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The hydroxy analog of vitamin K3 (2-methylnaphthalene-1,4-dione) is known as phthiocol (2-hydroxy-3-methylnaphthalene-1,4-dione; pht). Both vitamin K3 and phthiocol possess anticancer and antihemorrhagic properties. Phthiocol is a noninnocent ligand and provides monodentate, bidentate, or tridentate coordination sites to metal ions. A series of transition metal complexes (Mn(II); 1 and 1A, Co(II); 2 and 2A, Ni(II); 3 and 3A, Cu(II); 4 and 4A, and Zn(II); 5 and 5A) are synthesized at 0 °C using sodium metal (1 to 5) and at 26 °C (1A to 5A). The chemical composition of the complexes obtained is of the type [M(phthiocolate)

Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. FT1 crystallizes in the triclinic system while FT2 in the orthorhombic. The DNA cleavage activity of Cu(II) complexes was studied using plasmid pBR322 DNA by gel electrophoresis. All compounds cleave DNA on photoirradiation by oxidative mechanism. Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. Both the Cu(II) complexes of indole thiocarbohydrazones are shown to cleave plasmid pBR322 DNA by oxidative mechanism.

Design and development of drugs in multi-drug resistant (MDR) infections have been of growing interest. We report the syntheses, and antibacterial and antifungal activities of imidazole-based 1,4-naphthoquinones (I-1 to I-4; 1-alkyl-2-methyl-1H-naphtho[2,3-d]imidazole-4,9-dione (alkyl = methyl to butyl)) and their precursors (B-3; N-(3-chloro-1,-dioxo-1,4-dihydronaphthalen-2-yl)acetamide) and A-1 to A-4; N-(3-(alkylamino)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)acetamide (alkyl = methyl to butyl). Crystal structures of B-3, A-1 to A-3 and I-2 to I-4 were obtained through single crystal X-ray diffraction experiments. Electronic structure and charge distribution have further been characterized with the use of Density Functional Theory. Seven of these derivatives display a broad spectrum of antibacterial activity against few selected bacterial strains (Gram-positive and Gram-negative). As demonstrated MIC values with B-2 and B-3 against bacterial isolates were 8–64 μg ml−1 and those against pathogenic yeast, C. albicans, were observed in the range of 128–256 μg ml−1. MIC data of these derivatives suggest them to be promising against pathogens.

Two new one-dimensional (1D) coordination polymers (CPs), namely catena-poly[[[aquacadmium(II)]-bis(μ-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione)] bis(perchlorate) dihydrate], {[Cd(C14H10N6O2)2(H2O)](ClO4)2·2H2O} n or {[Cd(BPG)2(H2O)](ClO4)2·2H2O} n , 1, and catena-poly[[lead(II)-bis(μ-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione)] bis(perchlorate) dihydrate], {[Pb(C14H10N6O2)2](ClO4)2·2H2O} n or {[Pb(BPG)2](ClO4)2·2H2O} n , 2, have been synthesized using bipyridine–glycoluril (BPG; systematic name: 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione), a urea-fused tecton, in a mixed-solvent system. The CdII ion in 1 is heptacoordinated and the PbII ion in 2 is hexacoordinated, with the CdII ion adopting a pentagonal bipyramidal geometry and the PbII ion adopting a distorted octahedral geometry. Both CPs form infinite linear chain structures which are hydrogen bonded to each other leading to the formation of three-dimensional supramolecular network structures. Topological analysis of CPs 1 and 2 reveals that the structures exhibit 1D chain-like arrangements in an AB–AB sequence and shows platonic uniform 2-connected uninodal topologies. Furthermore, a comparative analysis of a series of structures based on the BPG ligand indicates that the size of the metal ion and the types of counter-ions used have a great influence on the resulting frameworks and properties.

Homologated (N)-n-alkylammonium salts of 2-bromo-3-oxido-1,4-naphthoquinone (BS-1 to BS-8) have been synthesized and characterized from the single crystal X-ray diffraction experiments combined with density functional theory. The crystal structures revealed diverse noncovalent interactions such as hydrogen bonding, π∙∙∙π, Br∙∙∙π, and others. The measured antifungal activities of the BS-1 to BS-6 against fungal strains Saccharomyces cerevisiae and Candida albicans suggest them to be effective compared to standard drug amphotericin B. Antibacterial activity of BS-1 to BS-6 has been evaluated against Gram-positive and Gram-negative bacteria.

