H-bond Acceptor Research Articles

Phytochemdb: a platform for virtual screening and computer-aided drug designing.

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed ‘phytochemdb’, a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood–Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. ‘phytochemdb’ is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. ‘phytochemdb’ is available for free at https://phytochemdb.com/.

Prototropic behavior of naphthalene derived probes in deep eutectic solvents

Deep eutectic solvents (DESs) have garnered widespread acceptance as novel and biodegradable substitutes to the volatile organic solvents and ionic liquids in both biological and chemical sciences. The prototropic equilibria of fluorescent probes is known to be largely controlled by its surrounding milieu. The prototropic behavior of four naphthalene derivatives: 1-naphthol, 2-naphthol, 1-naphthylamine, and 1,8-bis(dimethylamino)naphthalene (the proton sponge) is investigated within five different DESs constituted of choline chloride (ChCl) as a common H-bond acceptor (HBA) with five different H-bond donors (HBDs). UV–vis molecular absorption and steady-state fluorescence spectroscopies along with time-resolved fluorescence measurements are used to investigate the ground-state and excited-state prototropic behavior of these four probes dissolved in the five DESs. For 2-naphthol, neutral form is the only absorbing and emitting form observed in all the investigated DESs. In the ground-state, 1-naphthol is predominantly present in its neutral form within all the investigated DESs. However, both neutral and anionic forms of 1-naphthol are supported in the excited-state of ChCl:Urea DES whereas neutral form remains the preferred form in other DESs. In all the investigated DESs, the neutral form of 1-naphthylamine is the only prominent form in both ground- and excited-state. The cationic form of 1,8-bis(dimethylamino)naphthalene remains the dominant prototropic form in ground- as well as excited-state in all the investigated DESs upholding the high photo-basicity of this probe in DESs as well.

A Combined Approach of Pharmacophore Modeling, QSAR Study, Molecular Docking and In silico ADME/Tox Prediction of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one Analogs to Identify Potential Reverse Transcriptase Inhibitor: Anti-HIV Agents.

Reverse transcriptase is an important therapeutic target to treat AIDS caused by the Human Immunodeficiency Virus (HIV). Despite many effective anti-HIV drugs, reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In the present work, we have expedited the use of different computational modules and presented an easy, costeffective, and high throughput screening method to identify potential reverse transcriptase inhibitors. A congeneric series of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one analogs having anti-HIV activity were subjected to structure-based 2D, 3D QSAR, Pharmacophore Modeling, and Molecular Docking to elucidate the structural properties required for the design of potent HIV-RT inhibitors. Prediction of preliminary Pharmacokinetic and the Drug Likeliness profile was performed for these compounds by in silico ADME study. The 2D and 3D- QSAR models were developed by correlating two and three-dimensional descriptors with activity (pIC50) by sphere exclusion method and k-nearest neighbor molecular field analysis approach, respectively. The significant 2D- QSAR model developed by Partial Least Square is associated with the Sphere Exclusion method (PLS-SE), having r2 and q2 values 0.9509 and 0.8038, respectively. The 3D-QSAR model by Step Wise variable selection method (SW-kNN MFA) is more significant, which has a cross-validated squared correlation coefficient q2= 0.8509 and a non-crossvalidated correlation coefficient pred_r2= 0.8102. The pharmacophore hypothesis was developed, which comprised 5 features includes 3 aliphatic regions (Ala), 1 H-bond donor (HDr) and 1 H-bond acceptor (HAc). Docking studies of the selected inhibitors with the active site of reverse transcriptase enzyme showed hydrogen bond and π - π interaction with LYS-101, LYS-103, TYR- 181, TYR-188 and TRP-229 residues present at the active site. All the candidates with good bioavailability and ADMET drug likeliness properties. The results of the present work provide more useful information and important structural insights for the discovery, design of novel and potent reverse transcriptase inhibitors with high therapeutic windows in the future.

