H-bond Acceptor Research Articles

Development of Benzimidazole Anticancer Leads for EGFR Inhibition by 3D-QSAR Based Virtual Screening, Molecular Docking, Molecular Simulation and Drug Likeness Study

Background: Breast cancer is the most common cancer in women. Tyrosine kinase inhibitors were developed to treat breast cancer. EGFR/ErbB1 inhibition has proved to be a promising target in breast carcinoma therapy. Drugs with benzimidazole nucleus have been approved by the FDA for cancer treatment. Objective: To design and develop benzimidazole anticancer small molecules for EGFR inhibition for the treatment of breast cancer. Methods: By 3D-QSAR-based virtual screening, molecular docking, molecular simulation and drug likeness study. Results: In this research, a 3D-QSAR pharmacophore was generated with four salient features. Namely H-bond acceptor (HBA), two ring aromatic (RA) and hydrophobic (HY) features. Its correlation- coefficient (r) is 0.8412, RMSD of 0 .96 and with 32.84 bits cost difference value. With virtual screening, 4 top hits were identified. Novel benzimidazole derivatives were designed (1a-ll) by using the features of hit molecules and the pharmacophore. The novel designed small molecules that were druggable as they passed the Lipinski and Veber rule. Novel ligands and EGFR protein interaction were good. 1a and 1i were found to be the best-designed molecules. They had -8.6 Kcal/mol and -8.4 Kcal/mol docking interaction energy, respectively, whereas Compound 4 (reference) scored -7.4 Kcal/mol. Both these molecules were stable inside the binding pocket of the EGFR protein. The molecular dynamic simulation study revealed that 1a attained equilibrium at 0.15nm. Conclusion: In silicon novel benzimidazole small molecules were designed and developed as EGFR inhibitors to treat breast cancer.

Competition between C-H⋯S and S-H⋯Cl H-bonds in a CHCl3-H2S complex: a combined matrix isolation IR spectroscopic and quantum chemical investigation.

H-bonded complexes between CHCl3 and H2S have been studied in a cold and inert argon matrix using IR spectroscopy. Both molecules were found to act as both a H-bond donor and acceptor, resulting in two different conformers. The more stable one (binding energy 3.25 kcal mol-1) was bound by a C-H⋯S H-bond, while the less stable one (1.90 kcal mol-1) by a S-H⋯Cl H-bond. The H-bonded complex formation has been confirmed by monitoring the spectral changes in νC-H and νS-H fundamental vibrations. The νC-H mode exhibited red shifts by 22.7 cm-1 upon C-H⋯S H-bond formation, while the formation of a S-H⋯Cl H-bond resulted in 24.2 and 25.4 cm-1 red shifts in the νS-H modes. The barrier for conversion of the less stable conformer to the more stable one was found to be 0.6 kcal mol-1. The rigid matrix environment prevented any detectable population transfer that required significant relative movement of the monomeric moieties. Dispersion interaction was found to significantly contribute to the overall stabilization of both conformers, more so for the S-H⋯Cl H-bonded one.

Unlocking Therapeutic Potential: Molecular Docking Insights into Aurora Kinase A Inhibitors Patented and Published from 2011-2020 for Innovative Anticancer Drug Design

