaborates on the role of the reducing reagents in the equilibrium of self-contradictory reactivity (dehydrogenative boration and hydroboration). The H2 and HBpin pathways were investigated as the reducing reagents in the hydroboration process. The calculated results showed that it is more advantageous to use H2 as a reducing agent (path A). Furthermore, the σ-bond metathesis is the rate-determining step (RDS) with an energetic span of 21.4 kcal/mol. This is consistent with the self-contradictory reactivity balance proposed in the experiment. The reaction modes of the hydroboration process were also discussed. These analyses revealed the origin of selectivity in this boration reaction, in which the σ-bond metathesis of HBpin needs to overcome the strong interaction between HBpin and the Zr metal. Meanwhile, the origin of the selectivity of different positions of H2 is the interaction between the σ(H1-H2) → σ*(Zr1-C1) overlap and these findings have implications for catalyst design and application.

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines.

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C6 F5 )2 allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH3 to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C6 F5 )2 and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.

Theoretical Study on Photothermal Properties of Azobenzene Sulfonate/Magnesium-Aluminum Hydroxide Composite Dye.

The assembly of various azo dyes and pigments with inorganic layered materials could develop new types of intercalation materials. The electronic structures and photothermal properties of composite materials (AbS--LDH) constituted by azobenzene sulfonate anions (AbS-) and Mg-Al layered double hydroxide (LDH) lamella were theoretically studied at the M06-2X/def2-TZVP//M06-2X/6-31G(d,p) level using density functional theory and time-dependent density functional theory. Meanwhile, the influences of LDH lamella on the AbS- in AbS--LDH materials were investigated. The calculated results showed that the addition of LDH lamella could lower the isomerization energy barrier of CAbS- anions (CAbS- stands for cis AbS-). The thermal isomerization mechanisms of AbS--LDH and AbS were related to the conformational change of the azo group, out-of-plane rotation and in-plane inversion. The LDH lamella could reduce the energy gap of the n → π* and π → π* electronic transition and lead to a red-shift in the absorption spectra. When a polar solvent DMSO was applied, the excitation energy of the AbS--LDHs was increased, making its photostability stronger than in nonpolar solvent and solvent-free.

DFT Mechanistic Investigation on Manganese Pincer Complex Catalysed Cross-Coupling of Methanol with Benzyl Alcohol to Afford Methyl Benzoate.

In this paper the density functional theory (DFT) method was employed to investigate the cross-coupling of methanol with benzyl alcohol to afford methyl benzoate, catalysed by Mn-PNN pincer complex. The whole reaction process mainly includes three stages: the dehydrogenation of benzyl alcohol to benzaldehyde, the coupling of benzaldehyde with methanol to hemiacetal and the dehydrogenation of hemiacetal to methyl benzoate. The calculated results indicated that two dehydrogenation processes are influenced by two competitive mechanisms of inner and outer spheres. Dehydrogenation of benzyl alcohol to benzaldehyde is the rate-determining step of the whole reaction, with the energy barrier of 22.1 kcal/mol. In addition, the regeneration of catalyst is also extremely important. Compared with direct dehydrogenation, the dehydrogenation mode assisted by formic acid is more advantageous. This work might provide theoretical insights and shed light on the design of cheap transition-metal catalysts for the dehydrogenation reaction.

The Origin of Stereoselectivity in the Hydrogenation of Oximes Catalyzed by Iridium Complexes: A DFT Mechanistic Study.

Herein the reaction mechanism and the origin of stereoselectivity of asymmetric hydrogenation of oximes to hydroxylamines catalyzed by the cyclometalated iridium (III) complexes with chiral substituted single cyclopentadienyl ligands (Ir catalysts A1 and B1) under acidic condition were unveiled using DFT calculations. The catalytic cycle for this reaction consists of the dihydrogen activation step and the hydride transfer step. The calculated results indicate that the hydride transfer step is the chirality-determining step and the involvement of methanesulfonate anion (MsO-) in this reaction is of importance in the asymmetric hydrogenation of oximes catalyzed by A1 and B1. The calculated energy barriers for the hydride transfer steps without an MsO- anion are higher than those with an MsO- anion. The differences in Gibbs free energies between TSA5-1fR/TSA5-1fS and TSB5-1fR/TSB5-1fS are 13.8/13.2 (ΔΔG‡ = 0.6 kcal/mol) and 7.5/5.6 (ΔΔG‡ = 1.9 kcal/mol) kcal/mol for the hydride transfer step of substrate protonated oximes with E configuration (E-2a-H+) with MsO- anion to chiral hydroxylamines product R-3a/S-3a catalyzed by A1 and B1, respectively. According to the Curtin-Hammet principle, the major products are hydroxylamines S-3a for the reaction catalyzed by A1 and B1, which agrees well with the experimental results. This is due to the non-covalent interactions among the protonated substrate, MsO- anion and catalytic species. The hydrogen bond could not only stabilize the catalytic species, but also change the preference of stereoselectivity of this reaction.