3D QSAR and pharmacophore studies on inhibitors of insuline like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) as potential anti-cancer agents

Insulin like growth factor receptor (IGF-1R) and Insulin receptor (IR) are widely accepted to play a prominent role in cancer drug discovery due to their well-established involvement in various stages of tumorigenesis. Previously, neutralization of IGF-1R via monoclonal antibodies was in focus, which failed because of compensatory activation of IR-A upon inhibition of IGF-1R. Recent studies have demonstrated high homology between IGF-IR and IR particularly in tyrosine kinase domain and targeting both receptors have produced efficient therapeutic approaches such as inhibition of cancer cell cycle proliferation. Herein, we have made an attempt to analyze the unique data set from different chemical classes, containing potent ATP competitors against tyrosine kinase domain. We performed the 2D, 3D quantitative structure–activity relationship (QSAR) studies on inhibitors of these receptors to predict useful pharmacophoric features. We have optimized virtual screening of structurally diverse data set of dual inhibitors of IGF-1R and IR. Based on QSAR studies, we predict potential novel clinical candidates with a demonstrated absorption, distribution, metabolism, elimination, and toxicology (ADMETox) track. We also demonstrated comprehensive analysis of co–crystal complexes along with their inhibitors and built 3D- GRid INdependent Descriptors (GRIND) model to obtain insightful features such as H-bond donors and acceptors, overall topology and Vander Waal volume (vdw_vol) which are found to be responsible for dual inhibition of receptors. These findings lead to further description that Tirofiban, Practolol, Edoxaban, Novobiocin have potential to perform dual inhibition of both targets. • Monoclonal antibodies to neutralise IGF-1R failed due to activation of IR upon IGF-1R inhibition leading. • The study focuses on ATP competitive ligands from different chemicals classes against tyrosine kinase using 2D and 3D QSAR. • Our study predicts Tirofiban, Practolol, Edoxaban and Novobiocin as potential novel candidates for dual inhibition. • We cross validated these ligands by building additional pharmacophores which confirmed the Mathew's correlation at 79%.

Screening ionic liquids for dissolving hemicellulose by COSMO-RS based on the selective model.

The utilization of biomass resources has attracted more and more attention due to the consumption of non-renewable resources. Compared with cellulose and lignin, hemicellulose has been less studied. Some ionic liquids (ILs) have been proved to be excellent solvents for lignocellulosic pretreatment. However, screening of more efficient ILs is difficult due to numerous possible ILs. Computational chemistry has been proved effective in solvent screening, but a precise model is indispensable. In this work, we focused on building several appropriate models and selected the most suitable one. According to the structure of hemicellulose, six hemicellulose models were constructed and the mid-dimer of the xylan chain hemicellulose (MDXC) model was proved to be the best compared with the reported experimental results. Based on the MDXC model, 1368 ILs were screened to evaluate their ability to dissolve hemicellulose by Conductor-like Screening Model for Real Solvents (COSMO-RS). The activity coefficient (γ), excess enthalpy (HE), and σ-profile indicated that the hydrogen-bond (H-bond) played a vital role in the dissolution of hemicellulose. Anions played a more critical role than cations, where small anions with H-bond acceptor groups could enhance the molecular interactions with hemicellulose. This work provided a thermodynamic understanding of hemicellulose and IL solvent systems. It highlights the importance of building appropriate solute models, which may be necessary to predict of the other thermodynamic properties in the future.

Lead optimization, pharmacophore development and scaffold design of protein kinase CK2 inhibitors as potential COVID-19 therapeutics

Therapeutic agents being designed against COVID-19 have targeted either the virus directly or the host cellular machinery. A particularly attractive host target is the ubiquitous and constitutively active serine-threonine kinase, Protein kinase CK2 (CK2). CK2 enhances viral protein synthesis by inhibiting the sequestration of host translational machinery as stress granules and assists in viral egression via association with the N-protein at filopodial protrusions of the infected cell. CK2 inhibitors such as Silmitasertib have been proposed as possible therapeutic candidates in COVID-19 infections. The present study aims to optimize Silmitasertib, develop pharmacophore models and design unique scaffolds to modulate CK2. The lead optimization phase involved the generation of compounds structurally similar to Silmitasertib via bioisostere replacement followed by a multi-stage docking approach to identify drug-like candidates. Molecular dynamics (MD) simulations were performed for two promising candidates (ZINC-43206125 and PC-57664175) to estimate their binding stability and interaction. Top scoring candidates from the lead optimization phase were utilized to build ligand-based pharmacophore models. These models were then merged with structure-based pharmacophores (e-pharmacophores) to build a hybrid hypothesis. This hybrid hypothesis was validated against a decoy set and used to screen a diverse kinase inhibitors library to identify favored chemical features in the retrieved actives. These chemical features include; an anion, an aromatic ring and an H-bond acceptor. Based on the knowledge of these features; de-novo scaffold design was carried out which identified phenindiones, carboxylated steroids, macrocycles and peptides as novel scaffolds with the potential to modulate CK2. Communicated by Ramaswamy H. Sarma

