Spectroscopic, crystal structure and DFT-assisted studies of some nickel(II) chelates of a heterocyclic-based NNO donor aroylhydrazone: in vitro DNA binding and docking studies.

Five new nickel(II) complexes have been synthesised with an NNO donor tridentate aroylhydrazone (HFPB) employing the chloride, nitrate, acetate and perchlorate salts, and all the complexes are physiochemically characterized. Elemental analyses suggested stoichiometries as Ni(FPB)(NO3)]·2H2O (1), [Ni(HFPB)(FPB)]Cl (2), [Ni(FPB)(OAc)(DMF)] (3), [Ni(FPB)(ClO4)]·DMF (4), [Ni(FPB)2] (5). Aroylhydrazone is found coordinating in deprotonated iminolate form in four of the complexes (1, 3, 4, 5) however in one case (complex 2), two aroylhydrazone moieties are binding to the metal centre in the neutral and anionic forms. The structure of the bisligated complex 5, found using single crystal X ray diffraction studies confirmed that the metal has a distorted octahedral N4O2 coordination environment, with each of the two deprotonated ligands coordinating through the pyridine nitrogen, imino-hydrazone nitrogen and the enolate oxygen of the hydrazone moiety. To compare and study, the electronic interactions and stabilities of the metal complexes, various quantum chemical parameters were calculated. Moreover, Hirshfeld surface analysis was carried out for complex 5 to determine the intermolecular interactions. The biophysical attributes of the ligand and complex 5 have been investigated with CT-DNA and experimental outcomes show that the Ni(II) complex exhibited higher binding propensity towards DNA as compared to ligand. Furthermore, to specifically understand the type of interactions of the metal complexes with DNA, molecular docking studies were effectuated. In addition, the electronic and related reactivity behaviors of the ligand and five Ni(II) complexes were studied using B3LYP/6-31 + + G**/LANL2DZ level. As expected, the obtained results from Natural Bond Orbital (NBO) computations displayed that the resonance interactions (n → π* and π → π*) play a determinant role in evaluating the chemical attributes of the reported compounds.

A novel manganese(II) bisthiocarbohydrazone complex: Crystal structures, Hirshfeld surface analysis, DFT and molecular docking study with SARS-CoV-2.

A novel Mn(II) complex [Mn(H2L)Cl2]•H2O (1) of a ditopic ligand 1,5-bis(2-benzoylpyridine) thiocarbohydrazone (H2L) was synthesized and characterised physico-chemically. A part of the mother solution of the complex 1 and THF yielded single crystals in a triclinic space group and are found same from the crystals obtained from another mixture of the mother solution and ethyl acetate. Single crystal XRD studies have confirmed the mononuclear complex formation and absence of any interactions between the Mn(II) centers. A solution of the complex 1 in chloroform, conversely, yielded a crystallographically different complex [Mn(H2L)Cl2]•CHCl3 (1a) in monoclinic and is also characterised with single crystal XRD. The ligand is coordinated through thione sulfur atom to form a square pyramidal geometry around Mn(II) center in both the complexes. The molecular packing of the complexes is found influenced by the nature of solvent inclusion, and are stabilized by different non-covalent interactions in the lattice. The intermolecular interactions are quantified by Hirshfeld surface analyses, which reveal that H•••Cl interactions has maximum contribution to the total Hirshfeld surface in the complex 1a. This is the first crystal structure study of a manganese(II) complex of a bisthiocarbohydrazone ligand. The molecular and electronic structures of the complexes are studied by DFT quantum chemical calculations. The band gap (Eg) of the complex 1 was estimated as 2.45 eV using Kubelka-Munk model and is in agreement with the electronic spectral calculations of the complex at TD-DFT level. Molecular docking studies of both the ligand and the complex reveal their greater propensity towards SARS-CoV-2 main protease compared to B-DNA dodecamer. Also, the binding potential of the ligand and the complex with SARS-CoV-2 main protease is found higher than that with chloroquine and hydroxychloroquine.

Molecular trail for the anticancer behavior of a novel copper carbohydrazone complex in BRCA1 mutated breast cancer.

