Active Site Research Articles

Active Sites of Cu/ZnO-Based Catalysts for CO2 Hydrogenation to Methanol: Part I

Heterogeneous Cu/ZnO-based catalysts are widely used for CO2 hydrogenation to methanol, but limitations remain for industrial applications. These include achieving high methanol selectivity and conversion and mitigating deactivation by water poisoning. Part I of this review explores the role of active sites on Cu/ZnO-based catalysts in CO2 conversion. The synergistic interaction between copper and zinc oxide is emphasised, particularly regarding interfacial effects on carbon monoxide activation and formate formation. The discussion covers theoretical and experimental perspectives on active site characteristics, including defects, vacancies, steps and strain. Additionally, the review explores the connection between Cu/ZnO-based catalysts properties and methanol synthesis activity.

Synthesis, and In-silico Studies of Indole-chalcone Derivatives Targeting Estrogen Receptor Alpha (ER-α) for Breast Cancer.

Breast cancer is the prominent reason of death in women worldwide, and the cases are increasing day by day. There are many FDA-approved drugs for treating breast cancer. Due to drug resistance, and problems in selectivity, there is a need to develop more effective agents with few side effects. Indole derivatives have demonstrated significant pharmacological potential as anti-breast cancer agents. Further, chalcone derivatives incorporating heterocyclic scaffolds play a significant role in medicine. Indole-chalcone-based compounds offer the potential for improved biological activity and enhanced drug-like properties. It prompted us to explore the synthesis of Indole-Chalcone derivatives targeting estrogen receptor alpha (ER-α) to discover potent anti-breast cancer agents. To synthesize indole-chalcone derivatives and study their binding interactions for ER-α protein by molecular docking for breast cancer treatment. In this study, indole-chalcone derivatives have been synthesized using conventional heating. With the help of Schrodinger software, molecular interaction as well as ADME (Adsorption, Distribution, Metabolism, and Excretion) studies of the compounds were conducted. Among all the synthesized compounds, four compounds (1, 2, 3, and 4) showed better docking scores (-10.24 kcal/mol, -10.15 kcal/mol, -9.40 kcal/mol, -9.29 kcal/mol, respectively) than the standard tamoxifen (-8.43 kcal/mol). From In-silico studies, we can conclude that four compounds from the synthesized series fit into the active site of ER-α. ADME properties of synthesized derivatives were found in the acceptable range. In the future, these compounds can be further explored for biological activity.

Virtual screening and molecular dynamics simulations of phytochemicals targeting cofactor-independent phosphoglycerate mutase in antimicrobial-resistant Mycoplasma genitalium.

Mycoplasma genitalium (M. genitalium) poses a significant challenge in clinical treatment due to its increasing antimicrobial resistance. This study investigates alternative therapeutic approaches by targeting the cofactor-independent phosphoglycerate mutase (iPGM) enzyme with phytochemicals derived from ethnobotanical plants. In silico screening identified several promising inhibitors, with 2-carboxy-D-arabinitol demonstrating the highest binding affinity (-9.77kcal/mol), followed by gluconic acid (-9.03kcal/mol) and citric acid (-8.68kcal/mol). Further analysis through molecular dynamics (MD) simulations revealed insights into the binding mechanisms and stability of these phytochemicals within the iPGM active site. The MD simulations indicated initial fluctuations followed by stability, with intermittent spikes in RMSD values. The lowest RMSF values confirmed the stability of the ligand-protein complexes. Key residues, including Ser-61, Arg-188, Glu-62, Asp-397, and Arg-260, were found to play crucial roles in the binding and retention of inhibitors within the active pocket. These findings suggest that the identified phytochemicals could serve as novel antimicrobial agents against M. genitalium by effectively inhibiting iPGM activity.

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

Nucleoside Scaffolds and Carborane Clusters for Boron Neutron Capture Therapy: Developments and Future Perspective.