Separation of isopropyl ether and acetone using ionic liquids based on quantum chemistry calculation and liquid–liquid equilibrium

Selecting green and efficient extractive solvents are the inevitable requirement of sustainable development. Ionic liquids as green solvents are widely used in the separation of organic substance. In this manuscript, ionic liquids are used as extractive solvents to separate isopropyl ether-acetone system. The selected ionic liquids are 1-ethyl-3-methylimidazole dinitrile amine [EMIM][DCA], n-butyl-3-methylimidazole trifluoromethane sulfonate [BMIM][OTF], 1-ethyl-3-methylimidazole trifluoromethane sulfonate [EMIM][OTF]. Firstly, the relation between H-bonding donor and H-bonding acceptor is description by COSMO-SAC model based on the extraction mechanism. After that the experiments of liquid–liquid equilibrium are conducted at T = 298.15 K and P = 101.325 kPa, and the liquid–liquid equilibrium data are correlated by NRTL model. The results indicate that the model has a good correlation with the experimental results. Finally, the extraction mechanism is discussed at micro scale. The H-bonding interaction between ionic liquids and acetone, including total charge density, bond length, deformation charge density and interaction energy, is determined by quantum chemistry calculation. The quantum chemical calculation and experimental process provide theoretical guidance for the highly efficient separation of acetone - isopropyl ether binary system.

Isotope Effects on the Vaporization of Organic Compounds from an Aqueous Solution-Insight from Experiment and Computations.

An isotope fractionation analysis of organic groundwater pollutants can assess the remediation at contaminated sites yet needs to consider physical processes as potentially confounding factors. This study explores the predictability of water–air partitioning isotope effects from experiments and computational predictions for benzene and trimethylamine (both H-bond acceptors) as well as chloroform (H-bond donor). A small, but significant, isotope fractionation of different direction and magnitude was measured with ε = −0.12‰ ± 0.07‰ (benzene), εC = 0.49‰ ± 0.23‰ (triethylamine), and εH = 1.79‰ ± 0.54‰ (chloroform) demonstrating that effects do not correlate with expected hydrogen-bond functionalities. Computations revealed that the overall isotope effect arises from contributions of different nature and extent: a weakening of intramolecular vibrations in the condensed phase plus additional vibrational modes from a complexation with surrounding water molecules. Subtle changes in benzene contrast with a stronger coupling between intra- and intermolecular modes in the chloroform–water system and a very local vibrational response with few atoms involved in a specific mode of triethylamine. An energy decomposition analysis revealed that each system was affected differently by electrostatics and dispersion, where dispersion was dominant for benzene and electrostatics dominated for chloroform and triethylamine. Interestingly, overall stabilization patterns in all studied systems originated from contributions of dispersion rather than other energy terms.