Novel chelated metal complexes were synthesized from carbohydrazones to thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild-type and mutated breast cancer cells: MCF-7 (BRCA1+ /ER+ ), MDA-MB-231 (BRCA1+ /ERα- ), HCC-1937 (BRCA1- /ERα- ), HCC1937/wt BRCA1, MX1 (BRCA1- /ERα- ), and MDA-MB-436 (BRCA1- /ERα- ) were screened for anti-cancer activity. Cu2 (HL)(HSO4 ) · H2 O]SO4 · 6 H2 O (CS2) is the most potent anticancer agent among the copper carbohydrazone and thiocarbohydrazone complexes analyzed in this study. It can be suggested that the presence of sulphate, as pharmacologically active centre, can induce cytotoxicity more effectively when compared to chlorine, bromine, perchlorate, and methanol. This is the first report demonstrating that CS2 can bind to DNA by hindering BamH1 activity and could induce DNA double strand breaks as evidenced by γ-H2AX expression. In addition to this, CS2 could also act as a Topo II inhibitor at a much lower concentration than etoposide and induce apoptosis, making it a potent anticancer agent. In combination with Pb, a potent ROS inducer, CS2 could induce synergistic anti-cancer activity in HR/ BRCA1 defective breast cancer cells. This is the first study reporting the mechanism involved in the induction of apoptosis for a metal chelated copper carbohydrazone complex and its combination effects with Pb in HR defective, BRCA1 mutated breast cancer cells.

Crystal structures of (1E,4E)-1,5-bis-(5-bromo-thio-phen-2-yl)-2,4-di-methyl-penta-1,4-dien-3-one and (E)-4-(5-bromo-thio-phen-2-yl)-1,3-di-phenyl-but-3-en-2-one.

The title compounds, C15H12Br2OS2, (I), and C20H15BrOS, (II), were synthesized by employing Claisen-Schmidt condensation of pentan-3-one and di-benzyl-acetone with 5-bromo-thio-phene-2-carbaldehyde in the presence of methano-lic KOH. Even though 1:2 products were expected in both of the reactions, 1:2 and 1:1 products were obtained as (I) and (II), respectively. In (I), the two methyl groups are trans to each other, 29.5 (7) and 28.7 (7)° away from the central carbonyl bond between them, whereas the two phenyl rings of di-benzyl-acetone subtend a dihedral angle of 53.09 (18)°. In the crystal of (I), C-H⋯O hydrogen bonds define mol-ecular chains along c. A second type of mol-ecular chain is formed along b by means of C-Br⋯π inter-actions. These two families of mol-ecular chains are stacked by π-π inter-actions, forming a three-dimensional supra-molecular architecture. In (II), similar C-H⋯O hydrogen bonds as in (I) define inversion dimers, whilst C-H⋯.π inter-actions build a staircase structure along the a axis.

Crystal structure of N'-[(E)-3,5-di-chloro-2-hy-droxy-benzyl-idene]-4-nitro-benzo-hydrazide di-methyl-formamide monosolvate.

In the title compound, C14H9Cl2N3O4·C3H7NO, the hydrazone mol-ecule adopts an E conformation with respect to azomethine bond, and the dihedral angle between the two aromatic rings [8.96 (11)°] shows that the rings are almost co-planar. The planar conformation of the mol-ecule is stabilized by the intra-molecular O-H⋯N hydrogen bond involving the OH group and azomethine N atom. The azomethine and keto bond distances [1.269 (2) and 1.210 (2) Å, respectively] are very close to the formal C=N and C=O bond lengths. The di-methyl-formamide solvent mol-ecule is connected to the hydrazone NH group via an N-H⋯O hydrogen bond. In the crystal, non-classical C-H⋯O and C-H⋯Cl hydrogen bonds link the mol-ecules into chains along [322]. A supra-molecular three-dimensional architecture is created by weak C-Cl⋯π [4.163 (3) Å, 83.26 (9)°] and π-π [centroid-centroid distance = 4.0395 (14) Å] inter-actions.

Crystal structure of (E)-N'-(5-bromo-2-hy-droxy-benzyl-idene)nicotinohydrazide monohydrate.

