Copper(II) Schiff base complex derived from salen ligand: structural investigation, Hirshfeld surface analysis, anticancer and anti-SARS-CoV-2.

This work deals with the synthesis and characterization of copper(II) complex [Cu(salen)(H2O)](1) of salen-type Schiff base ligand derived from the condensation of 5-bromo-2-hydroxy-3-methoxybenzaldehyde and ethylenediamine in EtOH. This complex was characterized by different spectroscopic and physicochemical methods. Single crystal X-ray crystallography study revealed that Cu(II) in complex (1) is five-coordinate and adopts a distorted square pyramidal geometry. A DFT calculation was employed to evaluate the optimized electronic structure, HOMO-LUMO, energy gap, and global parameters. A detailed structural and non-covalent interaction on the complex is investigated by single crystal structure analysis and computational approaches. The strength of the interaction and 3D topology of the crystal packing are visualized through an energy framework. Hirshfeld surface and 2D fingerprint plots have been explored in the crystal structure of the complex. The anticancer properties of copper(II) complex was studied against the selected cancerous cell lines of breast cancer, cervical cancer, colon cancer and hepatocellular carcinoma. Additionally, molecular docking and MD simulations was performed on the complex to predict the binding mode and interactions between the ligand and the main protease of the SARS-CoV-2 (PDB ID: 7CBT and 7D1M). The molecular docking calculations of the complex (1) with SARS-CoV-2 virus revealed the binding energy of -8.1 kcal/mol and -7.5 kcal/mol with an inhibition constant of 3.245 µM and 2.318 µM at inhibition binding site of receptor towards 7CBT and 7D1M main protease (Mpro), respectively. Besides this, molecular docking results (-7.6 kcal/mol, 3.196 µM) towards Escherichia coli PBP2 targets (PDB ID: 6G9S) was also studied. Communicated by Ramaswamy H. Sarma.

Synthesis, theoretical calculations, X-ray, HS and energy framework analysis, molecular docking of amino pyrazole containing azo dye and its inhibition activity of COVID-19 main protease

The synthesis and characterization of 5-Amino-4-Phenylazo-3-Methyl-1-(2-hydroxyethyl) Pyrazole (AD2a) were investigated in our study. The novel synthesized pyrazole-based disperse diazo dye has been elucidated by using UV–Vis, FT-IR, elemental analysis, LC/MS-MS, NMR and X-ray analysis. The AD2a molecule containing pyrazole and phenyl rings, hydroxy‑ethyl and azo group moieties crystallized in the orthorhombic space group Pbca. The crystal structures of AD2a are consolidated by N(3)-H(3A)⋯O(1) and O(1)-H(1)⋯N(5) intermolecular hydrogen bonds. The geometry of AD2a has been optimized with the DFT calculation B3LYP/6–31G(d,p) level and it has been observed that the obtained results give very good results with the X-ray diffraction data. The theoretical vibrational analysis, frontier orbital energies, electronic absorption spectrum, electronic properties, global reactivity descriptors and other theoretical parameters were obtained by using the same DFT method. Additionally, Hirshfeld surface analysis (HSA) with 2D fingerprint plots (FP) was performed to estimate contacts and the energy framework diagrams of AD2a (Eele, Edis and Etot) were determined. The inhibitor-receptor relationship established by the molecular docking study confirmed the inhibition activity of the AD2a construct against COVID-19. It showed that the AD2a molecule, shown as a drug candidate, binds strongly to SARS-CoV-2 (Mpro) (-6.5 kcal/mol) receptors.

Structural and Computational Studies of Cobalt(II) and Copper(II) Complexes with Aromatic Heterocyclic Ligand

