Investigation of the molecular basis of halogenated Schiff base derivative by combined crystallographic and computational studies.

Halogenated Schiff base derivatives are gaining more popularity in supramolecular chemistry due to the synergistic effect of hydrogen and halogen-based noncovalent interactions, which helps to design novel therapeutic materials. In this work, we have examined the nature of molecular interactions to investigate the structure-functional relationship of a halogen-based derivative. The FTIR, HRMS and NMR spectroscopic techniques confirmed the formation of the desired novel Schiff base compound. Further, crystal structure studies showed an infinite 1D supramolecular chain formed by type-I halogen…halogen interaction. The Hirshfeld surface and enrichment ratio analyses were performed to visualize and assess the role of diverse interactions involved in crystal packing. The QTAIM, NCI, LOL and ELF studies were conducted extensively to comprehend the strength of interaction constructed based on electron density distribution. The global and local reactive indices were determined using DFT studies to analyze the molecular properties of the compound. Antibacterial activity against MRSA bacteria was performed and showed a good zone of inhibition. The docking analysis was performed for 1mwt protein and validated. The in silico molecular docking studies of the halogenated Schiff base structure with the penicillin-binding protein showed a good docking affinity of -7.5 kcal/mol and supported by in vitro studies. The ligand binding stability within the protein's active site was further demonstrated by molecular dynamics (MD) simulation studies for the Schiff base molecule.Communicated by Ramaswamy H. Sarma.

Perusal on the role of DMF solvent and hydrogen bonding in the formation of 1D polymeric chains in mixed ligand Ni(II) complex as an anticancer agent: a computational approach.

A novel mixed ligand Ni(II) metal complex has been investigated for the modification in structural conformation, coordination bond, and noncovalent interactions. The novel Ni(II) metal complex [Ni(TFPB)2(1,10-Ph)(DMF)] has been synthesized and structurally characterized, which featured six coordination with three bidentate ligands connected through oxygen and nitrogen atoms. The single-crystal X-ray analysis showed that the compound possessed octahedral geometry and C-H…F, C-H…O, and π…π intermolecular interactions resulting in the formation of supramolecular architecture contributed significantly towards the crystal packing and molecular stability. Hirshfeld surface analysis was carried out to validate various intermolecular interactions. Further, the 3D structural topologies were visualized using energy framework analysis. To explore the coordination stability and chemically reactive parameters of the novel Ni(II) complex, the electronic structure was optimized using density functional theory calculations. The natural bond orbital analysis revealed the various hyperconjugative interactions exhibited by the complex. In addition, the complex was screened for in silico studies to understand the antitumoricidal potential of the novel Ni(II) complex. Molecular docking studies were also performed against three targeted proteins (PDB ID: 6H0W, 6NE5, and 6E91) to investigate the binding mode and protein-ligand interactions. These results are further analyzed by molecular dynamic simulation to confirm the best possible interactions and stability in the active site of the targeted proteins with a simulation period of 100 ns.Communicated by Ramaswamy H. Sarma.

Nickel vanadate nitrogen-doped carbon nanocomposites for high-performance supercapacitor electrode.

A nickel-vanadium-based bimetallic precursor was produced using the polymerization process by urea-formaldehyde copolymers. The precursor was then calcined at 800 °C in an argon ambiance to form a Ni3V2O8-NC magnetic nanocomposite. Powerful techniques were used to study the physical characteristics and chemical composition of the fabricated Ni3V2O8-NC electrode. PXRD, Raman, and FTIR analyses proved that the crystal structure of Ni3V2O8-NC included N-doped graphitic carbon. FESEM and TEM analyses imaging showed the distribution of the Ni3V2O8 nanoparticles on the layered graphitic carbon structure. TEM images showed the prepared sample has a particle size of around 10-15 nm with an enhanced active site area of 146 m2/g, as demonstrated by BET analysis. Ni3V2O8-NC nanocomposite exhibits magnetic behaviors and a magnetization saturation value of 35.99 emu/g. The electrochemical (EC) studies of the synthesized Ni3V2O8-NC electrode proceeded in an EC workstation of three-electrode. In a 5 M potassium hydroxide as an electrolyte, the cyclic voltmeter exhibited an enhanced capacitance (CS) of 915 F/g at 50 mV/s. Galvanic charge-discharge (GCD) study also exhibited a superior capacitive improvement of 1045 F/g at a current density (It) of 10 A/g. Moreover, the fabricated Ni3V2O8-NC nanocomposite displays a good power density (Pt) of 356.67 W/kg, improved ion accessibility, and substantial charge storage. At the high energy density (Et) of 67.34 W h/kg, the obtained Pt was 285.17 W/kg. The enhanced GCD rate, cycle stability, and Et of the Ni3V2O8-NC magnetic nanocomposite nominate the sample as an excellent supercapacitor electrode. This study paves the way for developing effective, efficient, affordable, and ecologically friendly electrode materials.