In the title compound, C13H10BrN3O2·H2O, the conformation about the azomethine double bond is E. The mol-ecule exists in the amido form with a C=O bond length of 1.229 (2) Å. There is an intra-molecular O-H⋯N hydrogen bond forming an S(6) ring motif. The whole mol-ecule is almost planar, with an r.m.s. deviation of 0.021 Šfor all non-H atoms, and the dihedral angle between the planes of the pyridine and benzene rings is 0.74 (12)°. In the crystal, the water mol-ecule of crystallization links the organic mol-ecules via Ow-H⋯O, Ow-H⋯N and N-H⋯Ow hydrogen bonds and short C-H⋯Ow contacts, forming sheets lying parallel to (100). Within the sheets there is a weak π-π inter-action involving the pyridine and benzene rings [centroid-to-centroid distance = 3.8473 (15) Å]. The sheets are linked via C-H⋯Br inter-actions, forming a three-dimensional network.

Crystal structure of (E)-2-[(2-hy-droxy-4-meth-oxy-phen-yl)(phen-yl)methyl-idene]-N-phenyl-hydrazine-1-carboxamide.

The title compound, C21H19N3O3, has an E conformation about the azomethine double bond. The central moiety of the hydrazinecarboxamide moiety [-N-N-C(=O)-N-] has an almost coplanar arrangement [maximum deviation for the C atom = 0.010 (2) Å]. This central moiety is flanked by three aromatic rings and its mean plane makes dihedral angles of 24.7 (1), 72.91 (12) and 34.26 (11) Å, respectively, with the phenolic ring, the phenyl ring attached to the same C atom as the phenolic ring, and the phenyl-hydrazine ring. The adjacent phenolic and phenyl rings are twisted away from each other to reduce steric hindrance and make a dihedral angle of 80.59 (12)°. The phenolic and phenyl-hydrazine rings are inclined to one another by 28.89 (11)°. The rigidity of the mol-ecule is increased by an intra-molecular O-H⋯N hydrogen bond involving the phenolic hydrogen and the azomethine N atom. In the crystal, the carbonyl O atom forms bifurcated hydrogen bonds with the two NH atoms of the hydrazinic group, leading to the formation of chains propagating along [001]. Within the chains there are also C-H⋯O hydrogen bonds present. The chains are linked via C=O⋯π [3.4316 (18) Å] and parallel slipped π-π inter-actions, involving inversion-related benzene rings [centroid-centroid distance = 3.8850 (14) Å; inter-planar distance = 3.3895 (10) Å; slippage = 1.899 Å], forming sheets lying parallel to (100).

Crystal structure of aqua-[(E)-N'-(5-bromo-2-oxido-benzyl-idene-κO)benzohydrazidato-κ(2) O,N']dioxidomolybdenum(VI) di-methyl-formamide monosolvate.

The title compound, [Mo(C14H9BrN2O2)O2(H2O)]·C3H7NO, has a distorted octa-hedral geometry around the Mo atom, with the two terminal oxide groups lying cis to each other. The two aromatic rings present in the mol-ecule are almost coplanar, forming a dihedral angle of 1.4 (2)°. The five-membered ring involving the metal atom is puckered, with an amplitude Q = 0.358 (2) Šand ϕ = 204.1 (6)°. In the crystal, pairs of inversion-related mol-ecules are linked by O-H⋯N hydrogen bonds. An O-H⋯O hydrogen bond connects the water ligand to the di-methyl-formamide solvent mol-ecule. The crystal packing also features π-π [centroid-centroid distance of 3.688 (2) Å] and C-H⋯O inter-actions.

Crystal structure of 4-{(E)-[2-(pyridin-4-ylcarbon-yl)hydrazin-1-yl-idene]meth-yl}phenyl acetate monohydrate.

The asymmetric unit of the title compound, C15H13N3O3·H2O, comprises a 4-{(E)-[2-(pyridin-4-ylcarbon-yl)hydrazinyl-idene]meth-yl}phenyl acetate mol-ecule and a solvent water mol-ecule linked by O-H⋯O and O-H⋯N hydrogen bonds from the water mol-ecule and a C-H⋯O contact from the organic mol-ecule. The compound adopts an E conformation with respect to the azomethine bond and the dihedral angle between the pyridine and benzene rings is 21.90 (7)°. The azomethine bond [1.275 (2) Å] distance is very close to the formal C=N bond length, which confirms the azomethine bond formation. An extensive set of O-H⋯O, O-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds builds a two-dimensional network progressing along the c axis.