Synthesis and characterization of five amphiphilic ruthenium(II) complexes of the type [Ru(Cn)3].(PF6)2 (Cn = 4,4′-dialkyl-2,2′-bipyridine, n = 5(4,4′-dipentyl), 6(4,4′-dihexyl), 7(4,4′-diheptyl), 8(4,4′-dioctyl), 9(4,4′-dinonyl)) have been investigated. Single crystal X-ray structures of 4,4′-dipentyl-2,2′-bipyridine (C5), 4,4′-dioctyl-2,2′-bipyridine (C8) ligands and [Ru(C5)3](PF6)2 complex are elucidated. Structural inferences are corroborated through the density functional theory. Molecular aggregations in these systems in aqueous and non-aqueous media have further been analyzed from FESEM experiments.

1H as well as 13C chemical shifts of 32 compounds of C (3) substituted 2-(n-alkylamino)-3R-naphthalene-1,4-dione (where n-alkyl: methyl, to octyl, R = H, Cl, Br, and CH3) are investigated through 1H, 13C, DEPT, gDQCOSY, and gHSQCAD NMR experiments and M06-2X/6-311++G (d,p) density functional theory are discussed. Single crystal X-ray structure of Br-3, as well as 18 different derivatives of naphthalene-1,4-diones, are revealed for its inter and intra-molecular hydrogen bonding interactions., Naphthoquinone; Aminonaphthoquinone; Chemical shift; 2D NMR.

Reactions of 2,3-dichloro-1,4-naphthoquinone with o/m and p-aminophenols are studied. It was shown that reaction with 2-aminophenol results in 6-chloro-12a-methoxy-7H-benzo[c]phenozaxine-5(12aH)-one (1a) as the major product along with (6-chloro-12a-hydroxy-7H-benzo[c]phenoxazine-5(12aH)-one) (1b) in minor proportions. A major 6-chloro-12a-methoxy-9-methyl-7H-benzo[c]phenoxazin-5(12aH)-one (2a) was isolated from the 4-methyl-2-aminophenol whereas reactions with 3-aminophenol and 4-aminophenol yield products 2-(3-hydroxyphenylamino)-3-chloro-1,4-naphthoquinone (3) and 2-(4-hydroxyphenylamino)-3-chloro-1,4-naphthoquinone (4). The hydroxy phenoxazine (1b) was obtained as the minor product which is evident from the single crystal X-ray diffraction studies. Pharmacological potential of these compounds have been evaluated against pathogenic Gram positive and Gram negative bacteria. These derivatives demonstrated broad spectrum of biological activity against all bacterial isolates with the MIC bring in the range of 4–512 μg/ml. The relatively high MICs were observed compared to the reference antibiotics used. Except 1b rest of the other compounds exhibit considerably lower MICs (32–512 μg/ml), against the two Pseudomonas spp. and relatively high resistance towards reference antibiotics (with the MIC being >1024 μg/ml). It has been shown that that synergistic action of phenoxazine derivatives in mixing with conventional antibiotics can be explored for treatment of pathogens.

Benzo[ a ]phenoxazines are the planar polycyclic fluorescent compounds, find a variety of applications in biological sciences and are of growing interest. In the present work we synthesized heterocyclic aromatic fluorescent benzo[ a ]phenoxazines namely, 6-methyl-9-nitro-5H-benzo[ a ]phenoxazin-5-one ( 1 ) and 6-methyl-10-nitro-5H-benzo[ a ]phenoxazin-5-one ( 2 ) which are characterized in terms of the 1 H and 13 C chemical shifts from 2D gHSQCAD NMR experiments. Single crystal X-ray experiments revealed both 1 and 2 possess the C H⋯O interactions. Moreover the π∙∙∙π stacking interactions between planar polycycles have been noticed only in 1 . The structural and vibrational spectral inferences obtained from experiments are corroborated through the ωB97xD based density functional theory.

Single crystal X-ray structures and vibrational spectra of (N)-n-alkylammonium 2-chloro-3-oxido-1,4-naphthoquinone salts (alkyl = methyl to octyl, CS-1 to CS-8) possessing X-H⋯Y (X = N, C and Y O, Cl) hydrogen bonding and diverse noncovalent interactions have been characterized. Except for the CS-2 and CS-7 rest of the compounds facilitate π⋯π and Cl⋯π interactions. The compound CS-3 showed the presence of Cl⋯O interactions. Electronic structure and spectral characteristics of obtained are in consonance with the density functional theory. These complexes showed remarkable antiproliferative and antifungal activities.