Design, crystal structure determination, molecular dynamic simulation and MMGBSA calculations of novel p38-alpha MAPK inhibitors for combating Alzheimer's disease.

The hallmark of the Alzheimer's disease (AD) is the accumulation of aggregated, misfolded proteins. The cause for this accumulation is increased production of misfolded proteins and impaired clearance of them. Amyloid aggregation and tau hyperphosphorylation are the two proteinopathies which accomplish deprivation of cell and tissue hemostasis during neuropathological process of the AD, as a result of which progressive neuronal degeneration and the loss of cognitive functions. p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in both the events associated with AD: tau protein phosphorylation and inflammation. p38α MAPK pathway is activated by a dual phosphorylation at Thr180 and Tyr182 residues. Clinical and preclinical evidence implicates the stress related kinase p38α MAPK as a potential neurotherapeutic target. Drug design of p38α MAPK inhibitors is mainly focused on small molecules that compete for Adenosine triphosphate in the catalytic site. Here we have carried out the synthesis of phenyl sulfonamide derivatives Sulfo (I) and Sulfo (II). Crystal structures of Sulfo (I) and Sulfo (II) were solved by direct methods using SHELXS-97. Sulfo (I) and Sulfo (II) have Rint values of 0.0283 and 0.0660, respectively, indicating good quality of crystals and investigated their ability against p38α MAPK. Docking studies revealed that the Sulfo (I) had better binding affinity (-62.24 kcal/mol) as compared to Sulfo (II) and cocrystal having binding affinity of -54.61 kcal/mol and -59.84 kcal/mol, respectively. Molecular dynamics simulation studies of Sulfo (I) and cocrystal of p38α MAPK suggest that during the course of 30 ns simulation run, compound Sulfo (I) attained stability, substantiating the consistency of its binding to p38α MAPK compared to cocrystal. Binding free energy analysis suggests that the compound Sulfo (I) is better than the cocrystal. Thus, this study corroborates the therapeutic potential of synthesized Sulfo (I) in combatting AD.Communicated by Ramaswamy H. Sarma.

4-acetamido-3-nitrobenzoic acid - structural, quantum chemical studies, ADMET and molecular docking studies of SARS-CoV2.

In December 2019, a new type of SARS corona virus emerged from China and caused a globally pandemic corona virus disease (COVID-19). This highly infectious virus has been named as SARS-CoV-2 by the International Committee of the Taxonomy of Viruses. It has severely affected a large population and economy worldwide. Globally various scientific communities have been involved in studying this newly emerged virus and is lifecycle. Multiple diverse studies are in progress to design novel therapeutic agents, in which understanding of interactions between the target and drug ligand is a significant key for this challenge. Structures of proteins involved in the life cycle of the virus have been revealed in RCSB PDB by researchers. In this study, we employed molecular docking study of 4-Acetamido-3-nitrobenzoic acid (ANBA) with corona virus proteins (spike protein, spike binding domain with ACE2 receptor and Main protease, RNA-dependent RNA polymerase). Single crystal X-ray analysis and density functional theory calculations were carried out for ANBA to explore the structural and chemical-reactive parameters. Intermolecular interactions which are involved in the ligand-protein binding process are validated by Hirshfeld surface analysis. To study the behaviour of ANBA in a living organism and to calculate the physicochemical parameters, ADMET analysis was done using SwissADME and Osiris data warrior tools. Further, Toxicity of ANBA was predicted using pkCSM online software. Based on the molecular docking analysis, we introduce here a potent drug molecule that binds to the COVID-19 proteins.Communicated by Ramaswamy H. Sarma.

Structure-property relationship in thioxotriaza-spiro derivative: Crystal structure and molecular docking analysis against SARS-CoV-2 main protease.