3D-QSAR, molecular docking, DFT and ADMET studies on quinazoline derivatives to explore novel DHFR inhibitors

Resistance to folate antagonists is caused by mutations in the dihydrofolate reductase (DHFR) genes. These mutations affect the amino acids at positions 51, 59, 108 and 164 of DHFR, which appear to play a major role in malaria treatment failure. Therefore, the design of new drugs able to overcome the problem of antifolate drug resistance should receive urgent attention. In this study, a three-dimensional quantitative structure-activity relationship (3 D-QSAR) and molecular docking studies have been performed on antimalarial quinazoline derivatives. The CoMFA (Q2 = 0.63, R2 = 0.83 and = 0.70) and the CoMSIA (Q2 = 0.584, R2 = 0.816, and = 0.73) models show a good prediction of antimalarial activity. The reliability and robustness of the proposed models have been tested using several validation methods, which showed that the steric, electrostatic, hydrophobic and H-bond acceptor fields of the CoMSIA model play a key role in the prediction of antimalarial activity. Molecular docking studies reveal important interactions between two isomeric compounds (meta and para) and the DHFR receptor in its wild and mutant forms. The obtained outcomes of molecular docking studies have been validated using a new method based on visual inspection. The DFT study of the two isomeric compounds confirms clearly the trends of 3 D-QSAR and molecular docking for the design of new compounds. Moreover, the consistency between theoretical, 3 D-QSAR and molecular docking analysis provides guidance for the design of new drug candidates, which have been tested using ADMET properties and drug likeness analysis. Communicated by Ramaswamy H. Sarma

Sulfuric acid-mediated synthesis of 2,5-disubstituted 1,3,4-thiadiazole via intramolecular cyclization reaction from dithioesters: An approach to crystal structure prediction, DFT studies and Hirshfeld surface analysis

There is an immense need to discover novel methods that would make diversely functionalized molecules available through atom-economical and environmentally friendly reactions that minimize the use of organic solvents. An efficient and facile synthesis of 2, 5-disubstituted 1, 3, 4-thiadiazoles via intramolecular cyclization from dithioesters and benzoic acid in presence of H2SO4 has been developed using dithioesters. The synthesized compound was characterized and confirmed by NMR analysis and single-crystal X-ray diffraction studies. The geometry (bond lengths and bond angles), and molecular properties were estimated by means of the density functional theory (DFT) at B3LYP/6–31 G level of theory with no symmetry constraints. Frontier molecular orbital (HOMO and LUMO) was drawn using the optimized structures which elucidates the charge transfer collaboration and chemical stability of the compound. Good correlation coefficients were found (R2 = 0.9629 and 0.9176,) between the experimental bond length and bond angles and theoretical values. The Hirshfeld surface (HS) analysis showed that oxygen and nitrogen atoms of the 5 h compound may act as H-bond acceptors, some H-bonds contacts are expected to be shown as red spots on the HS of the molecule.

Ionic liquids screening for lignin dissolution: COSMO-RS simulations and experimental characterization

As the second most abundant terrestrial polymer, lignin has emerged as a major sustainable source for the production of fuels, chemicals, and materials. However, efficient screening of solvents for lignin dissolving faces great challenges. In this work, COSMO-RS was used to screen 3886 ionic liquids (ILs) composed of 58 cations and 67 anions, to find out the most effective ones for lignin dissolving by considering the critical items of logarithmic infinite dilution activity coefficient (lnγ∞) and σ-profiles. The substantial improvement of lignin dissolution was achieved in [PMpyrr][OAc] IL by both simulations and experiments validations. Moreover, it was found that the anions dominate the dissolution process and the strongly polar anions exhibit better dissolution ability. Furthermore, the underlying mechanism originated from the hydrogen bond (H-bond) between ILs and lignin was also revealed and systemically analyzed from donor and acceptor ability, indicating that high lignin solubility is reached in the ILs with stronger ability to form H-bond acceptors. This work leads to possible ways toward developing more selective and efficient lignin dissolution methods based on solvent properties.

Irradiation-Wavelength Directing Circularly Polarized Luminescence in Self-Organized Helical Superstructures Enabled by Hydrogen-Bonded Chiral Fluorescent Molecular Switches.

Two light-driven chiral fluorescent molecular switches, (R,S,R)-switch 1 and (R,S,R)-switch 2, are prepared by means of hydrogen-bonded (H-bonded) assembly of a photoresponsive (S) chiral fluorescent molecule, respectively with a cyano substitution at different positions as an H-bond acceptor and an opposite (R) chiral molecule as an H-bond donor. The resulting two switches exhibit tunable and reversible Z/E photoisomerization irradiated with 450 nm blue and 365 nm UV light. When doped into an achiral liquid crystal, both switches are found to be able to form a CPL tunable luminescent helical superstructure. In contrast to the tunable CPL characteristics of the system incorporating switch 2, exposure of the system incorporating switch 1 to 365 nm and 450 nm radiation can lead to controllable different photostationary CPL behavior, including switching-off and polarization inversion. In addition, optical information coding is demonstrated using the system containing switch 1.