Crystal structure of 8-[7,8-bis-(4-chloro-benzo-yl)-7H-cyclo-penta-[a]ace-naphthylen-9-yl]naphthalene-1-carb-oxy-lic acid.

The title compound, C40H22Cl2O4, was formed by a Michael-Aldol domino reaction sequence, which coupled acenaphthene-quinone with 4-chloro-aceto-phenone in the presence of KOH in methanol. The dihedral angles between the central cyclo-penta-[a]ace-naphthyl-ene fused-ring system (r.m.s. deviation = 0.066 Å) and the 4-chloro-benzoyl rings are 62.25 (10) and 70.19 (10)°. The dihedral angle between the central ring system and the naphthoic acid grouping is 62.46 (7)°. This twisting of the pendant rings facilitates the formation of an intra-molecular aromatic π-π stacking inter-action between the 4-chloro-benzoyl and naphthoic acid rings, with centroid-centroid distances of 3.4533 (16) and 3.5311 (16) Å, and a C-H⋯π inter-action between one of the H atoms of the central moiety and the 4-chloro-benzoyl ring with an H⋯π distance of 2.57 Å. In the crystal, carb-oxy-lic acid inversion dimers generate R 2 (2)(8) loops. The dimers are linked by weak C-H⋯O and C-H⋯Cl hydrogen bonds and C-H⋯π inter-actions, generating a three-dimensional architecture.

Synthesis and spectral characterization of mono- and binuclear copper(II) complexes derived from 2-benzoylpyridine-N4-methyl-3-thiosemicarbazone: crystal structure of a novel sulfur bridged copper(II) box-dimer.

Mononuclear and binuclear copper(II) complexes of 2-benzoylpyridine-N(4)-methyl thiosemicarbazone (HL) were prepared and characterized by a variety of spectroscopic techniques. Structural evidence for the novel sulfur bridged copper(II) iodo binuclear complex is obtained by single crystal X-ray diffraction analysis. The complex [Cu2L2I2], a non-centrosymmetric box dimer, crystallizes in monoclinic C2/c space group and it was found to have distorted square pyramidal geometry (Addison parameter, τ=0.238) with the square basal plane occupied by the thiosemicarbazone moiety and iodine atom whereas the sulfur atom from the other coordinated thiosemicarbazone moiety occupies the apical position. This is the first crystallographically studied system having non-centrosymmetrical entities bridged via thiolate S atoms with Cu(II)I bond. The tridentate thiosemicarbazone coordinates in mono deprotonated thionic tautomeric form in all complexes except in sulfato complex, [Cu(HL)(SO4)]·H2O (1) where it binds to the metal centre in neutral form. The magnetic moment values and the EPR spectral studies reflect the binuclearity of some of the complexes. The spin Hamiltonian and bonding parameters are calculated based on EPR studies. In all the complexes g||>g⊥>2.0023 and the g values in frozen DMF are consistent with the d(x2-y2) ground state. The thermal stabilities of some of the complexes were also determined.

Crystal structure of (4-chloro-phen-yl)[2-(10-hy-droxy-phenanthren-9-yl)phenanthro[9,10-b]furan-3-yl]methanone.

In the title compound, C37H21ClO3, the dihedral angle between the two phenanthrene moieties is 57.79 (5)°. The furan and one of the phenanthrene groups are fused in an almost coplanar arrangement [dihedral angle = 5.14 (8)°] and the furan unit makes dihedral angles of 70.27 (11) and 57.58 (8)° with the planes of the phenyl and the second phenanthrene group, respectively. In the crystal, neighbouring mol-ecules are connected via two inter-molecular hydrogen-bonding inter-actions (O-H⋯O and C-H⋯O) towards the carbonyl O atom with donor-acceptor distances of 2.824 (2) and 3.277 (3) Å, creating an inversion dimer. A non-classical C-H⋯Cl inter-action [3.564 (2) Å] and three C-H⋯π inter-actions, with C⋯π distances of 3.709 (3), 3.745 (2) and 3.628 (3) Å, connect the mol-ecules, forming a three-dimensional supra-molecular architecture in the solid state.