Two coordination complexes, a cobalt(II) complex tris(1,10-phenanthroline)-cobalt perchlorate hydrate, [Co(phen)3]·(ClO4)2·H2O(1), and a copper(II) complex tris(1,10-phenanthroline)-copper perchlorate 4-bromo-2-{[(naphthalene-1-yl)imino]methyl}phenol hydrate, [Cu(phen)3]·(ClO4)2·HL·[O] (2), [where, phen = 1,10-phenathroline as aromatic heterocyclic ligand, HL = 4-bromo-2-((Z)-(naphthalene-4-ylimino) methyl) phenol] have been synthesized and structurally characterized. Single crystal X-ray analysis of both complexes has revealed the presence of a distorted octahedral geometry around cobalt(II) and copper(II) ions. density functional theory (DFT)-based quantum chemical calculations were performed on the cationic complex [Co(phen)3]2+ and copper(II) complex [Cu(phen)3]2+ to get the structure property relationship. Hirshfeld surface and 2-D fingerprint plots have been explored in the crystal structure of both the metal complexes. To find potential SARS-CoV-2 drug candidates, both the complexes were subjected to molecular docking calculations with SARS-CoV-2 virus (PDB ID: 7BQY and 7C2Q). We have found stable docked structures where docked metal chelates could readily bound to the SARS-CoV-2 Mpro. The molecular docking calculations of the complex (1) into the 7C2Q-main protease of SARS-CoV-2 virus revealed the binding energy of −9.4 kcal/mol with a good inhibition constant of 1.834 µM, while complex (2) exhibited the binding energy of −9.0 kcal/mol, and the inhibition constant of 1.365 µM at the inhibition binding site of receptor protein. Overall, our in silico studies explored the potential role of cobalt(II) complex (1), and copper(II) complex (2) complex as the viable and alternative therapeutic solution for SARS-CoV-2.

Synthesis, spectroscopic, crystallographic, quantum and molecular docking investigations of cis-4,5-diphenylimidazolidine-2-thione

We present the synthesis and characterization of stereoselective thione. The synthetic procedure includes readily available starting materials and minimum side products. The reaction of meso‑stilbenediamine with carbon disulphide in the presence of strong base gave cis-4,5-diphenylimidazolidine-2-thione (DPIT) in an excellent yield. The thione compound was characterized via FT-IR and mass spectroscopy. In addition, the crystal structure of it was determined by single crystal X-rays diffraction analysis which inferred that the molecular configuration was stabilized by intramolecular π⋯π stacking interaction. The crystal packing was mainly stabilized by N-H⋯S bonding. Hirshfeld surface analysis was performed for the exploration of the intermolecular interactions. Void analysis was carried out to predict the mechanical stability. Interaction energy between the molecular pairs is calculated which showed that the dispersion energy played a dominant role in the stabilization of the crystal packing. Moreover, the quantum computational methods were used to study the molecular structure and electronic properties of entitled compound. The molecular geometries were optimized for possible thione and thiole tautomeric structures. A comparison of total energy of molecular tautomers indicates that thione tautomer possesses lower total energy which is about 20.18 Kcal/mol lower than thiole tautomer. The electronic properties of thione derivative were studied including 3-D wavefunction delocalization of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals and their orbital energy gap. The HOMO-LUMO energy gap for DPIT was found to be 4.874 eV. The delocalization of wavefunction indicates the probable presence of HOMO and HOMO-1 are mainly localized over C-S bond owing to the presence of lone pair of electrons in the sulfur atom. Additionally, the molecular docking study was also carried out for main protease (Mpro) of SARS-CoV-2. The binding energy calculation and investigation of intermolecular interactions highlighted the probable inhibition tendency of DPIT for SARS-CoV-2. The present experimental and computational studies indicate a significant potential of entitled molecule for electronic and biological perspectives.

N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins

In this work, synthesis as well as detailed structural and computational analyses of the novel isoniazid derivative, namely N'-isonicotinoylpicolinohydrazonamide (1), are reported. The obtained compound was examined by microanalysis, IR, 1H NMR spectroscopy and single crystal X-ray diffraction. The crystal packing was studied by the Hirshfeld surface analysis. Molecules in the crystal structure of 1 are linked through N–H⋯O and N–H⋯N hydrogen bonds, and π⋯π interactions, yielding a 1D supramolecular chain. According to the Hirshfeld surface analysis, crystal packing of 1 is primarily dictated by H⋯H, H⋯C, H⋯N and H⋯O contacts, of which the latter three contacts are highly favoured. The crystal packing is further characterized by highly favoured C⋯C contacts. Compound 1 was also studied using DFT in gas phase, which revealed its pronounced electrophilic features. The most electron-rich (nucleophilic) sites were revealed for the carbonyl oxygen atom, and 4-pyridyl and imine nitrogen atoms, while the most electron-deficient (electrophilic) sites were found for the NH and NH2 hydrogen atoms. Compound 1 was predicted to belong to a fourth class of toxicity and exhibits negative blood–brain barrier penetration and positive gastrointestinal absorption property. In silico molecular docking was applied to probe 1 as a potential inhibitor of a series of the SARS-CoV-2 proteins and it was found that 1 is potentially active against all the applied proteins with the best activity against Nonstructural protein 3 (Nsp3_range 207–379-MES). It was also established that the best docking scores for 1 were found for the cavities, where initial ligands were located, except for the Papain-like protease (PLpro). The best binding affinity of the latter protein with 1 was revealed for the other cavity with about 0.8 kcal/mol being more efficient. Molecular dynamics simulations were also applied to evaluate the stability of complexes PLproI–1, PLproII–1 and Nsp_range 207–379-MES–1. Complex PLproI–1 was found to be highly unstable, while complexes PLproII–1 and Nsp_range 207–379-MES–1 are stable. © 2023 Elsevier Ltd