Background: Enzymes belonging to the kinase family have been extensively implicated in cancer. Aurora A (AURKA) is crucial in regulating the cell cycle. AURKA's significant role in the formation of abnormal mitotic spindles and the failure of cytokinesis positions it as a promising target for anticancer treatments. Notably, AURKA is observed to be overexpressed in various cancer types, making its inhibition a compelling strategy for the development of anticancer agents. Objective: In this study, we set out to investigate a novel de novo design strategy aimed at developing and optimizing potent inhibitors for Aurora Kinase A. Given Aurora Kinase A's critical role in cell cycle regulation and its overexpression in various cancers, it presents a promising target for therapeutic intervention. Our goal was to create a new library of compounds, building on existing inhibitors known for their selectivity and potency against Aurora Kinase A. By making strategic modifications to these lead molecules, we aimed to improve their binding affinity and inhibitory effectiveness. This research was focused on identifying and refining compounds with enhanced drug-like properties and robust inhibitory potential, contributing to the advancement of effective anticancer therapies. Methods: A compound library based on known inhibitors having Aurora Kinase A selectivity and IC50 value in the nanomolar range was designed by modification in the lead molecules identified by analyzing the binding mode of the molecules in the catalytic site of the enzyme. A molecular docking study was performed in GOLD 2020. Drug-likeness ADME parameters (molecular weight, H-bond acceptors, H-bond donors, LogP, and the number of rotatable bonds) of designed molecules were calculated using SwissADME, pkCSM, and ProToxII web servers. Results: The docking study, utilizing GOLD 2020 software on Aurora Kinase A (PDB: 3W2C), successfully identified inhibitors that hindered the enzyme's activity by occupying its catalytic site. This inhibition mechanism, consistent across all cases, involves crucial interactions with residues such as Ala213, Asp274, and Phe144. A detailed analysis of the compounds guided the design of new analogs, aiming to enhance the lead compound's affinity for the receptor. Subsequent derivatization of M1 and M15 resulted in molecules (M1_46, M1_49, M1_50, M15_21, M15_14, and M15_43) showing a notable 10-15% increase in the Chemscore fitness scoring function compared to their parent molecules. This improvement correlated with a rise in the number of hydrogen bond interactions in the complexes, guiding further development. Conclusion: This computational assessment lays a foundation for further in-vitro and in-vivo studies in drug development, suggesting these derivatives as promising candidates for cancer treatment.

In silico molecular docking and molecular dynamic simulation of agarwood compounds with molecular targets of Alzheimer’s disease

Background Alzheimer’s disease (AD) is a neurological condition that primarily affects older people. Currently available AD drugs are associated with side effects and there is a need to develop natural drugs from plants. Aquilaria is as an endangered medicinal plant genus (commonly called agarwood plants) and various products of Aquilaria plant spp. including resinous heartwood, leaves, bark, and stem have been widely used in various traditional medicine systems. Research on agarwood plants is sparse and only a few previous studies demonstrated their neuroprotective properties in vitro. Owing to the presence of a plethora of secondary metabolites in agarwood plants, it is imperative not only to protect these plants but also evaluate the bioactivity of agarwood phytochemicals. Methods This study used Molsoft tools to predict the physicochemical properties of agarwood ligands, including the number of H-bond donors and acceptors, polar surface area, lipophilicity, solubility, and the molecular polar surface area and volume of agarwood ligands. Additionally, ADMET (absorption, digestion, metabolism, excretion, and toxicity) properties were predicted using ADMETlab 2.0. Computational methods such as AutoDock Vina and molecular dynamic (MD) simulations were employed for the docking of 41 selected agarwood compounds with AD-related molecular targets. Results and Conclusion According to docking data, three compounds aquilarisin (ASN), aquilarisinin (ANN), aquilarixanthone (AXN) showed highest binding affinity to selected AD targets compared to their known inhibitors. MD simulation studies revealed that, selected agarwood compounds’ protein-ligand complexes showed remarkable structural stability throughout 100ns simulation. The agarwood chemicals aquilarisin, aquilarisinin, aquilarixanthone, pillion (PLN), and agarotetrol (AGT) are consequently suggested as some of the found hits against AD targets, however, additional experimental validation is required to establish their effectiveness.

Synchronous Modulation of H-bond Interaction and Steric Hindrance via Bio-molecular Additive Screening in Zn Batteries.