Ultra-Stable Metal–Organic Framework with Concurrent High Proton Conductivity and Fluorescence Sensing for Nitrobenzene

Luminescent metal–organic frameworks (MOFs) coupled with proton conduction offer wide applications in clean energy and luminescence sensors. High stability and remarkable proton conductivity and sensing are requisites for practical applications. Specifically, high thermal and chemical stabilities under harsh conditions are important but challenging to achieve. Herein, an ultra-stable Cu(I)-tetrazolate MOF, NaCu3(mtz)4 (1, mtz = 5-methyltetrazolate), was prepared. It possesses a 3D framework with 1D channels and exhibits outstanding thermal and chemical stabilities under various conditions, including water, organic solvents, and acidic and basic solutions of wide pH range. The compound exhibits strong green emissions, which can be ascribed to metal-to-ligand charge transfer, and selective fluorescence sensing for pollutant nitrobenzene. Moreover, compound 1 presents a high proton conductivity of over 10–2 S cm–1 at 70 °C and 100% relative humidity. In 1, abundant uncoordinated nitrogen atoms on the pore walls act as H-bonding acceptors to achieve its high proton conductivity under water-assisted conditions. The compound is an unprecedented water-dependent proton conductor of the tetrazole-based MOF, providing a new avenue to design robust and high-performance proton-conductive MOFs.

Cryptic solvation dynamics of potential antineoplastic Azapodophyllotoxin: Short and long range charge transfer and distinct H-bonding motifs demystify its swinging emissive behaviour

Azapodophyllotoxin, the nitrogen analogue of antitumor podophyllotoxin, are new series of fascinating aspirants of anticancer drugs. The potential bioactive azapodophyllotoxin 5-(2-Hydroxyethyl)-9-(3,4,5-trimethoxyphenyl)-6,9-dihydro-[1,3]dioxolo[4,5–g]furo[3,4–b]quinolin-8(5H)-one (HTDQ) has been found to be highly effective against various cancer cell lines as compared to its minimal toxicity against normal cell lines. With an ulterior motive of exploring fluorescence properties of this promising antineoplastic candidate in biological environment, the intricate details of its ground and excited state solvation and solvation dynamics are investigated using steady state and Time resolved spectroscopic techniques. The experimental observations are substantiated by DFT and TD-DFT based quantum chemical calculations along with in silico molecular dynamics simulation. The solvatochromic behaviour of HTDQ reveals its sensitivity towards solvent polarity and proticity. The charge delocalization within HTDQ framework in ground state (G.S) entirely differs from that of in excited state (E.S). The change in polarity of the medium induces a peculiar short range intramolecular charge delocalization in G.S itself, forming a zwitterionic structure and endorses the unusual absorption characteristics. Whereas, in the E.S, it undergoes a long range intramolecular charge transfer (ICT). In non-polar solvents, the long range ICT induces stacking interaction between two dipolar HTDQ molecules leading to the formation of a new short-lived less emissive excimer species. However, in aprotic and protic polar solvents, the scenario is individually different due to the presence of H-bond donor (hydroxyl hydrogen atom) as well as acceptor sites (oxygen atoms) in the molecular framework of HTDQ. In aprotic solvents, the formation of H-bonds occurs due to presence of hydrogen acceptor site in the solvent that boost up the emission intensity to its maxima. In polar protic solvents, HDTQ subsumes both of its H-bond donor and acceptor sites and further strengthens the H-bonding interactions, which essentially stabilizes the probe molecule within the solvent shell and open up the non-radiative decay channels thereby reducing the emission intensity. HTDQ exhibits bathochromic shift in the emission spectra with increasing solvent polarity, with some exceptional shifts in 1,4 dioxane and THF, which may stem from another interesting conformational polarization of non-polar chair form to polar boat form of the solvent itself. Thus, the different spectroscopic aspects dealt herein demystify the impact of solvent milieu on the solute–solvent interactions and the interesting emissive nature of this potential therapeutic HTDQ that may provide impetus to develop new class of theragnostic agent with promising imaging capability and improved anti-neoplastic activities.