4-(4-methoxyphenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one: Synthesis, crystal structure, Hirshfeld surface analysis, noncovalent, ADMET studies and biological evaluation

Oxadiazines are heterocyclic compounds containing two nitrogen and one oxygen atom in a six-membered ring. The synthesis and crystal structure of 4-(4-methoxyphenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one (MPMP-OXA) was reported. The organic crystal structure of the synthesized compound was fully characterized by various spectroscopic techniques (Fourier Transform Infrared Spectroscopy, NMR and LC/MS-TOF) and single-crystal X-ray diffraction studies. The MPMP-OXA crystal structure crystallizes in the triclinic system and space group P-1 with a = 5.9395(15) Å, b = 11.471(3) Å, c = 11.901(3) Å, α = 70.075(4)°, β = 83.454(4)°, γ = 78.016(4)°, V = 744.9(3) Å3, Z = 2 cell parameters. This work is aimed to study the weak interactions in the crystal packing of a new synthesized oxadiazine derivate. The contributions of the most important intermolecular interactions in the crystal structure were investigated by 3D-Hirshfeld surface (HS) and 2D-fingerprint analysis. The C[sbnd]H···O interactions as the most important contributors to the crystal packing between the oxygen of the oxadiazine ring and the hydrogen atom of phenyl ring appear as bright red spots visible on the HS surface. The hydrogen-bonded interaction of MPMP-OXA has been investigated using noncovalent interactions approach. The molecular docking studies for the synthesized compound were performed to gain insight into the inhibition nature of this molecule against DNA Gyrase B Candida and 3-chymotrypsin-like protease (SARS-CoV main protease) proteins and resulted in good activities for new anti-agents. Lastly, Bioavailability, druggability as well as absorption, distribution, metabolism, excretion, and toxicity parameters (ADMET), and gastrointestinal absorption (BOILED-Egg method) properties of newly synthesized compound using smile codes were performed in detail. © 2023 Elsevier B.V.

Synthesis, analysis of mol-ecular and crystal structures, estimation of inter-molecular inter-actions and biological properties of 1-benzyl-6-fluoro-3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]-7-(piperidin-1-yl)quinolin-4-one.

The title compound, C30H33N4O2F, can be obtained via a two-step synthetic scheme involving 1-benzyl-6-fluoro-4-oxo-7-(piperidin-1-yl)-1,4-di-hydro-quino-line-3-carbo-nitrile as a starting compound that undergoes substitution with hydroxyl-amine and subsequent cyclization with 4-methyl-cyclo-hexane-1-carb-oxy-lic acid. It crystallizes from 2-propanol in the triclinic space group P with a mol-ecule of the title compound and one of 2-propanol in the asymmetric unit. After the mol-ecular structure was clarified using NMR and LC/MS, the mol-ecular and crystalline arrangements were defined with SC-XRD. A Hirshfeld surface analysis was performed for a better understanding of the inter-molecular inter-actions. One strong (O-H⋯O) and three weak [C-H⋯F (intra-molecular) and two C-H⋯O] hydrogen bonds were found. The contributions of short contacts to the Hirshfeld surface were estimated using two-dimensional fingerprint plots showing that O⋯H/H⋯O, C⋯H/H⋯C and C⋯C contacts are the most significant for the title compound and O⋯H for the 2-propanol. The crystal structure appears to have isotropically packed tetra-mers containing two mol-ecules of the title compound and two mol-ecules of 2-propanol as the building unit according to analysis of the distribution of pairwise inter-action energies. A mol-ecular docking study was carried out to evaluate the inter-actions of the title compound with the active centers of macromolecules corresponding to viral targets, namely, anti-hepatitis B activity [HBV, capsid Y132A mutant (VCID 8772) PDB ID: 5E0I] and anti-COVID-19 main protease activity (PDB ID: 6LU7). The data obtained revealed a noticeable affinity towards them that exceeded that of the reference ligands.