Nucleosides containing carboranes are one of the most important boron delivery agents for boron neutron capture therapy, BNCT, which are good substrates of hTK1. The development of several nucleosides containing carboranes at early stages led to the discovery of the first generation of 3CTAs by incorporating a hydrocarbon spacer between the thymidine scaffold and carborane cluster and attaching dihydroxylpropyl group on the second carbon (C2) atom of the carborane cluster (e.g., N5 and N5-2OH). Phosphorylation rate, tumor cellular uptake, and retention have been evaluated in parallel to change the length of the tether arm of spacers in these compounds. Many attempts were reported and discussed to overcome the disadvantage of the first generation of 3CTAs by a) incorporating modified spacers between thymidine and carborane clusters, such as ethyleneoxide, polyhydroxyl, triazole, and tetrazole units, b) attaching hydrophilic groups at C2 of the carborane cluster, c) transforming lipophilic closo-carboranes to hydrophilic nidocarborane. The previous modifications represented the second generation of 3CTAs to improve the hydrogen bond formation with the hTK1 active site. Moreover, amino acid prodrugs were developed to enhance biological and physicochemical properties. The structure-activity relationship (SAR) of carboranyl thymidine analogues led to the roadmap for the development of the 3rd generation of the 3CTAs for BNCT.

Tailoring the local catalytic microenvironment of metal centers NH2 groups to enhance the CO2RR performance of Ni based catalysts

Efficient catalytic reduction of the main greenhouse gas CO2 into high value-added chemicals is an important measure to alleviate the greenhouse effect and energy depletion. Metal nitrogen (M-N4) macrocyclic complexes have attracted increasing attention in the field of electrocatalytic CO2 reduction (CO2RR) due to the precise adjustment of the catalytic active site according to the requirements and the flexible modification of the external ligand structure. Nevertheless, the poor activity and low selectivity of reduction products restrict their widespread application in electrocatalytic CO2RR. Herein, a combination of nanoscale and molecular level method has been developed to construct easily obtainable 4NH2-NiPc/NH2-CNT hybrid material, in which amino groups are connected to provide electrons toward the central Ni-N4 site to promote the electrocatalytic CO2RR catalytic activity. As a result, the catalyst 4NH2-NiPc/NH2-CNT mainly produces CO in the electrocatalytic CO2RR, which exhibits a Faradaic efficiency of CO (FECO) higher than 92 % within a wide overpotential range of −0.70 to −0.95 V vs. RHE, and provides excellent stability with a current density of 12 mA cm−2 at −0.80 V vs. RHE. In addition, 4NH2-NiPc/NH2-CNT reaches its maximum FECO value of 96 % at −0.8 V vs. RHE, which is approximately 3.1 times that of the original unmodified NiPc/CNT, demonstrating excellent promotion of electrochemical performance. Similarly, compared to NiPc/CNT without amino modification, the current density of 4NH2-NiPc/NH2-CNT exceeds it by more than twice. The research results indicate that promoting role of electron substituted amino groups in catalysis dispersion and electronic environment coordination. This study proposes a promising strategy of introducing amino groups into molecular catalysts and hybridizing with carbon nanotube to enhance the electrocatalytic conversion of CO2 to deep reduction products.

Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.

Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis. Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels. Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed. In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 μM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation. Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.

Virtual Screening of Flavonoids against Plasmodium vivax Duffy Binding Protein Utilizing Molecular Docking and Molecular Dynamic Simulation.

Plasmodium vivax (P. vivax) is one of the highly prevalent human malaria parasites. Due to the presence of extravascular reservoirs, P. vivax is extremely challenging to manage and eradicate. Traditionally, flavonoids have been widely used to combat various diseases. Recently, biflavonoids were discovered to be effective against Plasmodium falciparum. In this study, in silico approaches were utilized to inhibit Duffy binding protein (DBP), responsible for Plasmodium invasion into red blood cells (RBC). The interaction of flavonoid molecules with the Duffy antigen receptor for chemokines (DARC) binding site of DBP was investigated using a molecular docking approach. Furthermore, molecular dynamic simulation studies were carried out to study the stability of top-docked complexes. The results showed the effectiveness of flavonoids, such as daidzein, genistein, kaempferol, and quercetin, in the DBP binding site. These flavonoids were found to bind in the active region of DBP. Furthermore, the stability of these four ligands was maintained throughout the 50 ns simulation, maintaining stable hydrogen bond formation with the active site residues of DBP. The present study suggests that flavonoids might be good candidates and novel agents against DBP-mediated RBC invasion of P. vivax and can be further analyzed in in vitro studies.