Three-dimension hierarchical composite via in-situ growth of Zn/Al layered double hydroxide plates onto polyaniline-wrapped carbon sphere for efficient naproxen removal

In this work, a novel adsorbent, 3D hierarchical CS@PANI@ZnAl-LDH composite, has been successfully fabricated through the hydrothermal synthesis of the carbon sphere, oxidative polymerization of polyaniline, and in-site growth of ZnAl-layered double hydroxides, simultaneously applied for the naproxen removal from aqueous solutions. The dynamics and isotherms fit better with the pseudo-second-order and Langmuir model, demonstrating the chemisorption, monolayer, and endothermic process. In addition, the high uptake capacities of CS@PANI@ZnAl-LDH for naproxen was 545.5 mg/g at 298 K when the pH was 5.0, outperforming most previously reported materials. Moreover, after five adsorption-desorption cycles, the spent CS@PANI@ZnAl-LDH maintains high removal efficiency and structural composition, revealing excellent recyclability and stability. Furthermore, Fourier transformed infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) analyses indicate electrostatic interactions, π-π interactions, and hydrogen bonding between CS@APNI@ZnAl-LDH and naproxen. Quantitative analyses, Localized orbit locator (LOL)-π isosurface, and Independent Gradient Model further verify the adsorption mechanisms mentioned above, indicating the synergistic effects between PANI and ZnAl-LDH improve the elimination ability for naproxen. Significantly, Hirshfeld surface analyses reveal that naproxen behaves as the H-bond acceptor, and the ZnAl-LDH acts as the H-bond donor. This work provided a feasible way to design purification materials for wastewater treatment.

Explicit solvent effects on (1 1 0) ruthenium oxide surface wettability: Structural, electronic and mechanical properties of rutile RuO2 by means of spin-polarized DFT-MD

The structural, electronic and mechanical properties of crystalline ruthenium dioxide RuO2 in its rutile structure have been calculated via forefront spin-polarized Density Functional Theory (DFT) and DFT-Molecular Dynamics (DFT-MD) simulations. Notwithstanding RuO2 is known as a highly active catalyst for a wide number of (photo) electrochemical reactions in aqueous/humid environments, the study of the interaction of RuO2 surfaces with water has been confined largely to (static) surface science and water adsorption calculations. Herein, an atomistic understanding of bulk rutile RuO2 and explicit solvent effects on (110)-RuO2 facet are provided. We especially focus on the comprehension of the mechanistic interplay between surface wettability, interfacial water dynamics and surface chemical activity.Analysis and characterization of the interfacial water and H-bond environment reveal how explicit liquid water and its dynamics play a role in the surface reconstruction and in the hydrophobic nature of the (110)-RuO2 facet with a prevailing H-bond acceptor character. Moreover, we provide a dependence of physical and chemical properties, such as surface electric field and work function, from different degrees of surface wettability of the (110)-RuO2 facet. Results on bulk properties of crystalline ruthenium dioxide RuO2 are in good agreement with the nowadays available experimental evidences and previous DFT studies.

Guest-Mediated Hierarchical Self-Assembly of Dissymmetric Organic Cages to Form Supramolecular Ferroelectrics

Guest-Mediated Hierarchical Self-Assembly of Dissymmetric Organic Cages to Form Supramolecular Ferroelectrics

Customized H-bonding acceptor and aperture chemistry within a metal-organic framework for efficient C3H6/C3H8 separation