Structural and theoretical investigations, Hirshfeld surface analysis and anti-SARS CoV-2 of nickel (II) coordination complex.

A nickel(II) Schiff base complex, [Ni(L)(DMF)](1), was synthesized by treating NiCl2.6H2O with an ONS-donor Schiff base ligand(H2L) derived from the condensation 3,5-Dichlorosalicylaldehyde and 4,4-Dimethyl-3-thiosemicarbazide in DMF. The geometry around the center metal ion in [Ni(L)(DMF)](1) was square planar as revealed by the data collection from diffraction studies. DFT calculations were performed on the complex to get a structure-property relationship. Hirshfeld surface analysis was also carried out in the crystal structure of nickel (II) Schiff base complex. Additionally, inspiring from recent developments to find a potential inhibitor for SARS-CoV-2 virus, we have also performed molecular docking study of [Ni(L)(DMF)](1) to see if our novel complex show affinity for main protease (Mpro) of SARS-CoV-2 Mpro (PDB ID: 6LZE). Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant was found to be -6.6 kcal/mol and 2.358 µM, respectively, for the best docked confirmation of complex [Ni(L)(DMF)](1) with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of complex [Ni(L)(DMF)](1) is found to be better than that of recently docking results of anti-SARS-CoV-2 drugs like chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) when targeted to the active-site of SARS-CoV-2 Mpro. Besides this, molecular docking against G25K GTP-nucleotide binding protein (PDB ID: 1A4R) was also studied. We believe that current results can intrigue not only for the biomedical community but also for the materials chemists who are engaged to explore the application coordination complexes.Communicated by Ramaswamy H. Sarma.

Molecular docking with SARS-CoV-2 and potential drug property of a bioactive novel Zn(II) polymer: A combined experimental and theoretical study.

A new Zn(II) coordination polymer based on o-phthalato (Phth) and 2-aminopyridine (2-Ampy) viz. {[Zn(2-Ampy)2(Phth)]∙(H2O)]}n (1) has been synthesized at room temperature and characterized by elemental analyses, electronic spectroscopy, FT-IR spectroscopy, thermal analysis (TGA/DSC), powder X-ray diffraction (PXRD) and single crystal X-ray diffraction. The basic trimeric units of 1 form a polymeric chain by N-H⋯O and π⋯π interactions. These polymeric chains interconnect through various non-covalent interactions in two perpendicular directions to ultimately give rise to a 3D architecture of 1. The interesting non-covalent interactions in 1, contributing to its stability in the solid state are studied by Hirshfeld surface analysis and other different theoretical tools. Molecular docking study of 1 is performed against six different proteins of SARS-CoV-2. The drug potential of the synthesized compound is evaluated by ADMET calculations.

Experimental and theoretical studies of a thiourea derivative: 1-(4-Chloro-benzoyl)-3-(2-trifluoromethyl-phenyl)thiourea

The 1-(4-chloro-benzoyl)-3-(2-trifluoromethyl-phenyl)thiourea compound was synthesized by a two-step reaction and a single crystal of it was obtained by recrystallization method. Its structure was elucidated by elemental analyzes, FT-IR, 1H NMR, and 13C NMR techniques, and its molecular and crystal structure was also determined by single-crystal X-ray diffraction analysis. The Hirshfeld surface analyzes of the crystal structure indicate that the most important contributions for crystal packing are from H···H (23.8%), H···S/S···H (14.5%), H···F/F···H (14.3%), C···H/H···C (14.2%), and Cl···F/F···Cl (9.0%). In addition, energy-framework calculations are used to analyze and visualize the three-dimensional topology of the crystal packing. The electrostatic energy framework is dominant over the dispersion energy framework. The density functional theory method with the basis set of B3LYP/6-311G(d,p) has been employed to obtain the optimized structural geometry, Mulliken charges, molecular electrostatic potential, frontier molecular orbitals, the total density of states, reduced density gradient analysis and natural bond orbitals. The experimental crystal structure parameters and optimized structure parameters are very similar. The HOMO-LUMO energy gap of the compound is 3.5307 eV. Different global chemical reactivity descriptor parameters were also calculated. Nonlinear optical properties such as anisotropy of polarizability, mean polarizability, static dipole moment, and first-order hyperpolarizability values were theoretically determined. The Fukui functions as electron density-based local reactivity descriptors were also calculated to explain the chemical selectivity or the reactivity site in the molecule. Molecular docking studies were also carried out to determine the inhibitory action of the title compound against the main protease (6LU7) of a new coronavirus (COVID-19).

Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate.

Isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate (IDPC) was synthesized and characterized via spectroscopic (FT-IR and NMR) techniques. Hirshfeld surface and topological analyses were conducted to study structural and molecular properties. The energy gap (Eg), frontier orbital energies (EHOMO, ELUMO) and reactivity parameters (like chemical hardness and global hardness) were calculated using density functional theory with B3LYP/6-311++G (d,p) level of theory. Molecular docking of IDPC at the active sites of SARS-COVID receptors was investigated. IDPC molecule crystallized in the centrosymmetric triclinic ( P 1 ¯ ) space group. The topological and Hirshfeld surface analysis revealed that covalent, non-covalent and intermolecular H-bonding interactions, and electron delocalization exist in the molecular framework. Higher binding score (-6.966 kcal/mol) of IDPC at the active site of SARS-COVID main protease compared to other proteases suggests that IDPC has the potential of blocking polyprotein maturation. H-bonding and π-cationic and interactions of the phenyl ring and carbonyl oxygen of the ligand indicate the effective inhibiting potential of the compound against the virus.

One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach.

Although antimicrobial resistance before the Covid-19 pandemic is a top priority for global public health, research is already ongoing on novel organic compounds with antimicrobial and antiviral properties in changing medical environments in connection with Covid 19. Thanks to the Biginelli reaction, which allows the synthesis of pyrimidine compounds, blockers of calcium channels, antibodies, antiviral, antimicrobial, anti-inflammatory, or antioxidant therapeutic compounds were investigated. In this paper, we aim to present Biginelli's synthesis, its therapeutic properties, and the structural-functional relationship in the test compounds that allows the synthesis of antimicrobial compounds. Both the DFT and TD-DFT computations of spectral data, molecular orbitals (HOMO, LUMO) analysis, and electrostatic potential (MEP) surfaces are carried out as an add-on to synthetic research. Hirshfeld surface analysis was also used to segregate the different intermolecular hydrogen bonds involved in the molecular packing strength. Natural Bond Orbital (NBO) investigation endorses the existence of intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. The dipole moment, linear polarizability, and first hyperpolarizabilities have been explored as molecular parameters. All findings based on DFT exhibit the best consistency with experimental findings, implying that synthesized molecules are highly stable. To better understand the binding mechanism of the SARS-CoV-2 Mpro, we performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations.

Different phosphoric triamide [HN]3-nP(O)[N]n (n = 1, 2) skeletons lead to identical non-covalent interactions assemblies: X-ray crystallography investigation, Hirshfeld surface analysis and molecular docking study against SARS-CoV-2

In this work, we describe the crystal structures of two new phosphoramides containing the same [(3-Cl)C6H4NH]P(O) = Y segment (Y[N(CH3)CH2C6H5]2 (1) and Y[NC4H8O]2 (2)) and an improved model of [C6H11(CH3)N]P(O)[NHC(CH3)3]2 (compound 3). The structures are experimentally investigated by single crystal X-ray diffraction using two types of refinements with spherical (S) and aspherical (AS) [Hirshfeld atomic refinements (HARs)] form factors, FT-IR and 1H, 13C, 31P NMR spectroscopy. A biological molecular docking investigation gives hints to suggest an appropriate inhibitory activity against MPro of SARS-COV-2 (6M03 and 6LU7) especially for 1 with a binding energy around −6 (6M03)/−7 (6LU7) kcal/mol. In the present work, the docking simulations are carried out for the first time for three series of ligand (L)-protein (P) complexes: L (with S form)-P (6M03), L (with AS form)-P (6M03) and L (AS)-P (6M03-N, with hydrogen atoms at their theoretical neutron values), where the binding energies are approximately proved to be 0.8 kcal/mol lower for simulations with 6M03-N than those for 6M03. Moreover, the structural study illustrates that the hydrogen bond patterns of all three structures consist of one-dimensional zigzag chains formed by classical NH…O hydrogen bond interactions. Further stabilization is provided by weak interactions such as CH…Cl (for 1 and 2), Cl…π (for 1 and 2) and CH…O (for 2 and 3). Furthermore, the intermolecular interactions are analyzed by three-dimensional (3D) Hirshfeld surfaces, 2D fingerprint plots and enrichment ratios. The favored contacts identified by Hirshfeld surface analysis are H…O/O…H interactions covering the NH…O hydrogen bonds for all three structures. For 1 and 2, Cl…C/C…Cl contacts covering Cl…π interactions are recognized as the most enriched contacts.