Synthesis of iminosugars 1, 2, 3a, and 4a and N-alkyl (ethyl, butyl, hexyl, octyl, decyl, and dodecyl) derivatives 3b–g and 4b–g spiro-linked with morpholine-fused 1,2,3-triazole is described. Conformation of the piperidine ring in each spiro-iminosugar was evaluated by 1H NMR spectroscopy, and conformational change in N-alkylated compounds 4b–g with respect to parent spiro-iminosugar 4a is supported by density functional theory calculations. Out of 16 new spiro-iminosugars, the spiro-iminosugars 3a (IC50 = 0.075 μM) and 4a (IC50 = 0.036 μM) were found to be more potent inhibitors of α-glucosidase than the marketed drug miglitol (IC50 = 0.100 μM). In addition, 3a (minimum inhibition concentration (MIC) = 0.85 μM) and 4a (MIC = 0.025 μM) showed more potent antifungal activity against Candida albicans than antifungal drug amphotericin b (MIC = 1.25 μM). In few cases, the N-alkyl derivatives showed increase of α-glucosidase inhibition and enhancement of antifungal activity compare to the respective parent iminosugar. The biological activities were further substantiated by molecular docking studies.

Two new one-dimensional (1D) coordination polymers (CPs), namely catena-poly[[[aquacadmium(II)]-bis(μ-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione)] bis(perchlorate) dihydrate], {[Cd(C

The synthesis and characterization of 2-((pyridine-2-yl)methylamino)naphthalene-1,4-dione (H-1), 2-((thiophen-2-yl)methylamino)naphthalene-1,4-dione (H-2) and 2-((pyridine/thiophen-2-yl)ethylamino)naphthalene-1,4-dione (H-3 and H-4) have been carried out. Molecular recognition abilities of these ligands toward transition metal ions in methanol, methanol–water, methanol–triethylamine or methanol–water–triethylamine mixtures, stoichiometries and association constants of H-1 and H-3 have been determined. It has been shown that H-1 and H-3 coordinate to metal ions via two nitrogen atoms and oxygen and exhibit remarkable selectivity towards Cu2+ ions in methanol or methanol–water mixtures, the complexation being accompanied by a color change from orange to intense blue. LOD (Limit of Detection) of Cu2+ with H-1, H-3 are 1.48 × 10−8 mol L−1 and 1.59 × 10−8 mol L−1 respectively. The vibrational spectra, 1H NMR chemical shifts and optical properties of H-1 to H-4 derived from density functional theory are also presented.

Molecular interactions underlying polymorphs of chlorine containing 1,4-naphthoquinone derivatives have been investigated by employing single crystal X-ray, 1H NMR, FTIR and electronic spectra experiments combined with density functional theory. Two polymorphs of 2,3-dichloro-1,4-naphthoquinone possessing (i) triclinic space group P-1(A1 and A3), and (ii) orthorhombic with Pb21a (A2) space group were obtained. The polymorph A3 has two molecules in its asymmetric unit which facilitate C H⋯O interactions engendeing polymeric planar sheets. The two polymorphs of 2-amino-3-chloro-1,4-naphthoquinone reveal monoclinic forms with Pc (B1) and C2/C (B2) space groups. A tetramer of B2 molecule possess N H⋯O interactions. The polymorphs of 2-chloro-3-hydroxy-1,4-naphthoquinone crystallizes in monoclinic space groups Pc (C1) and Pn (C2). Polymeric chain of C2 molecules results via O H⋯O interactions and the chains further are connected through C H⋯Cl and π-π stacking interactions those arise from benzenoid and quinonoid centroid. Moreover A3 facilitates the dimer via the halogen bonding interactions. Furthermore hydrogen bonding renders stability to the dimer C2. On the other hand compound B2 does not favor dimer formation. These inferences based on experimental observations are rationalized through the use of the dispersion corrected M06-2x functional based density functional theory. Further time dependent density functional theory has been used to assign the electronic transitions in UV–visible spectra of A3, B2 and C2.

Understanding the process of prenucleation clustering at supersaturating stage is of significant importance to envisage the polymorphism in crystalline materials. Preferential formation of a thermodynamically stable crystal form suggests energetically favored patterns of interactions which control molecular aggregation during nucleation. Introduction of additives during crystallization is sometimes used as a suitable strategy to obtain metastable polymorphs in cases where it is not easy to capture the same by conventional crystallization methods. Comparative analysis of energy relationships and intermolecular interactions between thermodynamically stable and metastable crystal forms provides valuable clues about the nature of growth synthons at prenucleation clustering and preferential crystallization of the thermodynamic form. Conformationally flexible sulfonamide/sulfoester derivatives constituting electron rich and electron-deficient aromatic rings were synthesized to study the interplay between π-stac...