Efficient separation of propylene/propane (C3H6/C3H8) is an imperative and extremely challenging process in the petrochemical industry due to their similar physicochemical characters. Known tactics mainly concentrate on unilateral thermodynamic or kinetic driven. Here, we report the efficient separation of C3H6/C3H8 through cooperative equilibrium-kinetic synergetic effect in a nodes-engineered Zr-MOF scaffold (1to). The grafted -CF3 motif with different isomers and resultant aperture chemistry awards 1to a late-model paradigm for efficient separation of C3H6/C3H8. Detailly, confined -CF3 group having the role of H-bonding acceptor can result in improved adsorption enthalpy (Qst) of 38.1 kJ mol−1, ideal adsorbed solution theory (IAST) selectivity of 80 and experimental selectivity of 25, respectively, indicating a marked thermodynamic driven for trapping C3H6. Besides, the contracted cross-sectional size and eligible pore shape of 1to could be judiciously adjusted through rationally engineering the pore microenvironment, yielding a topmost simulated diffusion selectivity of 408, which was 40.8 times higher than that of the pristine 1 example (10), effectively enabling the swift diffusion behavior of C3H6. Modeling simulations and breakthrough experiments confirmed the excellent C3H6/C3H8 separation performance of 1to. This work successfully developed a novel nodes-engineered strategy for C3H6 capture through equilibrium-kinetic synergetic effect, anticipating to set a new benchmark for gas separation and affording constructive guidance for tailoring delicate aperture chemistry.

Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE.

AMPylation is a prevalent posttranslational modification that involves the addition of adenosine monophosphate (AMP) to proteins. Exactly how Huntingtin-associated yeast-interacting protein E (HYPE), as the first human protein, is involved in the transformation of the AMP moiety to its substrate target protein (the endoplasmic reticulum chaperone binding to immunoglobulin protein (BiP)) is still an open question. Additionally, a conserved glutamine plays a vital key role in the AMPylation reaction in most filamentation processes induced by the cAMP (Fic) protein. In the present work, the detailed catalytic AMPylation mechanisms in HYPE were determined based on the density functional theory (DFT) method. Molecular dynamics (MD) simulations were further used to investigate the exact role of the inhibitory glutamate. The metal center, Mg2+, in HYPE has been examined in various coordination configurations, including 4-coordrinated, 5-coordinated and 6-coordinated. DFT calculations revealed that the transformation of the AMP moiety of HYPE with BiP followed a sequential pathway. The model with a 4-coordinated metal center had a barrier of 14.7 kcal/mol, which was consistent with the experimental value and lower than the 38.7 kcal/mol barrier of the model with a 6-coordinated metal center and the 31.1 kcal/mol barrier of the model with a 5-coordinated metal center. Furthermore, DFT results indicated that Thr518 residue oxygen directly attacks the phosphorus, while the His363 residue acts as H-bond acceptor. At the same time, an MD study indicated that Glu234 played an inhibitory role in the α-inhibition helix by regulating the hydrogen bond interaction between Arg374 and the Pγ of the ATP molecule. The revealed sequential pathway and the inhibitory role of Glu234 in HYPE were inspirational for understanding the catalytic and inhibitory mechanisms of Fic-mediated AMP transfer, paving the way for further studies on the physiological role of Fic enzymes.

Electric Field and Temperature Effects on the Ab Initio Spectroscopy of Liquid Methanol

Although many H-bonded systems have been extensively investigated by means of infrared (IR) spectroscopy, the vibrational response to externally applied electric fields of polar liquids remains poorly investigated. However, local electric fields along with quantum-mechanical interactions rule the behavior of H-bonded samples at the molecular level. Among the many H-bonded systems, liquid methanol holds a key place in that it exhibits a very simple H-bond network where, on average, each molecule acts as a single H-bond donor and, at the same time, as a single H-bond acceptor. Here we report on the IR spectra emerging from a series of state-of-the-art ab initio molecular dynamics simulations of bulk liquid methanol under the action of static and homogeneous electric fields. In addition, the same analysis is here conducted in the absence of the external field and for different temperatures. Although some electric-field-induced effects resemble the response of other polar liquids (such as the global contraction of the IR spectrum upon field exposure), it turns out that, distinctly from water, the “electrofreezing” phenomenon is unlikely to happen in liquid methanol. Finally, we provide atomistic analyses magnifying the completely different nature of electric-field- and temperature-induced effects on bulk liquid methanol and on its vibrational response.