In addressing challenges such as side reaction and dendrite formation, electrolyte modification with bio-molecule sugar species has emerged as a promising avenue for Zn anode stabilization. Nevertheless, considering the structural variability of sugar, a comprehensive screening strategy is meaningful yet remains elusive. Herein, we report the usage of sugar additives as a representative of bio-molecules to develop a screening descriptor based on the modulation of the hydrogen bond component and electron transfer kinetics. It is found that xylo-oligosaccharide (Xos) with the highest H-bond acceptor ratio enables efficient water binding, affording stable Zn/electrolyte interphase to alleviate hydrogen evolution. Meanwhile, sluggish reduction originated from the steric hindrance of Xos contributes to optimized Zn deposition. With such a selected additive in hand, the Zn||ZnVO full cells demonstrate durable operation. This study is anticipated to provide a rational guidance in sugar additive selection for aqueous Zn batteries.

Diverse Self-Assembled Molecular Architectures Promoted by C-H···O and C-H···Cl Hydrogen Bonds in a Triad of α-Diketone, α-Ketoimine, and an Imidorhenium Complex: A Unified Analysis Based on XRD, NEDA, SAPT, QTAIM, and IBSI Studies.

X-ray structural elucidation, supramolecular self-assembly, and energetics of existential noncovalent interactions for a triad comprising α-diketone, α-ketoimine, and an imidorhenium complex are highlighted in this report. Molecular packing reveals a self-assembled 2D network stabilized by the C-H···O H-bonds for the α-diketone (benzil), and the first structural report of Brown and Sadanaga stressing on the prevalence of only the van der Waals forces seems to be an oversimplified conjecture. In the α-ketoimine, the imine nitrogen atom undergoes intramolecular N···H interaction to render itself inert toward intermolecular C-H···N interaction and exhibits two types of C-H···O H-bonds in consequence to generate a self-assembled 2D molecular architecture. The imidorhenium complex features a self-aggregated 3D packing engendered by the interplay of C-H···Cl H-bonds along with the ancillary C-H···π, C···C, and C···Cl contacts. To the best of our knowledge, in rhenium chemistry, this imidorhenium complex unravels the first example of self-associated 3D molecular packing constructed by the directional hydrogen bonds of C-H···Cl type. The presence of characteristic supramolecular synthons, viz., R2 2(12), R2 2(16), and R2 2(14), in the α-diketone, α-ketoimine, and imidorhenium complex, respectively, has prompted us to delve into the energetics of noncovalent interactions. Symmetry-adapted perturbation theory analysis has authenticated a stability order: R2 2(14) > R2 2(12) > R2 2(16) based on the interaction energy values of -25.97, -9.93, and -4.98 kcal/mol, respectively. The respective average contributions of the long-range dispersion, electrostatic, and induction forces are 58.5, 32.8, and 8.7%, respectively, for the intermolecular C-H···O interactions. The C-H···Cl interactions experience comparable contribution from the dispersion force (57.9% on average), although the electrostatic and induction forces contribute much less, 28.0 and 14.1%, respectively, on average. The natural energy decomposition analysis has further attested that the short-range, interfragment charge transfer occurring via the lp(O/Cl) → σ*(C-H) routes contributes 17-25% of the total attractive force for the C-H···O and C-H···Cl interactions. Quantum theory of atoms in molecules analysis unfolds a first-order exponential decay relation (y = 8.1043e -x/0.4095) between the electron density at the bond critical point and the distance of noncovalent interactions. The distances of noncovalent interactions in the lattices are internally governed by the individual packing patterns rather than the chemical nature of the H-bond donors and acceptors. Intrinsic bond strength index analysis shows promise to correlate the electron density at BCP with the SAPT-derived interaction energy for the noncovalent interactions. Two factors: (i) nearly half the HOMO-LUMO energy difference for the imidorhenium complex (∼30 kcal/mol) compared to the organics, and (ii) ∼60% localization of HOMO over the mer-ReCl3 moiety clearly indicate an enhanced polarizability of the complex facilitating the growth of weak C-H···Cl H-bonds.