A Rationalized Approach to Design and Discover Novel Non-steroidal Derivatives through Computational Aid for the Treatment of Prostate Cancer.

Prostate cancer is one of the most prevalent cancers in men, leading to the second most common cause of death in men. Despite the availability of multiple treatments, the prevalence of prostate cancer remains high. Steroidal antagonists are associated with poor bioavailability and side effects, while non-steroidal antagonists show serious side effects, such as gynecomastia. Therefore, there is a need for a potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effects, and minimal side effects. This current research work focused on identifying a novel non-steroidal androgen receptor antagonist through computational tools, such as docking and in silico ADMET analysis. Molecules were designed based on a literature survey, followed by molecular docking of all designed compounds and ADMET analysis of the hit compounds. A library of 600 non-steroidal derivatives (cis and trans) was designed, and molecular docking was performed in the active site of the androgen receptor (PDBID: 1Z95) using Auto- Dock Vina 1.5.6. Docking studies resulted in 15 potent hits, which were then subjected to ADME analysis using SwissADME. ADME analysis predicted three compounds (SK-79, SK-109, and SK-169) with the best ADME profile and better bioavailability. Toxicity studies using Protox-II were performed on the three best compounds (SK-79, SK-109, and SK-169), which predicted ideal toxicity for these lead compounds. This research work will provide ample opportunities to explore medicinal and computational research areas. It will facilitate the development of novel androgen receptor antagonists in future experimental studies.

Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi-enzyme colocalization and environment.

Millions of years of evolution have optimized many biosynthetic pathways by use of multi-step catalysis. In addition, multi-step metabolic pathways are commonly found in and on membrane-bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast-ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl-CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol-O-acetyltransferase. Arranging two enzymes with the smallest inter-enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter-enzyme distances. When the off-target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi-enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems.

Design, Synthesis, and in vitro Evaluation of Derivatives of Quinoxaline-2- One as a Myeloperoxidase Modulator Using in silico Methods

Background: In some pathological situations, the overproduction of oxidising agents also results in oxidative damage to host cell proteins and DNA, which induces abnormal expression of inflammatory cytokines and chemokines. A recently discovered biomarker of inflammation is myeloperoxidase. Various inflammatory conditions cause the release of this enzyme into the extracellular environment. Objective: Our study aimed to design, synthesize, and in vitro evaluate derivatives of quinoxaline- 2-one as a myeloperoxidase modulator using in silico methods. Methods: A series of quinoxaline-2-one derivatives was synthesized and characterized by various analytical techniques. Further, to confirm and explore the molecular mechanism, an in silico docking study against the myeloperoxidase enzyme was performed (PDB ID: 1DNU). Results: The compounds Q1, Q2, and Q5 showed better antioxidant activity in the DPPH assay, whereas the nitric oxide scavenging assay showed the compounds Q2, Q4, and Q5 had significant activity when compared to the standard IC50 value (28.8 μg/ml). Besides, the anti-inflammatory studies showed the compounds Q1, Q3, and Q5 had better inhibition (89.79%) when compared to the standard drug aceclofenac (85.37%) at 1000 μg/ml concentration. The top three ligands for myeloperoxidase (PDB ID: 1DNU) with the highest scores in activity were found as Q2, Q1, and Q5, with scores of -13.2838, -12.5841, and -11.6906 Kcal/mol, respectively. The compounds were efficiently bound to the myeloperoxidase active site with arene-arene, arene-cation, and hydrogen bonding interactions. Conclusion: By introducing the various heterocyclic rings and deactivating and activating groups, we may produce a newer class of candidates for many infectious diseases. Thus, from the computational studies carried out, we may obtain hints for optimising the molecular selectivity of the quinoxaline-2-one derivatives to provide help in the design of new compounds for effective myeloperoxidase enzyme modulators. However, further pharmacokinetics, pharmacodynamics, preclinical, and clinical studies permit the design of the new agents without undesirable interactions.