Crystal structure of 2-[(E)-4-benz-yloxy-2-hy-droxy-benzyl-idene]-N-cyclo-hexyl-hydrazinecarbo-thio-amide aceto-nitrile hemisolvate.

The asymmetric unit of the title compound, C21H25N3O2S·0.5C2H3N, contains two independent mol-ecules with almost similar structural properties along with a solvent mol-ecule of aceto-nitrile. The compound exists in the E conformation with respect to the azomethine C=N double bond. The hydrazinecarbo-thio-amide moieties in both independent mol-ecules are almost planar [maximum deviations of 0.013 (2) and 0.007 (2) Å]. The mol-ecular conformation is stabilized in each case by an intra-molecular N-H⋯N hydrogen bond. In the crystal, pairs of N-H⋯S hydrogen bonds link each of the independent mol-ecules into inversion dimers. The dimers are inter-connected by means of three C-H⋯π inter-actions.

Dichlorido{(2E)-2-[phen-yl(pyridin-2-yl)methyl-idene]hydrazinecarbo-thio-amide}cadmium(II) methanol monosolvate.

In the title compound, [CdCl2(C13H12N4S)]·CH3OH, the coord-ination geometry of the Cd(II) ion is slightly distorted square-pyramidal, as indicated by the τ index of 0.36 (8). The S atom, two N atoms from the pyridyl-azomethine moiety and one of the Cl atoms comprise the basal plane, while the other Cl atom occupies the apical position. The hydrazinecarbo-thio-amide moiety adopts an E conformation with respect to the azomethine bond. The solvate mol-ecule in the crystal lattice plays a major role in inter-connecting adjacent mol-ecules by means of O-H⋯Cl and N-H⋯O hydrogen-bonding inter-actions. A supra-molecular three-dimensional architecture is sustained in terms of further N-H⋯Cl and C-H⋯Cl hydrogen-bonding inter-actions.

The molecular response of vanadium complexes of nicotinoyl hydrazone in cervical cancers--a possible interference with HPV oncogenic markers.

AIMS: Hydrazones belonging to the class of NNO donor Schiff bases are reported to have extensive anti-viral activity and anti-neoplastic activity against certain cancers such as colon cancer, hepatocellular carcinoma and testicular cancer. Here we aim to study the possible effects of two novel nicotinoyl hydrazones on Human papillomavirus (HPV) infected cervical cancers. MAIN METHODS: The effect of vanadium complexes on the proliferation of SiHa and HeLa cells was analyzed using MTT assay. The apoptotic potentials of the complexes were assessed by their ability to induce DNA condensation as well as loss of mitochondrial membrane potential. Caspase activity assay and DNA content analysis were performed to understand the mechanism of apoptotic induction. RT-PCR analysis of cell cycle genes, GADD45, p53, p21 and HPV specific oncogenes, E6 and E7 were used to elucidate the molecular mechanism of the complexes. KEY FINDINGS: OVK 49 exhibits an increased apoptosis inducing potential when compared to OVK 89 in HPV16 positive SiHa cells compared to HPV18 positive HeLa. A down regulation for E6 and E7 mRNA transcripts along with the induction of p53 protein in SiHa cells were observed when treated with OVK 49 indicating that OVK 49 might have promising anti-cancer activity against HPV16 positive cervical cancers. SIGNIFICANCE: This is the first study demonstrating that vanadium complexes could induce a p53 dependent apoptotic mechanism in high risk HPV16-positive cervical cancers.

Bis{µ-N-[(E)-4-benz-yloxy-2-oxidobenzyl-idene]-4-nitro-benzene-carbo-hydrazidato}bis-[di-aqua-nickel(II)] di-methyl-formamide tetra-solvate.

The molecule of the title complex, [Ni2(C21H15N3O5)2(H2O)4]·4C3H7NO, is located on an inversion centre. This results in a dimeric Ni(II) complex, with the two Ni(II) atoms bridged by phenolate O atoms. The tridentate ligand is chelated to each Ni(II) atom via one N and two O atoms of the imino-late form of the hydrazide moiety, which has the same conformation as the free ligand. The coordination geometry around each Ni(II) ion is slightly distorted octa-hedral. A supra-molecular three-dimensional architecture is created by dominant inter-molecular O-H⋯N, O-H⋯O and C-H⋯O hydrogen-bonding inter-actions. These are augmented by two C-H⋯π inter-actions and a π-π inter-action with a centroid-centroid distance of 3.681 (2) Å.