Cocrystal screening of benznidazole based on electronic transition, molecular reactivity, hydrogen bonding, and stability.

Screening of cocrystals of active pharmaceutical ingredients is important in the development of pharmaceutical compounds because it improves bioavailability, stability, solubility, and many other physicochemical properties. In this work, quantum chemical calculations were utilized for the computational evaluation of the cocrystal screening of benznidazole (BZN) API via hydrogen bonding with four coformers (maleic acid, malonic acid, oxalic acid, and salicylic acid), and they contain carboxylic groups. The nitrogen of the imidazole ring in benznidazole and the carboxylic group of the coformer form a hetero-synthon connected by a strong hydrogen bond. The strength of the hydrogen bonding interaction O-H…N was measured using various tools. It was found that in comparison to BZN cocrystals with malonic acid, oxalic acid, and salicylic acid, the O-H…N interaction in the BZN-maleic acid cocrystal had higher interaction energy, indicating it had stronger hydrogen bonding. The strength of the hydrogen bond O-H…N for synthons was discovered to be more beneficial than the C-H…O interaction, as confirmed by ESP analysis. The BZN-salicylic acid cocrystal was found to be more reactive and polarizable, whereas the BZN-malonic acid cocrystal was more stable. Cocrystals of benznidazole exhibited better physicochemical characteristics than API benznidazole, as indicated by electron transition properties between the most significant orbitals. The computational evaluation for the screening of benznidazole cocrystals was performed in Gaussian 16 software using density functional theory (DFT) with the hybrid functional B3LYP and the basis set 6-311 + + G(d,p). The UV-Vis absorption spectrum in solvent water was analyzed using the TD-DFT/6-311 + + G(d,p) method to determine the influence of the solvent in cocrystals using a polarizable continuum model. The strength of the hydrogen bonding interactions O-H…N in each of those mentioned cocrystals was used to screen the cocrystals using tools such as thermodynamic probability, ESP analysis, QTAIM analysis, and NBO analysis. The pairing energy of interaction was measured by determining H-bond donor ( ) and H-bond acceptor ) parameters for hydrogen bonds from maxima and minima on the ESP surface. GaussView 06 software was used to create, visualize, and plot the optimized structure of the cocrystal and HOMO-LUMO orbitals. The AIMALL (10.05.04) software package generated the molecular graph for intra- and intermolecular interactions. The RDG-scatter plot, MEP map, and ELF plot were rendered from Multiwfn 8.0 and VMD 1.9.1 software.

Thermodynamics of Anion Binding by (Thio)ureido-calix[4]arene Derivatives in Acetonitrile.

In this work, we developed (thio)ureido-calix[4]arene derivatives and thoroughly explored their anion-binding properties in acetonitrile. A series of anions, including important inorganic ones (Cl-, HSO4 -, H2PO4 -, and HP2O7 3-) and several ever-present carboxylates (acetate, benzoate, and fumarate), were studied. All systems were investigated by several methods (NMR, ITC, and UV) used in a synergistic fashion, providing their comprehensive thermodynamic description. Acidities of the receptors were determined prior to the anion-binding studies and considered in the data-handling procedures. Complexes of various stoichiometries were detected and the driving force for their formation elucidated. The correlation of the anion structural features and H-bond acceptor properties with the stoichiometries and complexation thermodynamics parameters was rationalized. Generally, stability of the complexes followed the trend defined by the basicity of anions. Thiourea and urea analogues exhibited similar affinities for anion binding except for the H2PO4 - and HP2O7 3-, which interacted with the thiourea analogue more strongly. The hosts endowed with 4 (thio)urea groups formed species containing two receptor molecules bridged by a fumarate or hydrogen pyrophosphate anion. Thermodynamic information provided in this work is applicable in further design of supramolecular systems, whereas the presented approach to data handling will aid researchers when dealing with multiple coexisting equilibria.

