Active Site Research Articles

Cooperative Photometallobiocatalysis: Nonheme Fe-Enzyme-Catalyzed Enantioconvergent RadicalDecarboxylative Azidation, Thiocyanation and Isocyanation of Redox-Active Esters.

Cooperative catalysis with an enzyme and a smallmolecule photocatalyst has very recently emerged as a potentially general activation mode to advance novel biocatalytic reactions with synthetic utility. Herein, we report cooperative photobiocatalysis involving an engineered nonheme Fe enzyme and a tailored photoredox catalyst as a unifying strategy for the catalytic enantioconvergent decarboxylative azidation, thiocyanation and isocyanation of redox-active esters via a radical mechanism. Through the survey and directed evolution of nonheme Fe enzymes, we repurposed and further evolved metapyrocatechase (MPC), a nonheme Fe extradiol dioxygenase not previously studied in new-tonature biocatalysis, for the enantioselective C-N3, C-SCN and C- NCO bond formation through a radical rebound mechanism with an enzymatic Fe-X intermediate (X = N3, NCS, and NCO). A range of primary, secondary and tertiary alkyl radical precursors were effectively converted by our engineered MPC, allowing the syntheses of organic azides, thiocyanates and isocyanates with good to excellent enantiocontrol. Further chemical derivatization of these products furnished valuable compounds. Computational studies via DFT and MD simulations shed light on the mechanism as well as the binding poses of the alkyl radical intermediate in the enzyme active site and the π-facial selectivity in the enantiodetermining radical rebound.

Precise Control of Active Site Configurations in High-entropy Intermetallic Compounds for Electrocatalytic Nitrate Reduction to Ammonia.

High-entropy alloys (HEAs), composed of five or more elements in similar proportions, exhibit unique physicochemical properties, but their disordered atomic structures pose challenges in the precise control of active sites. In contrast, high-entropy intermetallic compounds (HEIs), with an ordered atomic arrangement and well-defined atomic positions, provide clear active site configurations, making them particularly advantageous for complex electrocatalytic reactions like the nitrate reduction reaction (NITRR). Herein, we present the FeCoNiGeSb-HEI with precisely controlled elemental distributions, leading to the formation of distinct active sites. The FeCoNiGeSb-HEI catalyst exhibits high activity for NITRR, achieving a high NH3 yield rate of 7.5 mg h-1 cm-2 at -0.4 V and a Faradaic efficiency (FE) of 97.6% at -0.30 V, along with excellent stability. Density functional theory (DFT) calculations and experimental results reveal that Co sites act as key active sites, while Fe and Ni atoms contribute a synergistic effect. Additionally, the FeCoNiGeSb-HEI catalyst functions in a bifunctional system coupling NH3 production with the glycerol oxidation reaction (GOR), achieving an NH3 yield of 9.8 mg h-1 cm-2 at 1.8 V, maintaining stable performance for 100 hours.

A thermostable bacterial metallohydrolase that degrades organophosphate plasticizers.

A cyclase-phosphotriesterase (C-PTE) from Ruegeria pomeroyi DSS-3 has recently been identified for its capacity to detoxify several organophosphate compounds. However, several aspects of this enzyme remain unexplored, such as its activity with industrial organophosphates, its molecular structure and its thermostability. In this work, we report the crystal structure of C-PTE, which was solved to 2.3 Å resolution, providing insight into the enzyme's mechanism of action, revealing a binuclear Zn2+ active site and distant similarity to other phosphotriesterases from the amidohydrolase superfamily. We show that C-PTE catalyzes the hydrolysis of the OP plasticizers triphenyl phosphate (TPhP) and tris(2- chloropropyl) phosphate (TCPP), albeit with low efficiency, but not the sterically bulkier tri-otolyl phosphate (ToTP). Finally, we show that, even though Ruegeria pomeroyi DSS-3 is not a thermophile, C-PTE exhibits remarkable thermostability and retains structure up to 90 °C. Overall, our findings advance our understanding of C-PTE, suggest that it is a good candidate for engineering owing to its thermostability and that it could contribute to bioremediation strategies to reduce the impact of pollution by industrial organophosphates.