Density Functional Theory Study on the H2-Acceptorless Dehydrogenative Boration of Alkenes Catalyzed by a Zirconium Complex.

For the synthesis of vinyl boronate esters, the direct catalytic H2-acceptorless dehydrogenative boration of alkenes is one of the promising strategies. In this paper, the density functional theory method was employed to investigate the reaction mechanism of dehydrogenative boration and transfer boration of alkenes catalyzed by a zirconium complex (Cp2ZrH2). There are two possible pathways for this reaction: the alkene insertion followed by the dehydrogenative boration (path A) and the alkene insertion after the dehydrogenative boration (path B). The calculated results showed that path A is more favorable than path B, and that the rate-determining step is the C-B coupling step with an energy barrier of 18.7 kcal/mol. The reaction modes of the C-B coupling assisted dehydrogenative boration and the alkene insertion were also discussed. These analyses reveal a novel hydrogen release behavior in dehydrogenative boration and the alkene insertion modes and sequences were proposed to be of importance in the chemoselectivity of this reaction. In addition, the X ligand effect (X = H, Cl) on the catalytic activity of the zirconium complex was explored, indicating that the H ligand could enhance the catalytic activity of the complex for styrene dehydrogenative boration.

Palladium-catalyzed oxidative Heck reaction of non-activated alkenes directed by fluorinated alcohol.

A novel, Pd-catalyzed oxidative Heck reaction of non-activated alkenes synergistically directed by bifunctional groups has been developed firstly by using O2 as a green oxidant, yielding the oxidative Heck products with excellent yields in a regio- and stereoselective manner. This bifunctional synergistic activation mechanism was demonstrated by experimental analysis and detailed computational studies, wherein the hydroxyl group directs the migratory insertion of the alkenes and the trifluoromethyl group facilitates the subsequent ß-H elimination and reductive elimination. Moreover, a pesticidal active compound was synthesized using the bifunctional synergistically directed C-H arylation as the key step, which demonstrated its synthetic utility.

Hydride Relay Exchange Mechanism for the Heterocyclic C-H Arylation of Benzofuran and Benzothiophene Catalyzed by Pd Complexes.

The mechanism and regioselectivity of the heterocyclic C-H arylation of benzofuran and benzothiophene catalyzed by Pd(OAc)2 complexes were investigated using the density functional theory (DFT) method. The Pd(0)L2(PhI) complex (L = HOAc) is proposed to be the catalytic species. Compared to the traditional Heck-type mechanism, concerted metalation-deprotonation (CMD) mechanism, and electrophilic aromatic substitution (SEAr) mechanism for the C-H arylation, a new hydride relay exchange mechanism was proposed for the benzoheterocyclic C-H arylation catalyzed by Pd complexes, which consists of two redox processes between Pd(II) and Pd(0) species to complete the regioselective C-H activation. The calculated results indicate that the reaction along the hydride relay exchange mechanism is more favorable than those along other mechanisms, including the traditional Heck-type mechanism and the base-assisted anti-H elimination mechanism. This agrees well with the experimental results. Meanwhile, the origin for the regioselective C-H arylation was unveiled in which the α-C-H arylation products are major for the heterocyclic C-H arylation of benzofuran, but the ß-C-H arylation products are major for that of benzothiophene. This study might provide a deep mechanistic understanding on the regioselective C-H activation and arylation of benzoheterocycle compounds catalyzed by transition-metal complexes.

Transition-Metal-Free Synthesis of Functionalized Quinolines by Direct Conversion of ß-O-4 Model Compounds.

Direct production of heterocyclic aromatic compounds from lignin ß-O-4 models remains a huge challenge due to the incompatible catalysis for aryl ether bonds cleavage and heterocyclic ring formation. Herein, the first example of quinoline synthesis from ß-O-4 model compounds by a one-pot cascade reaction is reported in yields up to 89 %. The reaction pathway involves selective cleavage of C-O bonds, dehydrogenation, aldol condensation, C-N bond formation along with heterocyclic aromatic ring construction. The control experiments suggest that both imine and chalcone were identified as the key intermediates, and the rate determining step as well as the preferred pathway were experimentally clarified and supported by density functional theory (DFT) calculations. Based on this protocol, the conversion of ß-O-4 polymer delivered 56 wt % yield of quinoline derivative in three steps. This transformation provides a potential petroleum-independent choice for heterocyclic aromatic chemicals.

Transition-metal-free synthesis of pyrimidines from lignin ß-O-4 segments via a one-pot multi-component reaction.

Heteroatom-participated lignin depolymerization for heterocyclic aromatic compounds production is of great importance to expanding the product portfolio and meeting value-added biorefinery demand, but it is also particularly challenging. In this work, the synthesis of pyrimidines from lignin ß-O-4 model compounds, the most abundant segment in lignin, mediated by NaOH through a one-pot multi-component cascade reaction is reported. Mechanism study suggests that the transformation starts by NaOH-induced deprotonation of Cα-H bond in ß-O-4 model compounds, and involves highly coupled sequential cleavage of C-O bonds, alcohol dehydrogenation, aldol condensation, and dehydrogenative aromatization. This strategy features transition-metal free catalysis, a sustainable universal approach, no need of external oxidant/reductant, and an efficient one-pot process, thus providing an unprecedented opportunity for N-containing aromatic heterocyclic compounds synthesis from biorenewable feedstock. With this protocol, an important marine alkaloid meridianin derivative can be synthesized, emphasizing the application feasibility in pharmaceutical synthesis.

