Crystallographic Aspects, Photophysical Properties, and Theoretical Survey of Tetrachlorometallates of Group 12 Metals [Zn(II), Cd(II), and Hg(II)] with a Triply Protonated 2,4,6-Tris(2-pyridyl)-1,3,5-triazine Ligand.

Zn(II) (complex 1), Cd(II) (complex 2), and Hg(II) (complex 3) complexes have been synthesized using a triply protonated tptz (H3tptz3+) ligand and characterized mainly by single-crystal X-ray analysis. The general formula of all of the complexes is (H3tptz)3+·Cl-·[MCl4]2-·nH2O (where n = 1, 1.5, and 1.5 for complexes 1, 2, and 3, respectively). The crystallographic analysis reveals that the anion···π, anion···π+, and several hydrogen bonding interactions play a fundamental role in the stabilization of the self-assembled architectures that in turn help to enhance the dimensionality of all of the complexes. In addition, Hirshfeld surfaces and fingerprint plots have been deployed here to visualize the similarities and differences in hydrogen bonding interactions in 1-3, which are very important in forming supramolecular architectures. A density functional theory (DFT) study has been used to analyze and rationalize the supramolecular interactions by using molecular electrostatic potential (MEP) surfaces and combined QTAIM/NCI plots. Then, the device parameters for the complexes (1-3) have been thoroughly investigated by fabricating a Schottky barrier diode (SBD) on an indium tin oxide (ITO) substrate. It has been observed that the device made from complex 2 is superior to those from complexes 1 and 3, which has been explained in terms of band gaps, differences in the electronegativities of the central metal atoms, and the better supramolecular interactions involved. Finally, theoretical calculations have also been performed to analyze the experimental differences in band gaps as well as electrical conductivities observed for all of the complexes. Henceforth, the present work combined supramolecular, photophysical, and theoretical studies regarding group 12 metals in a single frame.

Conceptual DFT-Based Computational Peptidology, Pharmacokinetics Study and ADMET Report of the Veraguamides A-G Family of Marine Natural Drugs.

As a continuation of our research on the chemical reactivity, pharmacokinetics and ADMET properties of cyclopeptides of marine origin with potential therapeutic abilities, in this work our already presented integrated molecular modeling protocol has been used for the study of the chemical reactivity and bioactivity properties of the Veraguamides A-G family of marine natural drugs. This protocol results from the estimation of the conceptual density functional theory (CDFT) chemical reactivity descriptors together with several chemoinformatics tools commonly considered within the process of development of new therapeutic drugs. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides, and it is a protocol that allows the estimation with great accuracy of the CDFT-based reactivity descriptors and the associated physical and chemical properties, which can aid in determining the ability of the studied peptides to behave as potential useful drugs. Moreover, the superiority of the MN12SX density functional over other long-range corrected density functionals for the prediction of chemical and physical properties in the presence of water as the solvent is clearly demonstrated. The research was supplemented with an investigation of the bioactivity of the molecular systems and their ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as is customary in medicinal chemistry. Some instances of the CDFT-based chemical reactivity descriptors' capacity to predict the pKas of peptides as well as their potential as AGE inhibitors are also shown.

Formation Mechanism of Inter-Crosslink in DNA by Nitrogen Oxides Pollutants through A Diazonium Intermediate.

Outdoor air pollution is a mixture of multiple atmospheric pollutants, among which nitrogen oxide (NOx) stands out due to its association with several diseases. NOx reactivity can conduct to DNA damage as severe as interstrand crosslinks (ICL) formation, that in turn is able to block DNA replication and transcription. Experimental studies have suggested that the ICL formation due to NOx is realized through a diazonium intermediate (DI). In this work, we have modeled the DI structure, including a DNA double-strand composed of two base pairs GC/CG, being diazotized as one of the guanine nucleotides. The structural stability of DNA with DI lesion was essayed through 500 ns molecular dynamics simulations. It was found that the DNA structure of the oligonucleotide is stable when the DI is present since the loss of a Guanine-Cytosine hydrogen bond is replaced by the presence of two cation-π interactions. Additionally, we have studied the mechanism of formation of a crosslink between the two guanine nucleobases from the modeled DI by carrying out DFT calculations at the M06-L/DNP+ level of theory. Our results show that the mechanism is thermodynamically favored by a strong stabilization of the ICL product, and the process is kinetically viable since its limiting stage is accessible.