An epimer of threose nucleic acid enhances oligonucleotide exonuclease resistance through end capping

End capping of oligonucleotides by modified nucleotides is essential for boosting resistance to 3’ exonuclease degradation, thereby enhancing their stability and therapeutic efficacy in vivo. However, the rationale behind these modifications remains unclear. In this study, we designed a novel nucleic acid analog, eTNA, by replacing deoxyribose with the α-D-erythrofuranosyl moiety. As an epimer of TNA (threose nucleic acid), it combines structural features from inverted-dT and TNA, both known for enhancing resistance against 3’-exonucleases. On top of this, we systematically investigated the stability of a series of oligonucleotides capped with inverted-dT, TNA and eTNA at the 5’-, 3’-, or both ends. The structural differences between eTNA and natural dT help to understand how the sugar ring’s conformation and rigidity affect duplex stability and exonuclease resistance. Our experimental and theoretical results show that the modified furanose affects the binding positions of terminal nucleotides in the phosphodiesterase active site, preventing phosphodiester hydrolysis. Our mechanistic study should benefit future therapeutic oligonucleotide design with end capping.

Molecular identification and functional characterization of a chitinase gene in Picea asperata

Plant chitinase, a member of the pathogenesis-related proteins and glycoside hydrolase family 19, plays a crucial role in plant resistance to pathogenic fungi. In this study, we isolated a chitinase gene encoding PaChi from Picea asperata, containing an open reading frame of 768 bp that encodes 255 amino acid residues. PaChi includes the chitin-binding domain, catalytic domain, and active site characteristic of class IV chitinases. Homologous modeling and phylogenetic analysis indicated that PaChi exhibits the highest structural similarity and closest genetic relationship with the chitinase of Norway spruce, suggesting potential functional similarities. RT-qPCR analysis demonstrated that PaChi expression is relatively high in the roots of P. asperata. Additionally, PaChi transcription levels were significantly upregulated during the early stages of Lophodermium piceae infection, indicating active involvement in the defense response of P. asperata against L. piceae infection. SDS-PAGE analysis revealed that the recombinant PaChi has a molecular weight of approximately 27 kDa. The purified recombinant PaChi exhibited a chitinase activity of 4.61 U/mg, with optimal pH and temperature at 7.0 and 40 °C, respectively. Notably, purified recombinant PaChi significantly affected the mycelial morphology of L. piceae, inclusion body concentration and cell swelling. These findings lay the groundwork for further understanding the molecular mechanisms by which PaChi is involved in biological stress.

Design, synthesis, biological assessments and computational studies of 3-substituted phenyl quinazolinone derivatives as promising anti-cancer agents

A new series of 3-substituted phenyl quinazolinone derivatives were designed and synthesized as anti-cancer agents. The most potent derivative with IC50 values of 12.84 ± 0.84 and 10.90 ± 0.84 µM against MCF-7 and SW480 cell lines was comparable to Cisplatin and Erlotinib as positive controls. Cell cycle analysis showed that the most active compound could arrest at S phase in MCF-7 breast cancer cells. The apoptosis assay demonstrated the induction of apoptosis in the MCF-7 cell line, too. Molecular docking results showed better accommodation of the most active compound through hydrogen bonding interaction in the binding site of EGFR enzyme. Molecular dynamics simulations for the potent analogue demonstrated well binding stability compared to the less active analogue, with a lower RMSD, Rg and more interactions with the original active site residues. DFT calculations were performed on the active and inactive compounds, using Gaussian 09 at the M06-2X/6–31 + G(d) theoretical level. ADME (Absorption, Distribution, Metabolism, and Excretion) properties showed that most of the compounds are in acceptable range of Lipiniski rule. These findings underscore the potential of the synthesized compounds as potent cytotoxic inhibitors and provide insights for developing effective treatments for cancer therapy.

Challenge and Chance of Single Atom Catalysis: The Development and Application of the Single Atom Site Catalysts Toolbox.