Development of Abraham model correlations for predicting the solubility of crystalline organic compounds and inorganic gases in ethyl formate

ABSTRACT Abraham model correlations are derived for predicting the solubility of crystalline organic compounds and inorganic gases dissolved in ethyl formate based on published experimental data gathered from the chemical literature. The mathematical expressions presented in the current study described the observed solubility data to within an overall standard deviation of 0.12 log units. Comparison of the Abraham model expressions for ethyl formate versus our recently published equations for ethyl acetate reveals that of the two organic solvents, ethyl acetate exhibits a better H-bond acceptor character, while ethyl formate engages in the stronger dipolar interactions with neighbouring solute molecules.

Amine-functionalized soy protein/graphene oxide aerogel for efficient removal of multiple sugar-derived contaminants (SDCs): Full life cycle exploration and interaction simulation

Sugar-derived contaminants (SDCs) pose significant environmental hazards and safety concerns, emerging as urgent issue. Using amine-modified soy protein (SPI) and graphene oxide (GO), an environment-friendly aerogel (PSPI/PGO) was synthesized to efficiently remove multiple SDCs. The equilibrium adsorption capacities of PSPI/PGO for melanoidins, caramels, and saccharin were 1124.2, 291.1, and 399.3 mg/g, respectively, surpassing those of previously proposed materials. A series of characterizations and experiments demonstrated that the porous PSPI/PGO exhibited high hydrophilicity, nontoxicity, excellent thermal stability, and sustainable capture properties. Emerging dynamic models (i.e., AOAS, EXT-INT, and LF-PC-AS) and multiple quantum chemical theory calculations (ESPL, ALIE, FMO, IGMH, and HSA) further revealed the capture of each SDC onto PSPI/PGO was driven predominantly by charge interactions, followed by H-bonding and intermolecular interactions. PSPI/PGO acts as an H-bonding acceptor in a diverse range of uptake processes for each SDC. The applicability of PSPI/PGO for treating real wastewater has been validated. The full lifecycle exploration of PSPI/PGO (including soil burial degradation tests, wastewater treatment, and garlic hydroponic experiments using depleted PSPI/PGO) underscores its considerable biocompatibility and potential for industrial applications.

A Dual CQD-Catalysis and H-Bond Acceptor for Controlling Product Selectivity and Regioselectivity in Symmetric/Unsymmetric Azoxy Arenes.

Azoxy arenes are valuable compounds in different areas of chemistry, such as organic chemistry, medicinal chemistry, and natural product chemistry. Despite their value, the regioselective synthesis of unsymmetric azoxybenzenes has remained a real challenge in the field. Herein, the product selectivity in oxidative homocoupling of anilines into symmetric azoxybenzenes was first achieved by an asparagine-functionalized CQD catalyst. Subsequently, in the cross-coupling of anilines into the unsymmetric azoxybenzenes via an ortho H-bond acceptor (HBA) on one of the coupling anilines, the regioselectivity was effectively controlled. It was demonstrated that ortho-HBA could mechanistically establish a six-membered intramolecular hydrogen-bonded ring on an N,N'-dihydroxy intermediate. The formed hydrogen bond makes the nearby nitrogen eminently suitable for the slow dehydration step. As a result, the functional oxygen of the azoxy compound is placed far from the HBA. The o-HBA mechanism also controls the regioselectivity ratio in which 1:0 (with an intramolecular H-bonded hexagonal ring), 2:1 (with an intramolecular H-bonded pentagonal ring), and 1:1 (without an ortho-HBA) isomeric mixtures could be achieved. The HBA mechanism was exploited by different substituted anilines, and various unsymmetric azoxybenzenes were synthesized. Finally, with the aid of mechanistic studies, a plausible mechanism for the reaction was proposed.

Molecular Bridging Induced Anti-salting-out Effect Enabling High Ionic Conductive ZnSO4-based Hydrogel for Quasi-solid-state Zinc Ion Batteries.