Detailed structural and non-covalent interactions in thioxotriaza-spiroderivative (DZ2) are investigated by single crystal structure anslysis and computational approaches. Its results were compared with the previously reported spiroderivative (DZ1). The crystal structure analysis revealed various C-H…O, N-H…O, C-H…N and N-H…S hydrogen bonds involved in constructing several dimeric motifs to stabilize the crystal packing. The differences and similarities in the relative contribution of non-covalent interactions in DZ1 and DZ2 compounds are compared using the Hirshfeld surface analysis and 2D fingerprint plots. The binding energies of specific molecular pairs and homodimers have been obtained using molecule-molecule interaction energy calculation. The hierarchy and topology of pair-wise intermolecular interactions are visualized through energy frameworks. The nature and strength of intra and intermolecular interactions were characterized using non-covalent interaction index analysis and the quantum theory of atoms in molecule approach. Further, molecular docking of compounds (DZ1 and DZ2) with SARS-CoV-2 main protease for COVID-19 is performed. And the superposition of these ligands and inhibitor N3, which is docked into the binding pocket of 7BQY, is presented. The binding affinity of -6.7 kcal/mol is observed, attributed to hydrogen bonding and hydrophobic interactions between the ligand and the amino acid residues of the receptor.

Generation, characterization and molecular binding mechanism of novel dipeptidyl peptidase-4 inhibitory peptides from sorghum bicolor seed protein.

Food proteins and their constituent peptides impart huge health benefits besides their nutritional attributes. Sorghum bicolor protein hydrolysates (SPH) and derived bioactive peptides generated by simulated gastrointestinal digestion were studied for DPP-4 inhibitory properties using in vitro and in situ assays. Identified peptides, LSICGEESFGTGSDHIR (PEP1), SLGESLLQEDVEAHK (PEP2) and QLRDIVDK (PEP4) displayed potent DPP-4 inhibition with IC50 values of 73.5, 82.5 and 8.55 µM respectively. DPP-4 inhibition mechanism by the peptides was investigated by DPP4-peptide inhibition kinetics, molecular docking and microscale thermophoresis binding studies. The peptides bound to DPP-4 with micromolar affinities and PEP4 showed significantly increased affinity. The mixed type enzyme inhibition by peptides suggested that the peptides either block the active site of DPP-4 or changes the enzyme conformation via a secondary binding site. Overall, the results demonstrate that sorghum seeds are an adequate source of peptides with DPP-4 inhibitory properties that could be used in functional food formulations.

Erratum: (E)-3-(3-Methyl-thio-phen-2-yl)-1-p-tolyl-prop-2-en-1-one. Corrigendum.

[This corrects the article DOI: 10.1107/S2414314617002346.].

I2-Catalyzed transformation of o-aminobenzamide to o-ureidobenzonitrile using isothiocyanates.

The present work describes an unexpected and unique protocol for the iodine catalysed synthesis of o-ureidobenzonitriles using o-aminobenzamides and isothiocyanates via intramolecular rearrangement. The metal-free route achieved here is insensitive to moisture and applicable to the synthesis of a wide variety of o-ureidobenzonitriles with excellent yields even in a scalable fashion.

Corrigendum: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents.

[This corrects the article DOI: 10.3389/fchem.2019.00474.].

N-[2-(Tri-fluoro-meth-yl)phen-yl]maleamic acid: crystal structure and Hirshfeld surface analysis.

The title mol-ecule, C11H8F3NO3, adopts a cis configuration across the -C=C- double bond in the side chain and the dihedral angle between the phenyl ring and side chain is 47.35 (1)°. The -COOH group adopts a syn conformation (O=C-O-H = 0°), unlike the anti conformation observed in related maleamic acids. In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds are connected via N-H⋯O hydrogen bonds and C-H⋯O inter-actions into (100) sheets, which are cross-linked by another C-H⋯O inter-action to result in a three-dimensional network. The Hirshfeld surface fingerprint plots show that the highest contribution to surface contacts arises from O⋯H/H⋯O contacts (26.5%) followed by H⋯F/F⋯H (23.4%) and H⋯H (17.3%).

Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents.

Prostate Cancer (PCa) is the most frequently diagnosed cancer in men in their late '50s. PCa growth is mainly due to the activation of the androgen receptor by androgens. The treatment for PCa may involve surgery, hormonal therapy, and oral chemotherapeutic drugs. A structural based molecular docking approach revealed the findings of (E)-N'-((1-chloro-3,4-dihydronaphthalen-2-yl)methylene)benzohydrazide derivatives, where the possible binding modes of the compounds with protein (PDB ID: 3V49) are shown. The compounds (6a-k) were synthesized and characterized by using conventional methods. The compounds, 6g, 6j, and 6k were reconfirmed through single crystal X-ray diffraction (XRD). Further, the compounds (6a-k) and standard drug were evaluated against human prostate cancer cell lines, LNCaP and PC-3 and the non-cancerous cell line, 3T3. Among these compounds, 6g and 6j showed higher cytotoxicity, and 6g exhibited dose-dependent activity and reduced cell viability. The mechanism of action was observed through the induced apoptosis and was further confirmed by western blot and ELISA. Molecular dynamics simulation studies were carried out to calculate the interaction and the stability of the protein-ligand complex in motion. ADME properties were predicted for all the tested compounds. These findings may give vital information for further development.

Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents.

Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.

Synthesis, mol-ecular structure and Hirshfeld surface analysis of (4-meth-oxy-phen-yl)[2-(methyl-sulfan-yl)thio-phen-3-yl]methanone.

The title compound, C13H12O2S2, crystallizes in the triclinic space group P . The mol-ecular structure is substanti-ally twisted, with a dihedral angle of 43.70 (2)° between the 2-(methyl-sulfan-yl)thio-phene and 4-meth-oxy-phenyl rings. In the crystal, mol-ecules are linked through C-H⋯O inter-actions and form a bifurcated layer stacking along the b-axis direction and enclosing R 2 2(10) ring motifs. The phenyl rings are involved in π-π inter-actions with a centroid-centroid separation of 3.760 (2) Å. The Hirshfeld surfaces were studied and the contributions of the various inter-molecular inter-actions were qu-anti-fied.

Crystal structures of 2-amino-pyridine citric acid salts: C5H7N2+·C6H7O7- and 3C5H7N2+·C6H5O73.

2-Amino-pyridine and citric acid mixed in 1:1 and 3:1 ratios in ethanol yielded crystals of two 2-amino-pyridinium citrate salts, viz. C5H7N2+·C6H7O7- (I) (systematic name: 2-amino-pyridin-1-ium 3-carb-oxy-2-carb-oxy-methyl-2-hy-droxy-propano-ate), and 3C5H7N2+·C6H5O73- (II) [systematic name: tris-(2-amino-pyridin-1-ium) 2-hy-droxy-propane-1,2,3-tri-carboxyl-ate]. The supra-molecular synthons present are analysed and their effect upon the crystal packing is presented in the context of crystal engineering. Salt I is formed by the protonation of the pyridine N atom and deprotonation of the central carb-oxy-lic group of citric acid, while in II all three carb-oxy-lic groups of the acid are deprotonated and the charges are compensated for by three 2-amino-pyridinium cations. In both structures, a complex supra-molecular three-dimensional architecture is formed. In I, the supra-molecular aggregation results from Namino-H⋯Oacid, Oacid⋯H-Oacid, Oalcohol-H⋯Oacid, Namino-H⋯Oalcohol, Npy-H⋯Oalcohol and Car-H⋯Oacid inter-actions. The mol-ecular conformation of the citrate ion (CA3-) in II is stabilized by an intra-molecular Oalcohol-H⋯Oacid hydrogen bond that encloses an S(6) ring motif. The complex three-dimensional structure of II features Namino-H⋯Oacid, Npy-H⋯Oacid and several Car-H⋯Oacid hydrogen bonds. In the crystal of I, the common charge-assisted 2-amino-pyridinium-carboxyl-ate heterosynthon exhibited in many 2-amino-pyridinium carboxyl-ates is not observed, instead chains of N-H⋯O hydrogen bonds and hetero O-H⋯O dimers are formed. In the crystal of II, the 2-amino-pyridinium-carboxyl-ate heterosynthon is sustained, while hetero O-H⋯O dimers are not observed. The crystal structures of both salts display a variety of hydrogen bonds as almost all of the hydrogen-bond donors and acceptors present are involved in hydrogen bonding.

Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii.

Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Šusing X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.

Different supramolecular architectures mediated by different weak interactions in the crystals of three N-aryl-2,5-dimethoxybenzenesulfonamides.

