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.

Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA.

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL¹) and X = Br (HL²)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL³) and 4-(p-fluorophenyl)thiosemicarbazone of salicylaldehyde (H2L4) and their copper(I) {[Cu(HL¹)(PPh3)2Br]·CH3CN (1) and [Cu(HL²)(PPh3)2Cl]·DMSO (2)} and copper(II) {[(Cu2L³2Cl)2(µ-Cl)2]·2H2O (3) and [Cu(L4)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and -cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 104 to 105 M⁻¹. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

Syntheses and structural investigation of some alkali metal ion-mediated LV(V)O2(-) (L(2-) = tridentate ONO ligands) species: DNA binding, photo-induced DNA cleavage and cytotoxic activities.

Eight alkali metal ion-mediated dioxidovanadium(v), [{V(V)O2L(1-6)}A(H2O)n]∝, complexes for A = Li(+), Na(+), K(+) and Cs(+), containing tridentate aroylhydrazonate ligands coordinating via ONO donor atoms, are described. All the synthesised ligands and the metal complexes were successfully characterised by elemental analysis, IR, UV-Vis and NMR spectroscopy. X-ray crystallographic investigation of 3, 5-7 shows the presence of distorted NO4 coordination geometries for LVO2(-) in each case, and varying µ-oxido and/or µ-aqua bridging with interesting variations correlated with the size of the alkali metal ions: with small Li(+), no bridging-O is found but four ion aggregates are found with Na(+), chains for K(+) and finally, layers for Cs(+). Two (5) or three-dimensional (3, 6 and 7) architectures are consolidated by hydrogen bonding. The dioxidovanadium(v) complexes were found to exhibit DNA binding activity due to their interaction with CT-DNA by the groove binding mode, with binding constants ranging from 10(3) to 10(4) M(-1). Complexes 1-8 were also tested for DNA nuclease activity against pUC19 plasmid DNA which showed that 6 and 7 had the best DNA binding and photonuclease activity; these results support their good protein binding and cleavage activity with binding constants ranging from 10(4) to 10(5) M(-1). Finally, the in vitro antiproliferative activity of all complexes was assayed against the HeLa cell line. Some of the complexes (2, 5, 6 and 7) show considerable activity compared to commonly used chemotherapeutic drugs. The variation in cytotoxicity of the complexes is influenced by the various functional groups attached to the aroylhydrazone derivative.

Highly stable hexacoordinated nonoxidovanadium(IV) complexes of sterically constrained ligands: syntheses, structure, and study of antiproliferative and insulin mimetic activity.

Three highly stable, hexacoordinated nonoxidovanadium(IV), V(IV)(L)2, complexes (1-3) have been isolated and structurally characterized with tridentate aroylhydrazonates containing ONO donor atoms. All the complexes are stable in the open air in the solid state as well as in solution, a phenomenon rarely observed in nonoxidovanadium(IV) complexes. The complexes have good solubility in organic solvents, permitting electrochemical and various spectroscopic investigations. The existence of nonoxidovanadium(IV) complexes was confirmed by elemental analysis, ESI mass spectroscopy, cyclic voltammetry, EPR, and magnetic susceptibility measurements. X-ray crystallography showed the N3O3 donor set to define a trigonal prismatic geometry in each case. All the complexes show in vitro insulin mimetic activity against insulin responsive L6 myoblast cells, with complex 3 being the most potent, which is comparable to insulin at the complex concentration of 4 µM, while the others have moderate insulin mimetic activity. In addition, the in vitro antiproliferative activity of complexes 1-3 against the HeLa cell line was assayed. The cytotoxicity of the complexes is affected by the various functional groups attached to the bezoylhydrazone derivative and 2 showed considerable antiproliferative activity compared to the most commonly used chemotherapeutic drugs.

Air oxygenation chemistry of 4-TBC catalyzed by chloro bridged dinuclear copper(II) complexes of pyrazole based tridentate ligands: synthesis, structure, magnetic and computational studies.