Structural, spectral, bioactivity, antioxidant and molecular docking (with SARS-CoV-2) analyses on a new synthesized thiosemicarbazide derivative

Spectroscopic characterization of the N'-(4-nitrophenylcarbonothioyl) nicotinohydrazide molecule has been studied using both experimental (X-ray diffraction and IR spectroscopy) and quantum mechanical methods. The tautomeric energetic analysis, structural optimization parameters (bond lengths and angles), vibrational wave numbers, UV-Vis. parameters, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) analyses and Molecular Electrostatic Potential (MEP) surface have been calculated by using DFT/B3LYP method with 6-311++G(2d,2p) level of theory to compare with the experimental results. The radical scavenging activity of the synthesized new compound has been evaluated using three different test methods. For this purpose, 2,2'-azino-bis-(3- ethylbenzothiazoline-6-sulfonate) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests has been done. The pharmacokinetic, physicochemical, and toxicity properties have been defined by using drug-likeness and in silico ADMET studies. The interaction characterization with SARS-CoV-2 main protease (Mpro) of the title compound has been investigated via the help of a molecular docking study.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and molecular dynamic simulation studies of (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine derivatives.

A novel drug to treat SARS-CoV-2 infections and hydroxyl chloroquine analogue, (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine (BCMTP) compound has been synthesized in one pot reaction. The novel compound BCMTP has been characterized by FT-IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction patterns. Crystal packing is stabilized by C8-H8A•••Cl10i, C41-H41•••Cl1ii and N1-H1A•••Cl6iii intermolecular hydrogen bonds. From the geometrical parameters, it is observed that the piperidine ring adopts chair conformation. Hirshfeld surface analysis was carried out to quantify the interactions and an interaction energy analysis was done to study the interactions between pairs of molecules. The geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6-31G (d, p) as the basic set. The smaller binding energy value provides the higher reactivity of BCMTP compound than hydroxyl chloroquine and was corrected by high electrophilic and low nucleophilic reactions. The stability and charge delocalization of the molecule were also considered by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer which takes place within the molecule. Molecular electrostatic potential has also been analysed. Molecular docking studies are implemented to analyse the binding energy of the BCMTP compound against standard drugs such as the crystal structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES and SARS-CoV-2 main protease with an unliganded active site (2019-nCoV, corona virus disease 2019, COVID-19) and found to be considered having better antiviral agents. Molecular dynamics simulation was performed for COVID-19 main protease (Mpro: 6WCF/6Y84) to understand the elements governing the inhibitory effect and the stability of interaction under dynamic conditions.

Salen: Insight into the Crystal Structure, Hirshfeld Surface Analysis, Optical Properties, DFT, and Molecular Docking Studies