ConspectusSingle atom catalysis has garnered widespread attention in the past decade. In general, single atom catalysis refers to a catalytic process involving the participation of single atom sites. A single atom site refers to an active site with only one metal atom playing the main role in the catalysis process. This metal atom is usually coordinated by other atoms in the active site and anchored on the support. Heterogeneous catalysts in which all active sites are single atom sites are referred to as single atom site catalysts (SASCs). Owing to their distinctive active site architecture, single atom catalysis has shown ultrahigh atomic utilization efficiency and unique catalytic activity and selectivity in many systems such as thermal catalysis, electrocatalysis, and environmental catalysis.However, the preparation of SASCs poses significant challenges as metal species tend to sinter and agglomerate during high-temperature treatment. In the past decade, we have challenged the controllable preparation of SASCs based on more than ten years of experience in nanomaterial synthesis. Several representative SASC preparation strategies have been proposed by our group, such as pyrolysis of MOFs with metal ions doped in the skeleton, M@ZIF-8 with a metal precursor fixed by the host-guest interaction, and M/N-rich support precursors. Additionally, "top-down" strategies starting from metal nanoparticles have been established. Based on these synthetic strategies, a systematic SASCs toolbox has been successfully built.In addition to the SASCs, we have expanded the toolbox to include the dual-atom-site catalysts (DASCs) (including active sites with dual active metal atoms or including dual kinds of single atom sites) and nanosingle-atom-site catalysts (NSASCs) (catalysts with both single atom sites and nanoparticle/cluster sites). With the help of a variety of "tools" in the toolbox, single atom catalysis has shown its application value in many important processes such as bulk chemical catalysis, fine chemical catalysis, energy catalysis, and environmental catalysis. Based on laboratory-scale research, we further explored the feasibility of single atom catalysis in industrial catalysis and successfully applied single atom catalysis to industrial-level automobile exhaust purification, which will soon achieve commercialization.This Account provides a concise overview of the evolution of single atom catalysis, summarizes the preparation strategies for SASCs pioneered by our group over the past decade, and highlights the SASCs toolbox developed through these strategies. We also showcase the practical applications of the SASCs toolbox in key catalytic fields, highlight our progress in advancing the industrialization of single atom catalysis (particularly for automobile exhaust purification), and discuss the future prospects of single atom catalysis in industrial applications.

The Lysine Deprotonation Mechanism in a Ubiquitin Conjugating Enzyme.

Ubiquitination is a biochemical reaction in which a small protein, ubiquitin (Ub), is covalently linked to a lysine on a target protein. This type of post-translational modification can signal for protein degradation, DNA repair, or inflammation response. Ubiquitination is catalyzed by three families of enzymes: ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2), and ubiquitin ligases (E3). In this study, we focus on the chemical mechanism used by the E2 enzyme, Ubc13, which forms polyubiquitin chains by linking a substrate Ub to Lys63 on a target ubiquitin (Ub*). Initially, Ubc13 is covalently linked to the substrate Ub. Next, Lys63 in the Ub* is deprotonated, becomes an active nucleophile, and attacks the thioester bond in the Ubc13∼Ub conjugate. The deprotonation mechanism is not well understood. There are two, conserved nearby residues that may act as conjugate bases (Asp119 on Ubc13 and Glu64 on Ub*.) It is also hypothesized that the active site environment suppresses the lysine's pKa, favoring deprotonated lysine. We test these hypotheses by simulating both WT and mutant Ubc13 with constant pH molecular dynamics (CpHMD), which allows titratable residues to change their protonation states. In our simulations, we have five titratable residues, including Lys63, and we use these simulations to monitor the protonation states and to generate titration curves of lysine 63. We found that the pKa of Lys63 is highly dependent on its distance from the active site. Also, mutating Asp119 or Glu64 to Ala has little effect on the lysine pKa, indicating that neither residue acts as a generalized base. Finally, we note that mutating a structural residue (Asn79 to Ala) increases the lysine pKa, suggesting that alterations to the active site hydrogen bonding network can affect nucleophile activation.

Engineered Spatial Confinement of Cu Single‐atoms with Diagonal N–Cu–N Motifs for High‐rate CO2 Methanation

The renewable‐electricity‐powered carbon dioxide reduction (eCO2R) to value‐added fuels and feedstocks like methane (CH4) holds the sustainable and economically viable carbon cycle at meaningful scales. However, this kinetically challenging eight‐electron multistep deep‐reduction encounters insufficient catalyst design principles to steer complex CO2 reduction pathways. Utilizing atomic copper (Cu) structures with unitary active site can boost eCO2R‐to‐CH4 selectivity due to the efficient suppression of unwanted C−C coupling. Herein, we report a sequential ion exchange strategy to fabricate periodic Cu single‐atom catalysts within a polymeric carbon nitride (PCN) matrix, where the uniformly dispersed, diagonally coordinated N–Cu–N configuration hosts low‐valent Cuδ+ centers. Leveraging the periodic N‐anchoring sites with delocalized π‐electron conjugation in PCN matrix, the isolated Cu sites are obtained with an interatomic distance of ~4.2 Å under high metal‐loading conditions. This engineered spatial configuration effectively inhibits C−C coupling to avoid subsequent multicarbon products formation. The optimized Cu1/PCN demonstrates exceptional eCO2R‐to‐CH4 performance, achieving 71.1% CH4 Faradaic efficiency with a high partial current density of 426.6 mA cm−2 at −1.50 V vs. reversible hydrogen electrode, outpacing the state‐of‐the‐art catalysts. This work delves into effective concepts for steering desirable reaction pathways via precisely modulating active site structures at the atomic level to create favorable microenvironments.