Four dinuclear bis(µ-Cl) bridged copper(II) complexes, [Cu(2)(µ-Cl)(2)(L(X))(2)](ClO(4))(2) (L(X) = N,N-bis[(3,5-dimethylpyrazole-1-yl)-methyl]benzylamine with X = H(1), OMe(2), Me(3) and Cl(4)), have been synthesized and characterized by the single crystal X-ray diffraction method. In these complexes, each copper(II) center is penta-coordinated with square-pyramidal geometry. In addition to the tridentate L(X) ligand, a chloride ion occupies the last position of the square plane. This chloride ion is also bonded to the neighboring Cu(II) site in its axial position forming an SP-I dinuclear Cu(II) unit that exhibits small intramolecular ferromagnetic interactions and supported by DFT calculations. The complexes 1-3 exhibit methylmonooxygenase (pMMO) behaviour and oxidise 4-tert-butylcatechol (4-TBCH(2)) with molecular oxygen in MeOH or MeCN to 4-tert-butyl-benzoquinone (4-TBQ), 5-methoxy-4-tert-butyl-benzoquinone (5-MeO-4-TBQ) as the major products along with 6,6'-Bu(t)-biphenyl-3,4,3',4'-tetraol and others as minor products. These are further confirmed by ESI- and FAB-mass analyses. A tentative catalytic cycle has been framed based on the mass spectral analysis of the products and DFT calculations on individual intermediates that are energetically feasible.

Bis(2,4-dinitro-phen-yl)sulfane.

In the title compound, C(12)H(6)N(4)O(8)S, the dinitro-phenyl rings subtend an angle of 78.46 (13) °. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds leading to the formation of a two-dimensional network lying parallel to the bc plane.

Methyl 2,2-bis-(2,4-dinitro-phen-yl)ethano-ate.

In the title compound, C(15)H(10)N(4)O(10), the dihedral angle between the aromatic rings is 89.05 (16)°. One O atom of one of the nitro groups is disordered over two sites in a 0.70:0.30 ratio. In the crystal, the mol-ecules are linked by weak C-H⋯O inter-actions.

Synthesis of a one-dimensional coordination polymer containing pendant hydrosulfide groups.

In view of the recent interest in compounds containing M-SH units, an organotin hydrosulfide compound, Me2Sn(SH)(O2CMe) (1) was prepared by controlled hydrolysis of the diorganotin thioacetate. Under similar mild hydrolytic conditions the corresponding benzoate could not be isolated. Instead, the thiobenzoate complex, Me2Sn(SOCPh)2 (3) was obtained in excellent yields indicating that there was no hydrolysis. Both 1 and 3 were characterized by X-ray crystallography. Some properties of the polymeric compound 1, such as spectral, electrical conductivity and NLO response were also studied. The reactivity and properties were explained using density functional calculations.

Ethyl 3-oxo-2-[(4-sulfamoylphen-yl)hydra-zono]butyrate.

In the title compound, C(12)H(15)N(3)O(5)S, an intra-molecular N-H⋯O hydrogen bond between the hydrazine unit and one of the carbonyl groups may influence the mol-ecular conformation. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds, including one which is bifurcated, link the mol-ecules into a two-dimensional network.

4-[2-(1-Acetyl-2-oxopropyl-idene)-hydrazino]-N-(pyrimidin-2-yl)benzene-sulfonamide.

In the title compound, C(15)H(15)N(5)O(4)S, the dihedral angle between the pyrimidine and benzene rings is 84.56 (2)°. Intra-molecular hydrazine-carbonyl N-H⋯O and inter-molecular sulfonamide-pyridimine N-H⋯N hydrogen bonds stabilize the mol-ecular and crystal structures, respectively.

X-ray crystal structure of phenylglycine hydrazide: synthesis and spectroscopic studies of its transition metal complexes.