The synthesis and evaluation of the pharmacological activities of molecules containing the sulfonamide moiety have attracted interest as these compounds are important pharmacophores. The crystal structures of three closely related N-aryl-2,5-dimethoxybenzenesulfonamides, namely N-(2,3-dichlorophenyl)-2,5-dimethoxybenzenesulfonamide, C14H13Cl2NO4S, (I), N-(2,4-dichlorophenyl)-2,5-dimethoxybenzenesulfonamide, C14H13Cl2NO4S, (II), and N-(2,4-dimethylphenyl)-2,5-dimethoxybenzenesulfonamide, C16H19NO4S, (III), are described. The asymmetric unit of (I) consists of two symmetry-independent molecules, while those of (II) and (III) contain one molecule each. The molecular conformations are stabilized by different intramolecular interactions, viz. C-H...O interactions in (I), N-H...Cl and C-H...O interactions in (II), and C-H...O interactions in (III). The crystals of the three compounds display different supramolecular architectures built by various weak intermolecular interactions of the types C-H...O, C-H...Cl, C-H...π(aryl), π(aryl)-π(aryl) and Cl...Cl. A detailed Hirshfeld surface analysis of these compounds has also been conducted in order to understand the relationship between the crystal structures. The dnorm and shape-index surfaces of (I)-(III) support the presence of various intermolecular interactions in the three structures. Analysis of the fingerprint plots reveals that the greatest contribution to the Hirshfeld surfaces is from H...H contacts, followed by H...O/O...H contacts. In addition, comparisons are made with the structures of some related compounds. Putative N-H...O hydrogen bonds are observed in 29 of the 30 reported structures, wherein the N-H...O hydrogen bonds form either C(4) chain motifs or R22(8) rings. Further comparison reveals that the characteristics of the N-H...O hydrogen-bond motifs, the presence of other interactions and the resultant supramolecular architecture is largely decided by the position of the substituents on the benzenesulfonyl ring, with the nature and position of the substituents on the aniline ring exerting little effect. On the other hand, the crystal structures of (I)-(III) display several weak interactions other than the common N-H...O hydrogen bonds, resulting in supramolecular architectures varying from one- to three-dimensional depending on the nature and position of the substituents on the aniline ring.

A fluorophore-labelled copper complex: crystal structure, hybrid cyclic water-perchlorate cluster and biological properties.

A fluorophore-labelled copper(II) complex, aquabis(dimethylformamide-κO)(perchlorato-κO)[2-(quinolin-2-yl)-1,3-oxazolo[4,5-f][1,10]phenanthroline]copper(II) perchlorate monohydrate, [Cu(ClO4)(C22H12N4O)(C3H7NO)2(H2O)]ClO4·H2O, has been synthesized and characterized. A cyclic hydrogen-bonded water-perchlorate anionic cluster, i.e. [(ClO4)2(H2O)2]2-, has been identified within the structure. Each cyclic anionic cluster unit is interconnected by hydrogen bonding to the cation. The cations join into an infinite hydrogen-bonded chain running in the [010] direction. Furthermore, interaction of the complex with calf-thymus DNA (CT-DNA) and cellular localization within the cells was explored. Spectroscopic studies indicate that the compound has a good affinity for DNA and stains the nucleus of the cells.

Synthesis, structural characterization and biological properties of phosphorescent iridium(III) complexes.

Two phosphorescent cyclometalated iridium(III)-triptycenyl-1,10-phenanthroline complexes [Ir(ppy)2(tpt-phen)]+ (1) and [Ir(bhq)2(tpt-phen)]+ (2) {ppy=2-phenylpyridine, bhq=Benzo[h]quinoline, tpt-phen=triptycenyl-1,10-phenanthroline} have been synthesized and structurally characterized. The structure of complex 2 has been studied by single crystal X-ray crystallography. The photophysical properties of complexes in a different solvent have also been investigated. The binding of complexes to the double stranded calf thymus (CT-DNA) has been investigated by spectroscopic techniques. These complexes condense originally circular plasmid DNA into particulate structures. The DNA-condensation induced by these complexes have been investigated by electrophoretic mobilty shift assay, dynamic light scattering, and fluorescence microscopy. Furthermore, the cytotoxicity of these complexes towards HeLa cells have been studied and their cellular localisation properties have been investigated by fluorescence microscopy.

The crystal structure of zwitterionic 2-{[(4-imin-iumyl-3-methyl-1,4-di-hydro-pyridin-1-yl)meth-yl]carbamo-yl}benzoate hemihydrate.

The asymmetric unit of the title compound, C15H15N3O3·0.5H2O, comprises two 2-{[(4-iminiumyl-3-methyl-1,4-di-hydro-pyridin-1-yl)meth-yl]carbamo-yl}benzoate zwitterions (A and B) and a water mol-ecule. The dihedral angles between the pyridine and phenyl rings in the zwitterions are 53.69 (10) and 73.56 (11)° in A and B, respectively. In the crystal, mol-ecules are linked by N-H⋯O, O-H⋯O, C-H⋯O and C-H⋯π(ring) hydrogen bonds into a three-dimensional network. The crystal structure also features π-π inter-actions involving the centroids of the pyridine and phenyl rings [centroid-centroid distances = 3.5618 (12) Šin A and 3.8182 (14) Šin B].