Engineered Spatial Confinement of Cu Single-atoms with Diagonal N-Cu-N Motifs for High-rate CO2 Methanation.

The renewable-electricity-powered carbon dioxide reduction (eCO2R) to value-added fuels and feedstocks like methane (CH4) holds the sustainable and economically viable carbon cycle at meaningful scales. However, this kinetically challenging eight-electron multistep deep-reduction encounters insufficient catalyst design principles to steer complex CO2 reduction pathways. Utilizing atomic copper (Cu) structures with unitary active site can boost eCO2R-to-CH4 selectivity due to the efficient suppression of unwanted C-C coupling. Herein, we report a sequential ion exchange strategy to fabricate periodic Cu single-atom catalysts within a polymeric carbon nitride (PCN) matrix, where the uniformly dispersed, diagonally coordinated N-Cu-N configuration hosts low-valent Cuδ+ centers. Leveraging the periodic N-anchoring sites with delocalized π-electron conjugation in PCN matrix, the isolated Cu sites are obtained with an interatomic distance of ~4.2 Å under high metal-loading conditions. This engineered spatial configuration effectively inhibits C-C coupling to avoid subsequent multicarbon products formation. The optimized Cu1/PCN demonstrates exceptional eCO2R-to-CH4 performance, achieving 71.1% CH4 Faradaic efficiency with a high partial current density of 426.6 mA cm-2 at -1.50 V vs. reversible hydrogen electrode, outpacing the state-of-the-art catalysts. This work delves into effective concepts for steering desirable reaction pathways via precisely modulating active site structures at the atomic level to create favorable microenvironments.

Development of hazelnut shell-derived biochar to support a bifunctional MoCo electrocatalyst for HER/OER in alkaline medium

Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), the two concurrent reactions for the electrolytic production of green H2, require low-cost and sustainable electrocatalysts for their scale-up, as for example non-noble metals and carbonaceous structures with high surface area. Our hypothesis is that the activated-doped biochar decorated with Mo and Co provides high porosity and active site dispersion, enhancing HER and OER kinetics with low overpotentials and high stability in an alkaline medium. Here, a bifunctional Mo/Co electrocatalyst supported on N-doped biochar obtained from hazelnut shells has been developed, thus valorizing an agro-industrial residue of major importance in Chile. The activated biochar matrix, with interconnected hierarchical pores, offered a high surface area of 1102 m2 g−1 and ID/IG = 1.08 graphitization, while N-doping was observed by XPS, with the formation of N-pyridinic and N-graphitic functionalities that improved the catalytic performance. The addition of metals to the substrate allowed the formation of bimetallic Mo/Co active sites (Co6Mo6C), increasing the graphitization degree and improved the growth of these bimetallic sites. The electrocatalytic performance in the presence of the metals was good, revealing low overpotentials for HER (0.257 V) and OER (0.370 V) with low Tafel slopes (51 and 59 mV dec−1, respectively) under alkaline conditions, also improving the electron transfer and stability.Graphical

A deep learning and molecular modeling approach to repurposing Cangrelor as a potential inhibitor of Nipah virus