Tandem Oxidation Activation of Carbon for Enhanced Electrochemical Synthesis of H2O2: Unveiling the Role of Quinone Groups and Their Operando Derivatives

AbstractOxygen‐doped carbon materials show great promise to catalyze two‐electron oxygen reduction reaction (2e‐ORR) for electrochemical synthesis of hydrogen peroxide (H2O2), but the identification of the active sites is the subject of ongoing debate. In this study, a tandem oxidation strategy is developed to activate carbon black for achieving highly efficient electrochemical synthesis of H2O2. Acetylene black (AB) is processed with O2 plasma and subsequent electrochemical oxidation, resulting in a remarkable selectivity of >96% over a wide potential range, and a record‐setting high yield of >10 mol gcat−1 h−1 with good durability in gas diffusion electrode. Comprehensive characterizations and calculations revealed that the presence of abundant C═O groups at the edge sites positively correlated to and accounted for the excellent 2e‐ORR performance. Notably, the edge hydroquinone group formed from quinone under operando conditions, which is overlooked in previous research, is identified as the most active catalytic site.

Biological characterisation and computational conformation dynamics of putative L-glutaminase YLaM identified from Bacillus licheniformis

ABSTRACT Glutaminases are a unique group of hydrolytic enzymes with potential applications in cancer therapy and the food industry. This study focused on the biological characterisation and computational conformation dynamics of YLaM, a potential L-glutaminase from a halothermotolerant Bacillus licheniformis. The research integrated experimental and computational methods to identify the YLaM sequence and predict its structural and functional properties. YLaM was amplified using a polymerase chain reaction, cloned into a pET-22b(+) vector, sequenced, and submitted to BankIt/NCBI. This experimental work was complemented by in silico analysis, including structural modelling via the I-TASSER web server, molecular docking using AutoDockTools 1.5.6, and molecular dynamic (MD) simulations using GROMACS v5.1.4. The study resulted in the development of a high-quality 3D model of YLaM through homology modelling and structural refinement, enabling a detailed exploration of its binding affinity with L-glutamine (L-Gln). By identifying active site residues using the homotetramer structure of human glutaminase, crucial interactions with L-Gln were validated, confirming its catalytic function. Finally, MD simulations confirmed the stability of the complex under physiological conditions. This combined molecular identification and functional simulations provide comprehensive insights into the physicochemical properties of the enzyme, offering valuable information for subsequent assessments, including recombinant production and biological impact evaluations.

In Situ Surfaced Mn-Mn Dimeric Sites Dictate CO Hydrogenation Activity and C2 Selectivity over MnRh Binary Catalysts.

Massive ethanol production has long been a dream of human society. Despite extensive research in past decades, only a few systems have the potential of industrialization: specifically, Mn-promoted Rh (MnRh) binary heterogeneous catalysts were shown to achieve up to 60% C2 oxygenates selectivity in converting syngas (CO/H2) to ethanol. However, the active site of the binary system has remained poorly characterized. Here, large-scale machine-learning global optimization is utilized to identify the most stable Mn phases on Rh metal surfaces under reaction conditions by exploring millions of likely structures. We demonstrate that Mn prefers the subsurface sites of Rh metal surfaces and is able to emerge onto the surface forming MnRh surface alloy once the oxidative O/OH adsorbates are present. Our machine-learning-based transition state exploration further helps to resolve automatedly the whole reaction network, including 74 elementary reactions on various MnRh surface sites, and reveals that the Mn-Mn dimeric site at the monatomic step edge is the true active site for C2 oxygenate formation. The turnover frequency of the C2 product on the Mn-Mn dimeric site at MnRh steps is at least 107 higher than that on pure Rh steps from our microkinetic simulations, with the selectivity to the C2 product being 52% at 523 K. Our results demonstrate the key catalytic role of Mn-Mn dimeric sites in allowing C-O bond cleavage and facilitating the hydrogenation of O-terminating C2 intermediates, and rule out Rh metal by itself as the active site for CO hydrogenation to C2 oxygenates.