Procainamide derivatives have been synthesized to investigate the role of side chains in modulating the DNA methylation level in cancer cells and gain insight into its mechanism of action. The synthesized derivatives comprised of flexible (dimethyl), constrained (pyrrolidine, piperidine, morpholine) and planar aromatic (pyridine, phenyl) side chain motifs. The affinity of procainamide and its derivatives towards the deoxyguanosine (dG) base in neutral form has been assessed by performing Differential Pulse Voltammetry (DPV) under physiological conditions. Further, molecular docking with hemimethylated CpG rich DNA acquired from an active mDNMT-1-DNA (PDB ID-4DA4) crystal structure, reveals their preferential non-covalent interaction with dG nucleobase in the intercalation cavity of the minor groove. Differential affinity of the derivatives to dG base in neutral and bound forms (DNA) is correlated with their DNA methylation modulating properties at sub-lethal concentrations. Among all the derivatives, a compound with an aromatic phenyl side chain (1) has shown a highest binding affinity for dG nucleobase in neutral form as well as for partially denatured CpG rich DNA which is attributed to the formation of π⋯π stacking interaction in addition to N–H⋯O hydrogen bonding with the pyrimidine ring of dG base. It also shows the highest cytotoxicity and global hypomethylation at a sub-lethal level in the MCF-7 cancer cell line compared to other derivatives and procainamide. A docking study has also illustrated the plausible structural basis of DNA methylation modulating a property of procainamide. Strong association of procainamide with dG bases of partially denatured CpG rich DNA via H-bonding and other non-covalent interactions may alter the active topology of DNA required by the DNA-binding regulatory proteins (e.g. DNMT-1) which is validated by a DNMT-1 inhibition assay. This systematic investigation leads to a new potent alternative to procainamide being found and gives a plausible insight into the DNA hypomethylating effect of procainamide.

This communication describes the utility of a conformationally restricted aromatic β-amino acid (2-aminobenzenesulfonic acid, (S)Ant) inducing various folding interactions in short peptides. Sandwiching (S)Ant between diverse amino acid residues was shown to form robust folded architectures featuring a variety of H-bonded networks, suggesting its utility in inducing peptide folding.

New unsymmetrical vicinal diamine ligands with systematic variation in the regio and stereo positions in the amine and sulphonamide groups were synthesized from cheap starting material such as norephedrine. Catalytic Asymmetric Transfer Hydrogenation (ATH) of aromatic alkyl ketones has been investigated using transition metal complexes and new derivatives of monotosylated unsymmetrical vicinal diamine ligands using sodium formate as the hydrogen source, in water and methanol. Chiral secondary alcohols were obtained with excellent enantioselectivity (>95% ee) and conversion of ketones (>95%) with [Rh(Cp*)Cl2]2 and ligand 4 as a catalyst. Enantioselectivity was found to be slightly higher with the use of methanol as a solvent for ATH of ketones with sodium formate as the hydrogen source compared to water as a solvent and was found to be consistent with all the ketones investigated. The reaction mixture is homogeneous in methanol unlike in water, where substrate and product are insoluble in water and form separate phase, sodium formate being soluble in water. The activity and enantioselectivity obtained for ATH of ketones using [Rh(Cp*)Cl2]2 and unsymmetrical vicinal diamine ligand as catalyst was comparable with the C2 symmetric benchmark ligands like TsDPEN ((1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenylethylene-diamine), and TsCYDN ((1R,2R)-N-(p-tolylsulfonyl)-1,2-cyclohexyl,diamine) under similar reaction conditions. To the best of our knowledge, this is first example of the ATH of ketones with good activity and high enantioselectivity with [Rh(Cp*)Cl2]2 and unsymmetrical vicinal diamine ligands as catalyst systems.

Bichelated neutral palladacycles (1-3), [Pd(L)Cl] were synthesized from reaction of the new potential tridentate (C,N,S) ligands, 2-thiobenzylazobenzene (L1), 4/-methyl-2-thiobenzylazobenzene (L2) and 4/-chloro-2-thiobenzylazobenzene (L3) with sodium tetrachloropalladate(II), Na2[PdCl4] in ethanol. The compounds were characterized by elemental analysis, FT-IR, 1H NMR, UV-Visible and thermogravimetric analysis. The crystal structures of L2 and 1-3 were determined by single-crystal X-ray diffraction. In 1-3, the geometry around palladium remains almost square planar, coordinated to carbon, nitrogen and sulfur of the ligand forming a bichelated cyclopalladate complex. The C−H…Cl type intermolecular hydrogen bonds, weak π…π, C-H…π and van der Waals interactions are believed to be the stabilizing forces for the crystal packing of these palladacycles.