Hydrogel electrolytes (HEs) hold great promise in tackling severe issues emerging in aqueous zinc-ion batteries, but the prevalent salting-out effect of kosmotropic salt causes low ionic conductivity and electrochemical instability. Herein, a subtle molecular bridging strategy is proposed to enhance the compatibility between PVA and ZnSO4 from the perspective of hydrogen-bonding microenvironment re-construction. By introducing urea containing both an H-bond acceptor and donor, the broken H-bonds between PVA and H2O, initiated by the SO42--driven H2O polarization, could be re-united via intense intermolecular hydrogen bonds, thus leading to greatly increased carrying capacity of ZnSO4. The urea-modified PVA-ZnSO4 HEs featuring a high ionic conductivity up to 31.2 mS cm-1 successfully solves the sluggish ionic transport dilemma at the solid-solid interface. Moreover, an organic solid-electrolyte-interphase can be derived from the in-situ electro-polymerization of urea to prohibit H2O-involved side reactions, thereby prominently improving the reversibility of Zn chemistry. Consequently, Zn anodes witness an impressive lifespan extension from 50 h to 2200 h at 0.1 mA cm-2 while the Zn-I2 full battery maintains a remarkable Coulombic efficiency (>99.7%) even after 8000 cycles. The anti-salting-out strategy proposed in this work provides an insightful concept for addressing the phase separation issue of functional HEs.

Spectrophotometric Determination of Cobalt(II) by Natural Deep Eutectic Solvent (NADES) Air-Assisted Dispersive Liquid-Liquid Microextraction (AA-DLLME)

Cobalt is beneficial for human activity but has adverse effects when discharged in large quantities. Therefore, its precise and accurate quantification in samples is of importance. Here, a natural deep eutectic solvent (NADES), composed of camphor (H-bond acceptor) and menthol (H-bond donor), has been used for the preconcentration of Co(II) from water samples before determination by a spectrophotometer at 398 nm. The 8-hydroxyquinoline-Co(II) complex was transferred to the NADES using air-assisted dispersive liquid-liquid microextraction (AA-DLLME). The extraction efficiency was enhanced through fine tuning of various parameters, including pH, NADES volume, and quantity of dispersant. Similarly, the centrifugation rate and time, quantity of the complexing agent, matrix effects, and salt concentration were also evaluated. Under the optimized conditions, an enrichment factor of 37.5 and a preconcentration factor of 37.5 were obtained. The limits of detection (LOD) and quantification (LOQ) were 0.44 µg/L and 1.47 µg/L, respectively. For seven replicates of 50 µg/L Co(II), the relative standard deviation was 3.2%. The developed method was employed for the determination of Co(II) in water samples, with quantitative recovery values from 94.5 to 98.5%.

Single-Crystal Structure Analysis of Dicarboxamides: Impact of Heteroatoms on Hydrogen Bonding of Carboxamide Groups

This research examines how heteroatoms in a six- or five-membered pyridine, thiophene or furan ring spacer between two carboxamide groups influence the hydrogen bonding for advancements in supramolecular chemistry and drug development. The solvent-free crystal structures of 3,5-pyridinedicarboxamide (PDC), 2,5-thiophenedicarboxamide (TDC) and 2,5-furandicarboxamide (FDC-subl, crystallized by sublimation), and the monohydrate structure of FDC-solv (crystallized from methanol) are described with the hydrogen-bonding analyzed by the Etter graph-set notation. The carbon atoms of the amide groups form an angle of 121° in PDC, 151° in TDC, 137° in FDC-solv and 135° in FDC-subl with the ring centroid. Only in the structure of PDC does the heteroatom act as an H-bond acceptor as part of a C11(6) chain. In TDC and FDC, the heteroatoms do not interact with the amide -NH2 groups.

Water orientation on platinum surfaces controlled by step sites.