N-((1H-Pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine and Its Co(II) and Cu(II) Complexes as Antimicrobial Agents: Chemical Preparation, In Vitro Antimicrobial Evaluation, In Silico Analysis and Computational and Theoretical Chemistry Investigations.

Researchers are interested in Schiff bases and their metal complexes because they offer a wide range of applications. The chemistry of Schiff bases of heterocompounds has got a lot of attention because of the metal's ability to coordinate with Schiff base ligands. In the current study, a new bidentate Schiff base ligand, N-((1H-pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine (MPM) has been synthesized by condensing 6-methoxypyridine-3-amine with pyrrole-2-carbaldehyde. Further, MPM is used to prepare Cu(II) and Co(II) metal complexes. Analytical and spectroscopic techniques are used for the structural elucidation of the synthesized compounds. Both MPM and its metal complexes were screened against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae species for antimicrobial studies. Furthermore, these compounds were subjected to in silico studies against bacterial proteins to comprehend their best non-bonded interactions. The results confirmed that the Schiff base ligand show considerably higher binding affinity with good hydrogen bonding and hydrophobic interactions against various tested microbial species. These results were complemented with a report of the Conceptual DFT global reactivity descriptors of the studied compounds together with their biological scores and their ADMET computed parameters.

Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy.

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of -8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

Investigation of Antifungal Properties of Synthetic Dimethyl-4-Bromo-1-(Substituted Benzoyl) Pyrrolo[1,2-a] Quinoline-2,3-Dicarboxylates Analogues: Molecular Docking Studies and Conceptual DFT-Based Chemical Reactivity Descriptors and Pharmacokinetics Evaluation.

Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein ß-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation.

Unraveling the NaCl Concentration Effect on the First Stages of α-Synuclein Aggregation.

Intraneuronal aggregation of the intrinsically disordered protein α-synuclein is at the core of Parkinson's disease and related neurodegenerative disorders. Several reports show that the concentration of salts in the medium heavily affects its aggregation rate and fibril morphology, but a characterization of the individual monomeric conformations underlying these effects is still lacking. In this work, we have applied our α-synuclein-optimized coarse-grained molecular dynamics approach to decipher the structural features of the protein monomer under a range of NaCl concentrations (0.0-1.0 M). The results show that key intramolecular contacts between the terminal domains are lost at intermediate concentrations (leading to extended conformations likely to fibrillate), but recovered at high concentrations (leading to compact conformations likely to evolve toward amorphous aggregates). The pattern of direct interactions of the terminal α-synuclein domains with Na+ and Cl- ions plays a key role in explaining this effect. Our results are consistent with a recent study reporting a fibrillation enhancement at moderate NaCl concentrations but an inhibition at higher concentrations. The present work will contribute to improving our understanding of the structural features of monomeric α-synuclein, determining its NaCl-induced fibrillation propensity and the molecular basis of synucleinopathies, necessary for the future development of disease-halting therapies.

Synthesis, X-ray Characterization and Density Functional Theory (DFT) Studies of Two Polymorphs of the α,α,α,α, Isomer of Tetra-p-Iodophenyl Tetramethyl Calix[4]pyrrole: On the Importance of Halogen Bonds.

This manuscript reports the improved synthesis of the α,α,α,α isomer of tetra-p-iodophenyl tetra-methyl calix[4]pyrrole and the X-ray characterization of two solvate polymorphs. In the solid state, the calix[4]pyrrole receptor adopts the cone conformation, including one acetonitrile molecule in its aromatic cavity by establishing four convergent hydrogen bonds between its nitrogen atom and the four pyrrole NHs of the former. The inclusion complexes pack into rods, displaying a unidirectional orientation. In turn, the rods form flat 2D-layers by alternating the orientation of their p-iodo substituents. The 2D layers stack on top of another, resulting in a head-to-head and tail-to-tail orientation of the complexes or their exclusive arrangement in a head-to-tail geometry. The dissimilar stacking of the layers yields two solvate polymorphs that are simultaneously present in the structures of the single crystals. The ratio of the two polymorph phases is regulated by the amount of acetonitrile added to the chloroform solutions from which the crystals grow. Halogen bonding interactions are highly relevant in the crystal lattices of the two polymorphs. We analyzed and characterized these interactions by means of density functional theory (DFT) calculations and several computational tools. Remarkably, single crystals of a solvate containing two acetonitrile molecules per calix[4]pyrrole were obtained from pure acetonitrile solution.