Phenylglycine hydrazide was synthesized and investigated by X-ray crystallography. It crystallizes in the monoclinic space group P121/c with cell parameters a=5.9459 (18) Angstrom, b=5.1940 (16) Angstrom, c=26.7793 (83) Angstrom and Z=2. Its conformational changes, on complexation with transition metal ions Cu(II), Co(II), Ni(II), Mn(II) and Zn(II) has been studied on the basis of elemental analysis, magnetic moment and spectral (IR, (1)H NMR, UV-vis) studies. The bidentate nature of the ligand was confirmed on the basis of a comparative IR and NMR spectral studies. The trigonal bipyramidal geometries were observed for Cu(II), Ni(II) and Co(II) complexes, while it is octahedral for the remaining complexes. The conductivity data suggest them to be non-electrolytes.

t-3-Isopropyl-1-methyl-r-2,c-6-diphenylpiperidin-4-one thiosemicarbazone.

The piperidine ring in the title compound, C(22)H(28)N(4)S, exhibits a chair conformation. The thiosemicarbazone moiety adopts an extended conformation, and the planar phenyl rings are oriented equatorially with respect to the piperidine ring. Two intermolecular hydrogen bonds involving the S atom form molecular pairs, and the crystal structure is stabilized by weak C-H.pi interactions in addition to van der Waals forces.

Peptide-lanthanide interactions. Crystal structure of a europium(III)-triglycine complex.

Crystals of Eu-(Gly-Gly-Gly).(H2O)5.(ClO4)3 are triclinic, spacegroup P1 with a = 9.123 (2), b = 11.185 (5), c = 11.426 (2) A; alpha = 90.79 (2), beta = 98.08 (1), gamma = 98.57 (2) degrees; Z = 2. The europium cation is surrounded by four oxygens from three different peptide units and four oxygens from water molecules. The geometry around the metal is a distorted bi-capped trigonal prism. The peptide backbone conformation in this complex is compared with those in the free peptide and in various metal complexes. Considerable differences are observed between Eu(III) and Ca(II) complexes of triglycine.

Structure of methyl 5-phenyl-2-propionyl-3-pyrrolecarboxylate.

C15H15NO3, Mr = 257.4, monoclinic, P2(1)/n, a = 10.070 (2), b = 5.335 (3), c = 24.23 (1) A, beta = 91.60 (3) degrees, V = 1301 (2) A3, Z = 4, Dm (flotation) = 1.312 (3), Dx = 1.314 g cm-3, Cu K alpha (lambda = 1.5418 A), mu = 6.64 cm-1, F(000) = 544, T = 295 K, final R(F) = 0.037, wR = 0.035 for 850 significant reflections, I greater than or equal to 2.5 sigma(I). The phenyl ring and the pyrrole ring are planar, and the dihedral angle between them is 18.6 degrees. The nitrogen of the pyrrole ring exhibits N-H tautomerism and forms N-H...O type hydrogen bonds with the screw related carbonyl oxygen. In the unit cell the molecules form dimers across the centres of inversion and infinite spirals across the screw axis.

Structure of a 3 alpha-(D-methylglycoside) of 7,8 beta-epoxysinogenin--a cardioactive steroid.

C30H42O10, Mr = 562.66, orthorhombic, P2(1)2(1)2(1), a = 10.125 (1), b = 15.632 (2), c = 36.115 (4) A, V = 5716 (1) A3, Z = 8, Dm = 1.312 (2) (flotation), D chi = 1.308 g cm-3, Cu K alpha(lambda = 1.5418 A), mu = 7.18 cm-1, F(000) = 2416, T = 295 K. Final R(F) = 0.07 for 3348 significant reflections with I greater than or equal to 2.5 sigma(I). The A, B, C, D rings of the aglycone ring are found to be in cis-trans-cis fashion forming a buckled structure. The lactone is in C17 beta conformation. The molecules are stabilized by intermolecular hydrogen bonds. The longest direction of the steroid molecule is nearly parallel to the a axis. The conformational features exhibited by the molecule support proposals on activity.