In this work, the adsorption structure of deuterated water on the stepped platinum surface is studied under an ultra-high vacuum by using heterodyne-detected sum-frequency generation spectroscopy. On a pristine Pt(553), D2O molecules adsorbed at the step sites act as hydrogen bond (H-bond) donors to the adjacent terrace sites. This ensures the net D-down orientation at the terrace sites away from the steps. In particular, the pre-adsorption of oxygen atoms at the step sites significantly alters the D-down configuration. The oxygen pre-adsorption leads to a spontaneous dissociation of the post-adsorbed water molecules at the step to form hydroxyl (OD) species. Since the hydroxyl at the step acts as a strong H-bond acceptor, D2O at the terrace no longer maintains the D-down configuration and adopts flat-lying configurations, significantly reducing the number of D-down molecules at the terrace. Density-functional theoretical calculations support these pictures. This work demonstrates the critical role of steps in controlling the net orientation of the interfacial water and provides an important reference for future considerations of the reactions at electrochemical interfaces.

Direct evidence for a deprotonated lysine serving as a H-bond "acceptor" in a photoreceptor protein.

Deprotonation or suppression of the pKa of the amino group of a lysine sidechain is a widely recognized phenomenon whereby the sidechain amino group transiently can act as a nucleophile at the active site of enzymatic reactions. However, a deprotonated lysine and its molecular interactions have not been directly experimentally detected. Here, we demonstrate a deprotonated lysine stably serving as an "acceptor" in a H-bond between the photosensor protein RcaE and its chromophore. Signal splitting and trans-H-bond J coupling observed by NMR spectroscopy provide direct evidence that Lys261 is deprotonated and serves as a H-bond acceptor for the chromophore NH group. Quantum mechanical/molecular mechanical calculations also indicate that this H-bond exists stably. Interestingly, the sidechain amino group of the lysine can act as both donor and acceptor. The remarkable shift in the H-bond characteristics arises from a decrease in solvation, triggered by photoisomerization. Our results provide insights into the dual role of this lysine. This mechanism has broad implications for other biological reactions in which lysine plays a role.

Sustainable protein/polysaccharide aerogel for the simultaneous and efficient removal of multiple organic contaminants: Insights from DFT calculations and phenomenological mass–transfer modeling

Wastewater contains various organic contaminants that pose great hazards to human health and the environment. A protein/polysaccharide-derived aerogel, namely, ICMA, was developed as a high-performance adsorbent for the simultaneous and efficient removal of diverse contaminants from wastewater, including melanoidin (MLE), Congo red (CR), and diclofenac (DIC). Metal organic framework (UiO-66-NH2), as a regulatory factor, significantly improved the porosity and pore volume of the ICMA to enhance the capture performance of contaminants. The ICMA exhibited outstanding adsorption efficiency owing to the incorporation of ample polyamine functional groups and its well-developed pore structure, large porosity and pore volume, and remarkable heat resistance. The equilibrium capture capacities of the ICMA were 1364, 2031, and 539 mg/g for MLE, CR, and DIC, respectively, with corresponding removal efficiencies all exceeding 90%. Furthermore, the ICMA can capture cationic dyes through MLE/CR/DIC-bridging interactions. After five cycles, the used ICMA can still maintain a high contaminant removal rate/amount, demonstrating good reusability. The classic adsorption model showed that the capture of contaminants by the ICMA is a double-layered and heterogeneous adsorption orientation. A brand new LWAMTM model demonstrated that the adsorption mass–transfer process is jointly determined by the external mass conveyance, pore diffusion, and adsorption on the active site. Multiple characterizations indicated that the contaminant adsorption onto the ICMA was mainly facilitated by charge interactions, with H-bonds playing a secondary role. Quantum chemical theory simulations further provide insights into the atomic-level mechanisms involved in the capture of contaminants. Hirshfeld surface analysis revealed that the ICMA functions as both an H-bond acceptor and a donor during contaminant adsorption. Scale-up and upgrade adsorption were performed to treat actual/simulated wastewater, establishing the groundwork for the industrial implementation of the ICMA.