Reactivity Inside Molecular Flasks: Acceleration Modes and Types of Selectivity Obtainable

There is increasing interest in the discovery and application of molecular flasks ‐ supramolecular host structures capable of catalyzing organic reactions. Reminiscent of enzymes due to possessing a host cavity akin to an active site, molecular flasks can exhibit complex catalytic mechanisms and in many cases provide selectivity not achievable in bulk solvent. In this Review, we aim to organize the increasingly diverse examples through a two‐part structure. In part one, we provide an overview of the different acceleration modes that operate within molecular flasks, while in part two we showcase, through selected examples, the different types of selectivity that are obtainable through the use of molecular flasks. Particular attention is given to examples that are relevant to current challenges in synthetic organic chemistry. We believe that this structure makes the field more approachable and thus will stimulate the development of novel applications of molecular flasks.

Polyoxometalate‐Based Single‐Atom Catalyst with Precise Structure and Extremely Exposed Active Site for Efficient H2 Evolution

Single‐atom catalysts with precise structure and extremely high catalytic efficiency remain a fervent focus in the fields of materials chemistry and catalytic science. Herein, a nickel‐substituted polyoxometalate (POM) {NiSb6O4(H2O)3[β‐Ni(hmta)SbW8O31]3}15‐ (NiPOM) with one extremely exposed nickel site [NiO3(H2O)3] was synthesized using the conventional aqueous method. The uniform dispersion of single nickel center with well‐defined structure was facilely achieved by anchoring nanosized NiPOM on graphene oxide (GO). The resulting NiPOM/GO can couple with CdS photoabsorber for the construction of low‐cost and ultra‐efficient hydrogen evolution system. The H2 yield can reach to 2753.27 mmol gPOM‐1 h‐1, which represents a record value among all the POM‐based photocatalytic systems. Remarkablely, an extremely high hydrogen yield of 3647.28 mmol gPOM‐1 h‐1 was achieved with simultaneous photooxidation of commercial waste plastic, representing the first POM‐based photocatalytic system for H2 evolution and waste plastic conversion. This work highlights a straightforward strategy for constructing extremely exposed single‐metal site with precise microenvironment by facilely manipulating nanosized molecular cluster to control individual atom.

Determinants of maturation of the Staphylococcus aureus autoinducing peptide.

The accessory gene regulatory (Agr) system is required for virulence factor gene expression and pathogenesis of Staphylococcus aureus. The Agr system is activated in response to the accumulation of a cyclic autoinducing peptide (AIP), which is matured and secreted by the bacterium. The precursor of AIP, AgrD, consists of the AIP flanked by an N-terminal [Formula: see text]-helical Leader and a charged C-terminal tail. AgrD is matured to AIP by the action of two proteases, AgrB and MroQ. AgrB cleaves the C-terminal tail and promotes the formation of a thiolactone ring, whereas MroQ cleaves the N-terminal Leader in a manner that depends on the four-amino acid linker immediately following a conserved IG helix breaker motif. However, the attributes of AgrD that dictate the sequence of events in peptide maturation are not fully defined. Here, we used engineered AgrD peptide intermediates to ascertain the sufficiency of MroQ for N-terminal peptide cleavage, peptide export, and generation of mature AIP. We found that MroQ promotes the removal of the N-terminal Leader peptide from both linear and cyclic peptide intermediates, while peptide cyclization remained essential for signaling. The expression of the Leader peptide in isolation was sufficient for MroQ-dependent cleavage proximal to the four-amino-acid linker. In addition, active site mutations within AgrB destabilized full-length AgrD and thiolactone-containing intermediates and prevented the release of the Leader peptide. Altogether, our data support a tandem peptide maturation event involving both MroQ and AgrB that appears to couple protease activity and export of bioactive AIP.IMPORTANCEThe accessory gene regulatory (Agr) system is important for S. aureus pathogenesis. Activation of the Agr system requires recognition of a cyclic peptide pheromone, which must be fully matured to exert its biological activity. The complete events in cyclic peptide maturation and export from the bacterial cell remain to be fully defined. We and others recently discovered that the membrane peptidase MroQ is required for pheromone maturation. This study builds off the identification of MroQ and considers the attributes of the pheromone pro-peptide that are required for MroQ-mediated processing as well as uncovers features important for peptide stability and export. Overall, the findings in this study have implications for understanding bacterial pheromone maturation and virulence.

