Monomeric and Dimeric Oxidomolybdenum(V and VI) Complexes, Cytotoxicity, and DNA Interaction Studies: Molybdenum Assisted C═N Bond Cleavage of Salophen Ligands.

Four novel dimeric bis-µ-imido bridged metal-metal bonded oxidomolybdenum(V) complexes [MoV2O2L'21-4] (1-4) (where L'1-4 are rearranged ligands formed in situ from H2L1-4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido-bridged complexes (1-4) have been furnished from rearranged H3L'1-4 ligands, containing an aromatic diimine (o-phenylenediamine) "linker", where Mo assisted hydrolysis followed by -C═N bond cleavage of one of the arms of the ligand H2L1-4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL'1-4)(OEt)] (Id1-4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1-4) ultimately resulted in the formation of a bis-µ-imido bridge between the two molybdenum centers of [MoV2O2L'21-4] (1-4). The mechanism of formation of 1-4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic "linker" was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV-vis spectroscopy, NMR, ESI-MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1-5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M-1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines.

Mercury based drug in ancient India: The red sulfide of mercury in nanoscale.

Mercury is one of the elements which had attracted the attention of the chemists and physicians of ancient India and China. Among the various metal based drugs which utilize mercury, we became interested in the red sulfide of mercury which is known in ancient Indian literature as rasasindur (alias rasasindura, rasasindoor, rasasinduram, sindur, or sindoor) and is used extensively in various ailments and diseases. Following various physico-chemical characterizations it is concluded that rasasindur is chemically pure α-HgS with Hg:S ratio as 1:1. Analysis of rasasindur vide Transmission Electron Microscopy (TEM) showed that the particles are in nanoscale. Bio-chemical studies of rasasindur were also demonstrated. It interacts with Bovine Serum Albumin (BSA) with an association constant of (9.76 ± 0.56) × 103 M-1 and behaves as a protease inhibitor by inhibiting the proteolysis of BSA by trypsin. It also showed mild antioxidant properties.

A study of DNA/BSA interaction and catalytic potential of oxidovanadium(v) complexes with ONO donor ligands.

The study of DNA/BSA interaction and the catalytic potential of four mononuclear oxidoalkoxido vanadium(v) [VVO(L1-4)OEt] (1-4) and one dinuclear oxidoalkoxido mixed-ligand vanadium(v) [{VO(L2)OEt}2(Q)]{Q = 4,4'-bipyridine}(5) complexes, with tridentate binegative aroylazine ligands are reported [where H2L1 = anthranylhydrazone of 2-hydroxy-1-napthaldehyde, H2L2 = salicylhydrazone of 2-hydroxy-1-napthaldehyde, H2L3 = benzoylhydrazone of 2-hydroxy-1-acetonaphthone, H2L4 = anthranylhydrazone of 2-hydroxy-1-acetonaphthone]. All the complexes are characterized by elemental analysis as well as various spectroscopic techniques. Single crystal X-ray diffraction crystallography of 2 reveals that the metal centre is in distorted square pyramidal geometry with O4N coordination spheres, whereas 5 exhibits a distorted octahedral geometry around the metal center. In addition, all the complexes (1-5) show moderate DNA binding propensity which is investigated using UV-vis absorption titration, circular dichroism, thermal denaturation and fluorescence spectral studies. The experimental results show that the complexes effectively interact with CT-DNA through both minor and major groove binding modes, with binding constants ranging from 104-105 M-1. Among 1-5, complexes 3 and 4 show higher binding affinity towards CT-DNA than others and at the same time also exhibit negative ΔTm values of about ∼1.5 and 1.0 °C which resembles the properties shown by cisplatin. All complexes show moderate photo-induced cleavage of pUC19 supercoiled plasmid DNA with complex 3 showing the highest photo induced DNA cleavage activity of ∼48%. In coherence with the DNA interaction studies, 3 and 4 also exhibit good binding affinity towards BSA in the range of 1010-1011 M-1, which is also supported by their ability to quench the tryptophan fluorescence emission spectra of BSA. All the complexes show remarkable photo-induced BSA cleavage activity (>90%) at a complex concentration of 50 µM. The catalytic potential of 1-5 is also tested for the oxidative bromination of styrene, salicylaldehyde and oxidation of methyl phenyl sulphide. All the reactions show a high percentage of conversion (>90%) with a high turnover frequency (TOF). Particularly, in the oxidative bromination of styrene the percentage of conversion and TOF vary from 96-98% and 8000-19 600 (h-1) respectively, which signifies the potential of these oxidovanadium(v) complexes to stimulate research for the synthesis of a better catalyst.

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.

Evaluation of the cell cytotoxicity and DNA/BSA binding and cleavage activity of some dioxidovanadium(V) complexes containing aroylhydrazones.

Three dioxidovanadium(V) complexes [VO2L(1-3)] (1-3) [HL(1)=1-napthoyl hydrazone of 2-acetyl pyridine, HL(2)=2-furoyl hydrazone of 2-acetyl pyridine and H2L(3)=isonicotinoyl hydrazone of 2-hydroxy benzaldehyde] have been reported. All the complexes were characterized by various spectroscopy (IR, UV-visible and NMR) and the molecular structures of 1 and 2 were characterized by single crystal X-ray diffraction technique. Structural report established five-coordinate geometries, distorted toward square pyramidal for each of 1 and 2, based on a tridentate -O,N,N coordinating anion and two oxido-O atoms. The experimental results show that the complexes interact with calf-thymus DNA (CT-DNA) possibly by a groove binding mode, with binding constants of ~10(5)M(-1). All complexes show good photo-induced cleavage of pUC19 supercoiled plasmid DNA with complex 1 showing the highest photo-induced DNA cleavage activity of ~68%. 1-3 also exhibit moderate binding affinity in the range of 10(3)-10(4)M(-1) towards bovine serum albumin (BSA), while all the complexes show good photo-induced BSA cleavage activity. Moreover the antiproliferative activity of all these complexes was studied, which reveal all compounds are significantly cytotoxic towards the HeLa cell line.

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.

A S52P mutation in the 'α-crystallin domain' of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function.

Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major immunodominant antigen of M. leprae pathogen. Previously, we have reported the existence of two M. leprae HSP18 variants in various leprotic patients. One of the variants has serine at position 52, whereas the other one has proline at the same position. We have also reported that HSP18 having proline at position 52 (HSP18P(52)) is a nonameric protein and exhibits chaperone function. However, the structural and functional characterization of wild-type HSP18 having serine at position 52 (HSP18S(52)) is yet to be explored. Furthermore, the implications of the S52P mutation on the structure and chaperone function of HSP18 are not well understood. Therefore, we cloned and purified these two HSP18 variants. We found that HSP18S(52) is also a molecular chaperone and an oligomeric protein. Intrinsic tryptophan fluorescence and far-UV CD measurements revealed that the S52P mutation altered the tertiary and secondary structure of HSP18. This point mutation also reduced the oligomeric assembly and decreased the surface hydrophobicity of HSP18, as revealed by HPLC and 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid binding studies, respectively. Mutant protein was less stable against thermal and chemical denaturation and was more susceptible towards tryptic cleavage than wild-type HSP18. HSP18P(52) had lower chaperone function and was less effective in protecting thermal killing of Escherichia coli than HSP18S(52). Taken together, our data suggest that serine 52 is important for the larger oligomerization and chaperone function of HSP18. Because both variants differ in stability and function, they may have different roles in the survival of M. leprae in infected hosts.