Preparation, Spectroscopic Characterization, Theoretical Investigations, and In Vitro Anticancer Activity of Cd(II), Ni(II), Zn(II), and Cu(II) Complexes of 4(3H)-Quinazolinone-Derived Schiff Base.

Herein, we report the synthesis and characterization of a new Schiff base ligand 3-[[(E)-(3-hydroxyphenyl)-methylidene]amino]-2-methyl-quinazolin-4(3H)-one (HAMQ) and its Cd(II), Ni(II), Zn(II), and Cu(II) complexes (C1-C4). The ligand HAMQ was synthesized by reacting 3-hydroxybenzaldehyde and 3-amino-2-methyl-4(3H)-quinazolinone in a 1:1 molar ratio. The structure of the ligand and its complexes (C1-C4) were evaluated using ultraviolet (UV)-visible (Vis) light spectroscopy, 1H-NMR, Fourier-transform infrared (FT-IR) spectroscopy, MS, elemental analysis, conductance data, and thermogravimetric analysis (TGA). The characterization results suggested that the bidentate ligand, HAMQ, coordinated to the metal center through the lactum oxygen and the azomethine nitrogen. Moreover, all the metal complexes were analyzed using powder X-ray diffraction studies, which revealed that all of them belong to a triclinic crystal system. The research was supplemented by density functional theory (DFT) studies on the IR and UV-Vis spectra, as well as the chemical reactivity of the HAMQ and its four metallic derivatives making use of conceptual density functional theory (CDFT) by means of KID (Koopmans in DFT) methodology. The synthesized complexes displayed significant in vitro anticancer activity against human cancer cell lines (HeLa and HCT-115).

A Coarse-Grained Molecular Dynamics Approach to the Study of the Intrinsically Disordered Protein α-Synuclein.

Intrinsically disordered proteins (IDPs) are not well described by a single 3D conformation but by an ensemble of them, which makes their structural characterization especially challenging, both experimentally and computationally. Most all-atom force fields are designed for folded proteins and give too compact IDP conformations. α-Synuclein is a well-known IDP because of its relation to Parkinson's disease (PD). To understand its role in this disease at the molecular level, an efficient methodology is needed for the generation of conformational ensembles that are consistent with its known properties (in particular, with its dimensions) and that is readily extensible to post-translationally modified forms of the protein, commonly found in PD patients. Herein, we have contributed to this goal by performing explicit-solvent, microsecond-long Replica Exchange with Solute Scaling (REST2) simulations of α-synuclein with the coarse-grained force field SIRAH, finding that a 30% increase in the default strength of protein-water interactions yields a much better reproduction of its radius of gyration. Other known properties of α-synuclein, such as chemical shifts, secondary structure content, and long-range contacts, are also reproduced. Furthermore, we have simulated a glycated form of α-synuclein to suggest the extensibility of the method to its post-translationally modified forms. The computationally efficient REST2 methodology in combination with coarse-grained representations will facilitate the simulations of this relevant IDP and its modified forms, enabling a better understanding of their roles in disease and potentially leading to efficient therapies.

A Systematic DFT Study of Some Plausible Zn(II) and Al(III) Interaction Sites in N-Terminally Acetylated α-Synuclein.