(2E,7E)-2,7-Bis[(thio-phen-2-yl)methyl-idene]cyclo-hepta-none.

The whole molecule of the title compound, C17H16OS2, is generated by two-fold rotational symmetry. The carbonyl C and O atoms of the cycloheptanone ring lie on the twofold rotation axis which bisects the opposite -CH2-CH2- bond of the ring. The mol-ecule exists in an E,E conformation with respect to the C=C double bond. The cyclo-hepta-none ring exhibits a twisted chair conformation and its mean plane makes a dihedral angle of 50.12 (19)° with the planes of the thio-phene rings. The two S atoms are in an anti arrangement with respect the carbonyl O atom and the dihedral angle between the two thio-phene ring planes is 69.38 (7)°. In the molecule, there are two intramolecular C-H⋯S hydrogen bond, forming S(6) ring motifs. In the crystal, inversion dimers are generated via pairs of C-H⋯O hydrogen bonds. These dimers are inter-connected by another inter-action of the same kind with a neighbouring mol-ecule, forming a mol-ecular chain along the c-axis direction.

N'-[(E)-1-(2-Fluoro-phen-yl)ethyl-idene]pyridine-4-carbohydrazide.

The title compound, C14H12FN3O, adopts an E conformation with respect to the azomethine bond. The pyridyl and fluoro-benzene rings make dihedral angles of 38.58 (6) and 41.61 (5)° respectively with the central C(=O)N2CC unit, resulting in a non-planar mol-ecule. The inter-molecular inter-actions comprise two classical N-H⋯O and N-H⋯N hydrogen bonds and four non-classical C-H⋯O and C-H⋯F hydrogen bonds. These inter-actions are augmented by a weak π-π inter-action between the benzene and pyridyl rings of neighbouring mol-ecules, with a centroid-centroid distance of 3.9226 (10) Å. This leads to a three-dimensional supra-molecular assembly in the crystal system. The F atom is disordered over two sites in a 0.559 (3): 0.441 (3) ratio, through a 180° rotation of the fluoro-benzene ring.

N'-[(E)-(3-Fluoro-pyridin-2-yl)methyl-idene]pyridine-3-carbohydrazide dihydrate.

The organic molecule in the title dihydrate, C12H9FN4O·2H2O, exists in the E conformation with respect to the azo-methane C=N double bond. The mol-ecule is approximately planar, with a maximum deviation of 0.117 (1) Šfor the carbonyl O atom from the mean plane of the mol-ecule. Both pyridine rings are essentially coplanar with the central C(=O)N2C unit [dihedral angles = 1.99 (7) and 5.71 (8)°], exhibiting a significant difference in dihedral angles from its benzohydrazide analogue. The crystal packing features N-H⋯O, O-H⋯N and O-H⋯O hydrogen-bond inter-actions, which lead to the formation of a chain along the c-axis direction through one of the water mol-ecules present, and these chains are stacked one over the other by means of π-π inter-actions [with centroid-centroid distances of 3.7099 (10) and 3.6322 (10) Å] between the aromatic rings in neighbouring anti-parallel mol-ecules, building a three-dimensional supra-molecular network.

(E)-2-(4-Benz-yloxy-2-hy-droxy-benzyl-idene)-N-methyl-hydrazinecarbo-thio-amide.

The mol-ecule of the title compound, C16H17N3O2S, adopts an E conformation with respect to the azomethine C=N bond. The hydrazinecarbo-thio-amide fragment is close to planar, with a largest deviation from the least-squares plane of 0.079 (2) Šfor the hydrazide N atom. This fragment forms a dihedral angle of 9.43 (9)° with the central benzene ring. The benzene rings are inclined to one another by 67.55 (12)°. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond involving the azomethine N atom. In the crystal, mol-ecules are linked through weak N-H⋯S and N-H⋯O hydrogen bonds into double ribbons along [010]. The crystal packing also features C-H⋯π inter-actions.