Deforestation, urbanization, and climate change have significantly increased the risk of zoonotic diseases. Nipah virus (NiV) of Paramyxoviridae family and Henipavirus genus is transmitted by Pteropus bats. Climate-induced changes in bat migration patterns and food availability enhances the virus’s adaptability, in turn increasing the potential for transmission and outbreak risk. NiV infection has high human fatality rate. With no antiviral drugs or vaccines available, exploring the complex machinery involved in viral RNA synthesis presents a promising target for therapy. Drug repurposing provides a fast-track approach by identifying existing drugs with potential to target NiV RNA-dependent RNA polymerase (L), bypassing the time-consuming process of developing novel compounds. To facilitate this, we developed an attention-based deep learning model that utilizes pharmacophore properties of the active sites and their binding efficacy with NiV L protein. Around 500 FDA-approved drugs were filtered and assessed for their ability to bind NiV L protein. Compared to the control Remdesivir, we identified Cangrelor, an antiplatelet drug for cardiovascular diseases, with stronger binding affinity to NiV L (glide score of -12.30 kcal/mol). Molecular dynamics simulations further revealed stable binding (RMSD of 3.54 Å) and a post-MD binding energy of -181.84 kcal/mol. The strong binding of Cangrelor is illustrated through trajectory analysis, principal component analysis, and solvent accessible surface area, further confirming the stable interaction with the active site of NiV RdRp. Cangrelor can interact with NiV L protein and may potentially interfere with its replication. These findings suggest that Cangrelor will be a potential drug candidate that can effectively interact with the NiV L protein and potentially disrupt the viral replication. Further in vivo studies are warranted to explore its potential as a repurposable antiviral drug.

Steric and energetic studies on adsorption of toxic arsenic ions by hematite nano-rods from laterite highlighting the impact of modification periods

This study presents a facile, cost-effective hydrothermal transformation of natural lateritic iron ore into hematite nanorods, offering significant economic and technical benefits for the remediation of toxic arsenic ions. Lateritic iron ore was subjected to alkaline modification for different durations (12 h (HM12), 24 h (HM24), 36 h (HM36), and 48 h (HM48)), leading to morphological evolution into nanorod structures (2D) with variations in surface area, crystallinity, and adsorption efficacy for arsenate (As(V)) ions. Comprehensive characterization confirmed significant structural and physicochemical modifications. X-ray diffraction (XRD) analysis revealed a shift in peak positions and intensity reduction, indicative of lattice strain and increased surface defects. Fourier-transform infrared spectroscopy (FT-IR) confirmed modifications in the Fe–O coordination, and Brunauer–Emmett–Teller (BET) surface area analysis demonstrated a notable increase in surface area, with HM36 exhibiting the highest value (154.7 m2/g). Adsorption experiments indicated that HM36 achieved the highest As(V) removal capacity (151.4 mg/g), followed by HM48 (138.2 mg/g), HM24 (125.4 mg/g), and HM12 (113.8 mg/g). Advanced equilibrium modeling revealed steric and energetic parameters governing the adsorption mechanism, with HM36 exhibiting the highest density of active sites (Nm = 67.9 mg/g). Each active site accommodated up to three As(V) ions, emphasizing the significance of multi-ionic interactions and vertical stacking at the adsorption interface. The adsorption energy, evaluated using both classic models (< 4 kJ/mol) and advanced statistical physics models (< 9 kJ/mol), confirmed a predominantly physical and exothermic adsorption mechanism. Thermodynamic evaluations further supported the spontaneous and favorable nature of As(V) adsorption across all modified hematite derivatives. The ease of synthesis, low-cost natural precursor, improved adsorption efficiency, and recyclability highlight the potential application of these hematite nanorods in real-world wastewater remediation. The findings suggest that HM36 is a highly efficient and scalable adsorbent for arsenic removal, offering sustainable solutions for industrial and agricultural wastewater treatment.

Novel indazole Schiff base metal chelates as potential antifungal agents: synthesis, characterization, and computational analysis

Soil-borne phytopathogenic fungi pose a significant risk to many economically important crops due to their ability to survive in the soil for extended periods without a host. Thus, a novel Schiff base (HL), 3-(1H-indazol-5-ylimino)-1-phenylbut-1-en-1-ol, was synthesized by the condensation of 5-aminoindazole with benzoyl acetone. Its Co2+, Ni2+, and Cu2+ chelates were also synthesized. These compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, UV–Vis, EI–mass spectroscopy, XRD, TGA, magnetic susceptibility, elemental analysis, and molar conductance. The ligand possesses an enol form and functions as a monobasic bidentate through the deprotonated OH and C=N groups. The Co2+ and Ni2+ ions produced 1:1 (M:L) chelates, whereas Cu2+ ion produced a 1:2 (M:L) chelate. From the characterization results and the DFT method, it was revealed that the Co2+ chelate has tetrahedral geometry, while Ni2+ and Cu2+ chelates are octahedral. The antifungal activities of the ligand and the metal chelates were evaluated against some plant pathogenic fungi, namely, Stromatinia cepivora, Botrytis allii, Rhizoctonia solani, and Sclerotinia sclerotiorum in comparison with the commercial fungicide Tebuconazole. The Ni+2 chelate emerged as the most potent agent that achieved 100% inhibition for the S. cepivora and S. sclerotiorum. It also caused significant morphological alterations in S. sclerotiorum as revealed by the SEM micrograph. The treated S. sclerotiorum hyphae displayed irregular, shriveled, and collapsed structures in contrast to the smooth and robust appearance of the control. The molecular docking study further confirmed that Ni2+ chelate strongly interacted with the active site of CYP51 protein compared with Co2+ and Cu2+ chelates and the fungicide Tebuconazole. The superior efficacy of Ni2+ chelate offers a promising alternative to traditional fungicides.Graphical