We report on a known Schiff base dye salen. The crystal structure of salen is in the enol–enol tautomer. Molecules are packed into a 3D supramolecular framework through C–H···π interactions. The absorption spectrum of salen in CH2Cl2 exhibits three bands in the UV region, while the spectrum in MeOH contains an additional band at 403 nm and a shoulder at 280 nm, corresponding to the cis-keto tautomer. The emission spectrum of salen in MeOH exhibits a band at 435 and 457 nm upon irradiation at 280 and 400 nm, respectively, arising from the enol–cis-keto* and/or cis-keto–cis-keto* tautomers. The solution of salen in CH2Cl2 showed dual emission with the bands at 349 and 462 nm upon irradiation at 290 nm with the low-energy emission band arising from the enol–cis-keto* and/or cis-keto–cis-keto* tautomers, while the high-energy band corresponds to the enol–enol* tautomer. The emission spectrum of salen in CH2Cl2 exhibits a single band at 464 nm upon irradiation at 380 nm, arising from the different conformers of the enol–cis-keto* and/or cis-keto–cis-keto* tautomers. The DFT calculations revealed that the enol–enol tautomer is the most favorable, followed by the enol–cis-keto tautomer. The global chemical reactivity descriptors were estimated from the HOMO and LUMO. The DFT calculations were also applied to probe salen as a potential corrosion inhibitor for some important metals used in implants. The enol–cis-keto and enol–trans-keto tautomers exhibit the best electron charge transfer from the molecule to the surface of all the studied metals, of which the most efficient electron charge transfer was established for Ni, Au, and Co. Molecular docking was applied to study interaction of tautomers of salen with a series of the SARS-CoV-2 proteins, of which the best binding affinity was found toward nsp14 (N7-MTase). © 2022 Taylor & Francis Group, LLC.

Structural and Molecular Packing study of Three New Amidophosphoric Acid Esters and Assessment of Their Inhibiting Activity Against SARS-CoV-2 by Molecular Docking.

Three new compounds of amidophosphoric acid esters with a [OCH2C(CH3)2CH2O]P(O)[X] segment (where X=cyclopentylamido (1), 2-aminopyridinyl (2) and pyrrolidinyl (3)) were synthesized and studied using FT-IR and 31P/13C/1H NMR spectroscopies and single-crystal X-ray diffraction analysis. The compounds crystallize in the triclinic space groups P 1 ‾ for 1 and 3 and in the orthorhombic space group Pca21 for 2, where the asymmetric unit consists of three symmetrically-independent molecules for 1 and one molecule for 2 and 3. The intermolecular interactions and supramolecular assemblies are assessed by Hirshfeld surface analysis and enrichment ratios. The results reveal that the substituent effect plays an important role in directing the supramolecular structures. The presence of the aromatic substituent aminopyridine in 2 providing the C-H…π interactions leads to a larger variety in interactions including H…H, H…O/O…H, H…C/C…H and H…N/N…H contacts, whereas the packings of the compounds 1 and 3 bearing aliphatic substituents only include H…H and H…O/O…H contacts. The enrichment ratios affirm the importance of O…H/H…O contacts reflecting the hydrogen bond N-H…O interactions to be the enriched contacts. Compounds 1-3 were also investigated along with five similar reported structures with a [OCH2C(CH3)2CH2O]P(O) segment for their inhibitory behavior against SARS-CoV-2. The molecular docking results illustrate that the presence of the aromatic amido substituent versus the aliphatic type provides a more favorable condition for their biological activities.

Structural-property relationship in halogen-bonded Schiff base derivative: Crystal structure, computational and SARS-CoV-2 docking

We synthesized the halogenated Schiff base compound to understand the influence of halogen and hydrogen bonding interactions. The Schiff base compound is characterized by FTIR, SEM-EDAX and single-crystal X-ray diffraction studies. The structural studies reveal that the 4-chloro-2-(((4-chlorobenzyl) imino) methyl) phenol crystallizes in the monoclinic, P 2 1 / n space group. The O1-H1 center dot center dot center dot N1 strong hydrogen bond forms the intramolecular pseudo chelating ring motif and acts as a coordinating site for metal complexes. The intra, intermolecular and 7r center dot center dot center dot 7r interactions were involved in the construction of supramolecular architecture. The interesting type-I halogen bonds having trans geometry are exhibited. Hirshfeld surface analysis supports the interactions observed in the crystal structure, and the energy framework analysis provides the stabilization interaction energy among the molecular pairs. The enrichment ratio provides favored contacts between the atomic pair and gives strong validation to the halogen center dot center dot center dot halogen and halogen center dot center dot center dot hydrogen bonds. The DFT studies give more insight into electronic structure and provide a global and local parameter of the molecule. NBO studies provide stabilization energy and charge transfer within the molecule. The QTAIM studies were used to calculate the strength of the halogen, hydrogen and stacking intermolecular interaction. Further, docking studies were carried out for COVID-19 proteins to reveal the structural-function properties of halogen and hydrogen bonds present in the synthesized compound.