Elucidation of the stereochemical mechanism of cystathionine γ-lyase reveals how substrate specificity constrains catalysis.

Pyridoxal phosphate (PLP)-dependent enzymes play essential roles in metabolism and have found applications for organic synthesis and as enzyme therapeutics. The vinylglycine ketimine (VGK) subfamily hosts a growing set of enzymes that play diverse roles in primary and secondary metabolism. However, the molecular determinates of substrate specificity and the complex acid-base chemistry that enables VGK catalysis remain enigmatic. We use a recently discovered amino acid γ-lyase as a model system to probe catalysis in this enzyme family. We discovered that two stereochemically distinct proton transfer pathways occur. Combined kinetic and spectroscopic analysis revealed that progression through the catalytic cycle is correlated with the presence of an H-bond donor after Cγ of an amino acid substrate, suggesting substrate binding is kinetically coupled to a conformational change. High-resolution X-ray crystallography shows that cystathionine-γ-lyases generate an s-trans intermediate and that this geometry is likely conserved throughout the VGK family. An H-bond acceptor in the active site templates substrate binding but does so by pre-organizing substrates away from catalytically productive orientations. Mutagenesis eliminates this pre-organization, such that there is a relaxation of the substrate specificity, but an increase in k cat for diverse substrates. We exploit this information to perform preparative scale α,β,β-tri-deuteration of polar amino acids. Together, these data untangle a complex mode of substrate specificity and provide a foundation for the future study and applications of VGK enzymes.

Chiral Diselenophosphoric Acids for Ion Pair Catalysis: A Novel Approach to Enhance Both Proton Donating and Proton Accepting Properties.

The activation of poorly reactive substrates via strong chiral acids is a central topic in asymmetric ion pair catalysis these days. Despite highly successful scaffolds such as N-triflylphosphoramides, these catalysts either lack C2-symmetry or provide multiple H-bond acceptor sites, leading to lower ee values for certain reactions. We present BINOL-based diselenophosphoric acids (DSA) as an extremely promising alternative. Using an intertwined approach of synthesis and NMR studies, we developed a synthetic approach to DSA with up to 98 % NMR yield. The obtained acids provide both very high proton donor and proton acceptor properties, a bifunctionality, which is key to catalytic applications. Indeed, first reactivity test proved the much higher acidity of DSA and its ability to initiate Mukaiyama-Mannich reaction and protodesilylation of silyl ethers. Together with their C2-symmetry, the single donor and single acceptor situation, the decreased tendency of self-association, and the straightforward synthesis with potential 3,3'-substitution, the DSA provide all features ideal for the further development of ion pair catalysis.

Influence of cholesterol on hydrogen-bond dynamics of water molecules in lipid-bilayer systems at varying temperatures.

Cholesterol (Chol) plays a crucial role in shaping the intricate physicochemical attributes of biomembranes, exerting a considerable influence on water molecules proximal to the membrane interface. In this study, we conducted molecular dynamics simulations on the bilayers of two lipid species, dipalmitoylphosphatidylcholine (DPPC) and palmitoyl sphingomyelin; they are distinct with respect to the structures of the hydrogen-bond (H-bond) acceptors. Our investigation focuses on the dynamic properties and H-bonds of water molecules in the lipid-membrane systems, with a particular emphasis on the influence of Chol at varying temperatures. Notably, in the gel phase at 303K, the presence of Chol extends the lifetimes of H-bonds of the oxygen atoms acting as H-bond acceptors within DPPC with water molecules by a factor of 1.5-2.5. In the liquid-crystalline phase at 323K, on the other hand, H-bonding dynamics with lipid membranes remain largely unaffected by Chol. This observed shift in H-bonding states serves as a crucial key to unraveling the subtle control mechanisms governing water dynamics in lipid-membrane systems.