The Role of a Glucal-Based Molecule in the Reduction of Pancreatic Adenocarcinoma—An In Vitro and In Silico Approach

Background/Objectives: Pancreatic cancer is the seventh most lethal type of cancer in the world, and its treatment, which is largely inefficient, is based on surgery and/or non-specific chemotherapy. Its malignant features are characterized by complex cell signaling pathways, which can be used as targets for new drugs. Methods: In this study, glucal-based compounds were synthetized, with substitution based on fluorine, nitrogen and aromatic ring addition. The compounds were tested in the pancreatic cell culture Mia-PaCa-2 and cell viability was assessed, with further IC50 calculation, stability and selectivity. Molecular docking was performed to evaluate the probable molecular target for 5b and in silico physicochemical properties were determined. Results: One molecule, named 5b, with two fluorine atoms inserted in the aromatic ring, exerted potent inhibitory activity on cell growth (IC50 = 1.39 µM), which was selective for pancreatic cells. Through molecular docking studies, the compound was found to be positioned in the active site of JAK3, indicating inhibition of such protein, which has a role in tumoral cell growth. Moreover, 5b was stable for 24 months and had physicochemical properties to permeate cell membranes, good oral absorption, and low potential to cause toxicity. Conclusions: These data suggest that 5b can be druggable and can be considered as a prototype for a new course of treatment in pancreatic cancer.

Turning Enzyme Models into Model Enzymes in a Substrate-Tailored, Desolvated Active Site

Turning Enzyme Models into Model Enzymes in a Substrate-Tailored, Desolvated Active Site

Multidimensional Engineering of Nanoconfined Catalysis: Frontiers in Carbon-Based Energy Conversion and Utilization

Amid global efforts toward carbon neutrality, nanoconfined catalysis has emerged as a transformative strategy to address energy transition challenges through precise regulation of catalytic microenvironments. This review systematically examines recent advancements in nanoconfined catalytic systems for carbon-based energy conversion (CO2, CH4, etc.), highlighting their unique capability to modulate electronic structures and reaction pathways via quantum confinement and interfacial effects. By categorizing their architectures into dimension-oriented frameworks (1D nanotube channels, 2D layered interfaces, 3D core-shell structures, and heterointerfaces), we reveal how geometric constraints synergize with mass/electron transfer dynamics to enhance selectivity and stability. Critical optimization strategies—including heteroatom doping to optimize active site coordination, defect engineering to lower energy barriers, and surface modification to tailor local microenvironments—are analyzed to elucidate their roles in stabilizing metastable intermediates and suppressing catalyst deactivation. We further emphasize the integration of machine learning, in situ characterization, and modular design as essential pathways to establish structure–activity correlations and accelerate industrial implementation. This work provides a multidimensional perspective bridging fundamental mechanisms with practical applications to advance carbon-neutral energy systems.

Discovering the Cholinesterase Inhibitory Potential of Thiosemicarbazone Derivatives through In vitro, Molecular Docking, Kinetics, and Dynamics Studies.