Naphthalene-based bis-N-salicylidene aniline dyes: Crystal structures, Hirshfeld surface analysis, computational study and molecular docking with the SARS-CoV-2 proteins

In this work, we report structural and computational studies of a series of naphthalene-based bis-N-salicylidene aniline dyes, namely N,N′-bis-salicylidene-1,5-diaminonaphthalene (1), N,N′-bis(3-hydroxysalicylidene)-1,5-diaminonaphthalene (2) and N,N′-bis(3-methoxysalicylidene)-1,5-diaminonaphthalene (3). For 3, two polymorphs are known, namely 3red and 3yellow. Both polymorphs of 3 were analyzed and discussed. All the molecules adopt an enol-imine tautomer, stabilized by two intramolecular O–H⋯N hydrogen bonds. The structure of 2 is further stabilized by a couple of additional O–H⋯O hydrogen bonds and by intermolecular O–H⋯O interactions, yielding a 1D zig-zag supramolecular chain. Molecules of 2, 3red and 3yellow are interlinked through intermolecular C–H⋯π interactions, while the crystal packing of 1 and 2 is also described by intermolecular π⋯π interactions. More than 90% of the total Hirshfeld surface area for all the discussed molecules is occupied by H⋯H, H⋯C, H⋯O and C⋯C contacts. The polymorphs 3red and 3yellow, despite being chemically the same, differ geometrically, thus yielding remarkably different Hirshfeld surfaces. The Hirshfeld surface of 3yellow is very similar to that of 2. All structures are mainly characterized by the dispersion energy framework followed by the less significant electrostatic energy framework contribution. Molecular docking studies were employed to inspect the effect of 1–3 on the SARS-CoV-2 protein targets. The docking analysis revealed that the dye 2 showed the best binding energies toward Papain-like protease (PLpro, –10.40 kcal/mol), nonstructural protein 14 (nsp14 (N7-MTase), –10.10 kcal/mol), RdRp-RTP (–9.70 kcal/mol) and nonstructural protein 3 (nsp3_range 207-379-MES, –9.30 kcal/mol). The obtained results can give an insight into chemical and biological activities of the studied molecules that could aid in designing of potent reagents SARS-CoV-2.

Design, synthesis and characterization of novel Ni(II) and Cu(II) complexes as antivirus drug candidates against SARS-CoV-2 and HIV virus.

This paper describes the structure-based design, synthesis and anti-virus effect of two new coordination complexes, a Ni(II) complex [Ni(L)2] (1) and a Cu(II) complex [Cu(L)2] (2) of (E)-N-phenyl-2-(thiophen-2-ylmethylene) hydrazine-1-carbothioamide(HL). The synthesized ligand was coordinated to metal ions through the bidentate-N, S donor atoms. The newly synthesized complexes were characterized by various spectroscopic and physiochemical methods, powdered XRD analysis and also X-ray crystallography study. Ni(II) complex [Ni(L)2](1) crystallize in orthorhombic crystal system with the space group Pbca with four molecules in the unit cell (a = 9.857(3) Å, b = 7.749(2) Å, c = 32.292(10) Å, α = 90°, ß = 90°, γ = 90°, Z= 4) and reveals a distorted square planar geometry. A Hirshfeld surface and 2D fingerprint plot has been explored in the crystal structure of Ni(II) complex [Ni(L)2] (1). Energy framework computational analysia has also been explored. DFT based calculations have been performed on the Schiff base and its metal complexes to study the structure-property relationship. Furthermore, the molecular docking studies of the ligand and its metal complexes with SARS-CoV-2 virus (PDB ID: 7BZ5) and HIV-1 virus (PDB ID: 6MQA) are also investigated. The molecular docking calculations of the Ni(II) complex [Ni(L)2] (1) and a Cu(II) complex [Cu(L)2] (2) with SARS-CoV-2 virus revealed that the binding affinities at inhibition binding site of receptor protein are 9.7 kcal/mol and -9.3 kcal/mol, respectively. The molecular docking results showed that the binding affinities of Ni(II) complex (1) and Cu(II) complex (2) against SARS-CoV-2 virus were found comparatively higher than the HIV-1 virus (-8.5 kcal/mol and -8.2 kcal/mol, respectively). As potential drug candidates, Swiss-ADME predictions analyses are also studied and the results are compared with Chloroquine (CQ) and Hydroxychloroquine (HCQ) as anti-SARS-CoV-2 drugs.