The interactions between the protein α-synuclein and the Zn(II) and Al(III) cations at different sites were studied at the M06/6-311+G(d,p)/SMD and the ωB97X-D/6-311+G(d,p)/SMD levels of theory. For Zn(II), previous experimental studies determined the presence of a high affinity site at Asp121 and a lower affinity one at His50. As for Al(III), an in vitro study showed it to be the most effective cation to induce structural changes in α-synuclein and to accelerate its aggregation. Besides Zn(II) and Al(III), Cu(II) also binds α-synuclein (in fact, its complexes are the most studied and the best characterized ones) forming square planar complexes, and several binding sites are known for it, involving Met1-Asp2 (only in nonacetylated α-synuclein), His50, and Asp121. Herein, we applied a simple theoretical methodology, which satisfactorily reproduces experimental geometries and energies for complexes of N-terminally acetylated α-synuclein with Cu(II), to study Zn(II) and Al(III) complexes at those same sites, as well as at some structurally analogous alternative sites. We found binding geometries for Zn(II) and Al(III) that differ from the ones for Cu(II). These results can help to understand the interactions between α-synuclein and metals, one of the factors leading to the formation of potentially neurotoxic α-synuclein aggregates.

Copper(II) Binding Sites in N-Terminally Acetylated α-Synuclein: A Theoretical Rationalization.

The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121. However, in the N-terminally acetylated protein, present in vivo, the Met1 site is blocked. In this work, we simplify the representation of the protein by modeling each experimentally found binding site as a complex between an N-terminally acetylated α-synuclein dipeptide (or several independent residues) and a Cu(II) cation, and compare the results with a number of additional, structurally analogous sites not experimentally found. This way of representing the binding sites, although extremely simple, allows us to reproduce experimental results and to provide a theoretical rationale to explain the preference of Cu(II) for certain sites, as well as explicit geometrical structures for the complexes formed. These results are important to understand the interactions between α-synuclein and Cu(II), one of the factors inducing structural changes in the protein and leading to aggregated forms of it which may play a role in neurodegeneration.

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition.

Zoledronate and risedronate are the most powerful available nitrogen-containing bisphosphonates used in the treatment of bone-resorption disorders. Knowledge about inhibition mechanisms of these molecules is based on available crystallographic structures of human farnesyl pyrophosphate synthase (hFPPS). However, there is a lack of information explaining the inhibition potency of these two molecules compared to the natural substrate, dimethylallyl pyrophosphate. We carried out a molecular dynamics study that shown: (1) that NBPs potency is related to higher electrostatic interactions with the metallic cluster of the active site than to the natural substrate, and (2) the protonation of the R2 side chain is a critical factor to stabilize the NBPs into a closely irreversible ternary complex with the hFPPS.

Human farnesyl pyrophosphate synthase inhibition by nitrogen bisphosphonates: a 3D-QSAR study.

We report the results of a comparative molecular field analysis and comparative molecular similarity index analysis of the human farnesyl pyrophosphate synthase (FPPS) inhibition by nitrogen bisphosphonates (NBPs) taking into account their time-dependent inhibition efficacies. The 3D-QSAR models obtained provide steric, electrostatic and hydrophobic contour maps consistent with the interactions into the active site of human FPPS observed in available crystallographic structures. Furthermore, the 3D-QSAR models obtained provide accurately IC50 values of the NBPs of the training set. The predictive ability of these 3D-QSAR models was found to rely on the choice of biologically active conformations of the target molecules and on a careful examination of the protonation status of the NBPs in the training set. The best models obtained can be useful to predict biological values of a high number of NBPs that have been used for the treatment of different diseases as potential inhibitors of the activity of the FPPS enzyme.

Theoretical calculations of stability constants and pKa values of metal complexes in solution: application to pyridoxamine-copper(II) complexes and their biological implications in AGE inhibition.

Accurate prediction of thermodynamic constants of chemical reactions in solution is one of the current challenges in computational chemistry. We report a scheme for predicting stability constants (log ß) and pKa values of metal complexes in solution by means of calculating free energies of ligand- and proton-exchange reactions using Density Functional Theory calculations in combination with a continuum solvent model. The accuracy of the predicted log ß and pKa values (mean absolute deviations of 1.4 and 0.2 units respectively) is equivalent to the experimental uncertainties. This theoretical methodology provides direct knowledge of log ß and pKa values of major and minor species, so it is of potential use in combination with experimental techniques to obtain a detailed description of the microscopic equilibria. In particular, the proposed methodology is shown to be especially useful for obtaining the real acidity constants of those chelates where the metal-ligand coordination changes as a result of ligand deprotonation. The stability and acidity constants of pyridoxamine-Cu(2+) chelates calculated with the proposed methodology show that pyridoxamine is an efficient scavenging agent of Cu(2+) under physiological pH conditions. This is of special interest as Cu(2+) overload is involved in the formation of advanced glycation end-products (AGEs) and their associated degenerative medical conditions.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Molecular insights into the in silico discovery of corilagin from Terminalia chebula as a potential dual inhibitor of SARS-CoV-2 structural proteins.