MAPbI3 Photodetectors with 4.7 MHz Bandwidth and Their Application in Organic Optocouplers.

The photodetector based on methylammonium lead iodide (MAPbI3) is a promising device for wide wavelength range (380-780 nm) sensitivity. However, its industrial application is limited by the relatively low response speed to the light signal, which has received little attention. Only a few reports show low-bandwidth characteristics (less than 1 MHz at 0.1 cm2). Here, when a cosolvent strategy to manipulate the thickness and the crystallinity of the MAPbI3 film is adopted, photodetectors with a -3 dB bandwidth of 4.7 MHz are achieved (at 0.16 cm2 photo detecting area). The performance is significantly better than most of the organic and hybrid photodetectors reported so far. Based on this photodetector and an organic light-emitting diode (OLED), an organic optocoupler system with 1 MHz response frequency is successfully set up. Our results suggest that thickness-manipulated cosolvent strategy is a promising method in high-speed MAPbI3-based photodetectors.

The Role of AQ in the Regioselectivity of Strong Alkyl C-O Bond Activation Catalyzed by Pd(OAc)2: A Density Functional Theory Mechanistic Study.

A density functional theory method was employed to investigate the mechanism of C-O bond activation of butanoic acid substrates bearing the 8-aminoquinoline (AQ) group catalyzed by Pd(OAc)2. The whole reaction consists of five fundamental steps: the chelation of substrate A1, the C-H activation step, the C-N coupling step, the protodepalladation step, and the release of the final product. The calculated results indicated that the protodepalladation step is the rate-determining step with a free energy barrier of 24.3 kcal/mol. This theoretical study pointed out that the energy barriers of C-H activation in the presence and absence of AQ are 11.3 and 26.6 kcal/mol, respectively. This is to say that the installation of the AQ directing group is critical to the regioselectivity of C-H activation and the ß-O elimination steps, and this reason enables selective activation of the γ C-O bond. Furthermore, this chelating functionality facilitated the protodepalladation step because the energy barrier of the protodepalladation step was decreased with the coordination of the AQ directing group with a Pd center, and that was 39.3 kcal/mol in the absence of AQ. This also explains why no product formation was observed in the experiment upon changing the directing AQ group to a phenylamino group. Finally, other substrates bearing the phenol leaving group at the ß- and δ-positions of carbonyl were investigated in order to expand the applicability of the AQ directing strategy. This work could provide new theoretical insights into the activation of strong alkyl C(sp3) covalent bonds via the AQ directing strategy.

Therapeutic Applications of Functional Nanomaterials for Prostatitis.

Prostatitis is a common disease in adult males, with characteristics of a poor treatment response and easy recurrence, which seriously affects the patient's quality of life. The prostate is located deep in the pelvic cavity, and thus a traditional infusion or other treatment methods are unable to easily act directly on the prostate, leading to poor therapeutic effects. Therefore, the development of new diagnostic and treatment strategies has become a research hotspot in the field of prostatitis treatment. In recent years, nanomaterials have been widely used in the diagnosis and treatment of various infectious diseases. Nanotechnology is a promising tool for 1) the accurate diagnosis of diseases; 2) improving the targeting of drug delivery systems; 3) intelligent, controlled drug release; and 4) multimode collaborative treatment, which is expected to be applied in the diagnosis and treatment of prostatitis. Nanotechnology is attracting attention in the diagnosis, prevention and treatment of prostatitis. However, as a new research area, systematic reviews on the application of nanomaterials in the diagnosis and treatment of prostatitis are still lacking. In this mini-review, we will highlight the treatment approaches for and challenges associated with prostatitis and describe the advantages of functional nanoparticles in improving treatment effectiveness and overcoming side effects.

Asymmetric Induction with a Chiral Amine Catalyzed by a Ru-PNP Pincer Complex: Insight from Theoretical Investigation.

In this paper, the mechanism of asymmetric amination of a racemic alcohol with Ellman's sulfinamide and the origin of diastereoselectivity catalyzed by a Ru-PNP pincer complex were studied using density functional theory (DFT). The mechanism involves dehydrogenation of the racemic alcohol, C-N coupling, and hydrogen transfer from the catalyst to the in situ formed imine. The calculated results indicate that both the alcohol dehydrogenation and imine hydrogenation are stepwise. The hydride transfer from a Ru hydride complex to the imine is shown to be the chirality-determining step in the whole catalytic cycle. It was found that the diastereoselectivity mainly stems from the hydrogen bonding interactions between the oxygen atom of the sulfinyl moiety and the hydrogen atom of the NH group of the ligand.