Hydrogenation‐Rearrangement of Furfural over Cu‐based Catalysts with Abundant Lewis Acid Sites

AbstractCyclopentanone (CPO) and cyclopentanol (CPL), derived from renewable biomass resource hemicellulose, are considered sustainable chemicals that can substitute fossil‐based products, which could be obtained through the hydrogenation‐rearrangement reaction of furfural (FFA). However, the inevitable condensation reactions of FFA and furfuryl alcohol (FA) in aqueous solutions generate humins and result in carbon loss, limiting the industrial application of this process. Herein, a series of Cu‐based catalysts were synthesized using the reverse co‐precipitation method with various metal promoters and applied in the FFA hydrogenation‐rearrangement reaction. The highest yield of 97.1 % CPO/CPL achieved in a typical reaction condition at 200 °C, 4 MPa, in 20 wt % isopropanol‐water mixed solvent over CuZnZr catalyst and the recyclability test confirmed that the catalyst had excellent stability. Experimental studies and characterizations showed that the enhanced performance could be attributed to the adequate Lewis acid sites, regulated through the synergistic interaction between Cu, Zn, and Zr compounds. The simultaneous introduction of Zn and Zr promotes the Cu reduction, and results in more dispersed Cu0 and Cu+, providing an ample and reliable active site. This study outlines a viable method for the catalyst designing and valorizing biomass into high‐value‐added products.

Computational Simulation Studies, Synthesis, In Vitro, and In Vivo Evaluation of Heterocyclically Substituted Glycinamide Derivatives as DPP 4 Inhibitors

AbstractAccording to the International Diabetes Federation, the global prevalence of diabetes is projected to increase to 643 million individuals by 2030 and 783 million by 2045. DPP 4 inhibitors approved by regulatory authorities worldwide, efficiently to regulate high blood sugar levels by impeding the degradation of glucagon like peptide‐1 (GLP‐1), an incretin hormone, prolonging the physiological effects of GLP‐1. In the present research work, a total of 12 glycinamide‐based compounds with aromatic substituents on the N‐terminus and heterocycles like piperidine, 4‐phenylpiperazine, and 6‐fluorobenzo[d]isoxazol‐3‐piperidine on the C‐terminus were synthesized and characterized. The synthesized compounds were subjected to in vitro DPP 4 inhibition assay. The promising compound JAG‐D2 was evaluated in vivo using OGTT assay in streptozotocin‐induced diabetic rats. JAG‐D2 produced a significant reduction in blood glucose levels at 20 mg/kg and 40 mg/kg doses when compared with a 1 mg/kg dose of the reference standard sitagliptin. The synthesized compounds occupied the active site of DPP 4 as demonstrated in molecular docking and MM‐GBSA analysis for rescoring on the basis of binding free energy. Molecular dynamics studies displayed the stability of the docked pose of JAG‐D2 in the catalytic site of DPP 4. All compounds exhibited compliance with Lipinski's rule of five, suggesting drug‐like properties.

Polyoxometalate‐Based Single‐Atom Catalyst with Precise Structure and Extremely Exposed Active Site for Efficient H2 Evolution

Single‐atom catalysts with precise structure and extremely high catalytic efficiency remain a fervent focus in the fields of materials chemistry and catalytic science. Herein, a nickel‐substituted polyoxometalate (POM) {NiSb6O4(H2O)3[β‐Ni(hmta)SbW8O31]3}15‐ (NiPOM) with one extremely exposed nickel site [NiO3(H2O)3] was synthesized using the conventional aqueous method. The uniform dispersion of single nickel center with well‐defined structure was facilely achieved by anchoring nanosized NiPOM on graphene oxide (GO). The resulting NiPOM/GO can couple with CdS photoabsorber for the construction of low‐cost and ultra‐efficient hydrogen evolution system. The H2 yield can reach to 2753.27 mmol gPOM‐1 h‐1, which represents a record value among all the POM‐based photocatalytic systems. Remarkablely, an extremely high hydrogen yield of 3647.28 mmol gPOM‐1 h‐1 was achieved with simultaneous photooxidation of commercial waste plastic, representing the first POM‐based photocatalytic system for H2 evolution and waste plastic conversion. This work highlights a straightforward strategy for constructing extremely exposed single‐metal site with precise microenvironment by facilely manipulating nanosized molecular cluster to control individual atom.