The current study explored the cholinesterase inhibitory activities of some thiosemicarbazone derivatives bearing 2,4-dichloro phenylacetic acid scaffold. This study aimed to screen the synthesized derivatives for their in vitro acetylcholine and butyrylcholinesterase inhibition. These compounds were synthesized by refluxing 2,4-dichloro phenylacetic acid with sulfuric acid in ethanol to get the ester, which was further refluxed with thiosemicarbazide in ethanol to get the desired compound (2). Different benzaldehydes were treated with compound (2) in ethanol having a catalytic amount of acetic acid to get thiosemicarbazones. In the series, seven compounds, including compounds 2c, 2a, 2b, 2d, 2g, 2e, and 2f, displayed excellent acetylcholinesterase inhibition activities in the range of IC50 values from 41.51 ± 3.88 to 95.48 ± 0.70 μM, surpassing than the standard galantamine (IC50 = 104.5 ± 1.20 μM). Also, compounds 2a, 2g, 2h, 2f, 2b, and 2d with IC50 values ranging from 64.47 ± 2.74 to 80.62 ± 0.73 μM exhibited potent inhibition against butyrylcholinesterase enzyme, being similar to the standard galantamine (IC50 = 156.8 ± 1.50 μM). The molecular docking investigation was performed to assess the binding affinity of the compounds with the active site of the enzyme. These compounds, along with the docked complexes, specifically AChE-compound 2a and BuChE-compound 2g, were chosen and subjected to 100-nanosecond molecular dynamics simulations. The simulations demonstrated strong stability of the ligands within the active pockets of AChE and BuChE enzymes. These derivatives exhibited superior acetylcholinesterase and butyrylcholinesterase inhibitory activities compared to galantamine, with molecular docking and dynamic simulations confirming their strong binding affinity with the active sites of the enzymes.

Understanding the active site structures and achieving catalytic activity tuning of atomically dispersed FeN4 sites for oxygen reduction reaction.

Atomicallydispersed Fe-N-C catalysts with high oxygen reduction reaction (ORR) activity have attracted great attention since the last decade. Due to its comparable ORR activity and low material cost, it is a promising platinum-group metal (PGM) free catalyst that can replace the commercialized Pt/C materials; furthermore, it can facilitate the efficiency of the fuel cell technologies and mitigate our dependence on fossil fuels. Great advancements have been made to experimentally optimize the synthesis approach of the Fe-N-C catalysts, enhance the ORR activity, and improve the catalyst stability. Similarly, recent theoretical studies also provide enriched understanding of the active site structures, properties, and reaction mechanisms. In this review, discussions are made upon utilizing combined experimental and computational spectroscopy to reveal the active site structures, employing mechanistic studies to investigate reaction thermodynamics and kinetics, as well as developing scaling relationships to assist the design and development of future PGM free catalyst materials. Furthermore, recent advances in studying Fe-N-C catalysts utilizing electrified surface and explicit solvation models are discussed. Not only can these aspects improve the accuracy of theoretical simulation and predictions but also deepen the understanding of the catalyst properties and reaction mechanisms under the effect of surface charges and solvent molecules.

Ketene Conversion Chemistry within Mordenite Zeolite: Pore-Size-Dependent Reaction Mechanism, Product Selectivity, and Catalytic Activity.

The oxide-zeolite bifunctional catalyst for ketene-bridged syngas conversion has gained great attention for addressing the selectivity challenge in light olefin production, where zeolite dominates the ketene conversion selectivity. However, the atomic-level mechanism underlying ketene-to-light olefin conversion within zeolite remains unclear. Herein, we focus on mordenite (MOR) zeolite and perform systematic first-principles calculations combined with microkinetic simulations to elucidate pore-type-dependent reaction networks for ketene-to-light olefin conversion. Our microkinetic results reveal that ketene conversion within MOR follows an autocatalytic process initiated by the Brønsted acid site, involving the generation and subsequent catalysis of reactive intermediates. Time-dependent dynamic evolution simulation shows that within the 12-membered-ring (12MR) pore, a thermodynamically stable five-membered-ring carbocation (FMR-CH3+) self-evolves and acts as the active center to convert CH2CO to multihydrocarbons. Instead, in the 8-membered-ring side pocket (8MR), direct CH3+ formation occurs via acetyl carbocation (CH3CO+) decarbonylation, inducing CH2CO conversion with exclusive ethylene selectivity. The distinct reaction mechanisms and product selectivities are attributed to the thermodynamic and kinetic constraints of cyclic/long-chain intermediate formation imposed by the smaller 8MR pore. Despite its higher free energy barrier, 8MR is identified as the key active site for light olefin formation due to its lower dependence on ketene pressure. We also highlight the critical factors influencing both the selectivity and activity of light olefin formation, offering valuable insights for the optimization of MOR catalysts. This study provides a quantitative mechanistic understanding of ketene conversion, emphasizing the role of pore structure in shaping catalytic activity and product selectivity, which may facilitate the design of efficient zeolite-based catalysts.