The spike (S) glycoprotein and nucleocapsid (N) proteins are the crucial pathogenic proteins of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus during its interaction with the host. Even FDA-approved drugs like dexamethasone and grazoprevir are not able to curb the viral progression inside the host and are reported with adverse effects on body metabolism. In this context, we aim to report corilagin a novel, potential dual inhibitor of S and N proteins from Terminalia chebula. The bioactive compounds of T. chebula were subjected to a series of computational investigations including molecular docking simulations, molecular dynamics (MD) simulations, binding free energy calculations, and PASS pharmacological analysis. The results obtained from these studies revealed that corilagin was highly interactive with the S (-8.9 kcal/mol) and N (-9.2 kcal/mol) proteins, thereby showing dual inhibition activity. It was also found to be stable enough to induce biological activity inside the inhibitor binding pocket of the target enzymes throughout the dynamics simulation run for 100 ns. This is also confirmed by the changes in the protein conformations, evaluated using free energy landscapes. Outcomes from this investigation identify corilagin as the lead potential dual inhibitor of S and N proteins of SARS-CoV-2, which could be taken for biological studies in near future.Communicated by Ramaswamy H. Sarma.

Formation of Schiff bases of O-phosphorylethanolamine and O-phospho-D,L-serine with pyridoxal 5'-phosphate. experimental and theoretical studies.

Pyridoxal 5'-phosphate (PLP) is a B(6) vitamer acting as an enzyme cofactor in various reactions of aminoacid metabolism and inhibiting glycation of biomolecules. Nonenzymatic glycation of aminophospholipids alters the stability of lipid bilayers and cell function as a result. Similarly to protein glycation, aminophospholipid glycation initially involves the formation of a Schiff base. In this work, we studied the formation of Schiff bases between PLP and two compounds mimicking the polar head of natural aminophospholipids, namely: O-phosphorylethanolamine and O-phospho-D,L-serine. Based on the results, the pH-dependence of the microscopic constants of the two PLP-aminophosphate systems studied is identical with that for PLP-aminoacid systems. However, the rate and equilibrium formation constants for the Schiff bases of the aminophosphates are low relative to those for the aminoacids. A theoretical study by density functional theory of the formation mechanism for the Schiff bases of PLP with the two aminophospholipid analogues confirmed that the activation energy of formation of the Schiff bases is greater with aminophosphates; on the other hand, that of hydrolysis is essentially similar with aminoacids and aminophosphates.

Insight into charge transportation in cadmium based semiconducting organic-inorganic hybrid materials and their application in the fabrication of photosensitive Schottky devices.

A coordination polymer (1) and a trinuclear complex (2) have been synthesized using a compartmental N2O2O2' donor Schiff base ligand. Both complexes are characterized using different spectroscopic techniques and their structures are determined using single crystal X-ray diffraction analyses. Energies associated with different non-covalent (S⋯O chalcogen bonds, C-H⋯H-C, C-H⋯I and C-H⋯π) interactions in the solid state of both complexes have been calculated using the Turbomole program. Investigations of electrical conductivity and photosensitivity of both complexes reveal that suitable Schottky diode devices could be fabricated from both complexes. The current vs. voltage plots of the complex based devices have been used to calculate the conductivity under dark and irradiation conditions. In both complexes the charge transportation mainly occurs through space which involves the hopping process. Standard band theory has been used to compare the experimental and theoretical results of optoelectronic measurements. The calculations confirm that both are direct band gap (2.78 and 3.30 eV) semiconductors and that complex 1 exhibits a lower band gap, in line with the experimental results (3.21 and 3.43 eV in 1 and 2, respectively).