The reaction of 2-hydroxybenzoylhydrazine (Hbh) separately with equimolar amounts of [VO(aa)] and [VO(ba)] in CHCl afforded the complexes [VO(HL)] (1) and [VO(HL)] (2) respectively in good to excellent yield ((HL) and (HL) represent respectively the dianionic form of 2-hydroxybenzoylhydrazones of acetylacetone (HL) and benzoylacetone (HL) (general abbreviation HL)). From X-ray structure analysis, the V-O-V angle was found to be ∼115° and 180° in 1 and 2 respectively. Upon one-electron reduction selectively at one V centre at an appropriate potential, each of 1 and 2 generated mixed-valence [(HL)VO-(μ-O)-OV(HL)] species 1A and 2A respectively, which showed valence delocalization at room temperature and localization at 77 K, and the V-O-V bond angles were calculated to be 177.5° and 180° respectively. The intercalative mode of binding of the two complexes 1 and 2 with CT DNA has been suggested by UV-visible spectroscopy (K = 7.31 × 10 M and 8.71 × 10 M respectively for 1 and 2), fluorescence spectroscopy (K = 6.85 × 10 M and 8.53 × 10 M respectively for 1 and 2) and circular dichroism spectroscopy. Such intercalative mode of binding of these two complexes with CT DNA and HPV DNA has also been confirmed by molecular docking study. Both complexes 1 and 2 exhibited promising anti-cancer activity against SiHa cervical cancer cells with IC values of 28 ± 0.5 μM and 25 ± 0.5 μM respectively for 24 h which is significantly better than that of widely used cisplatin (with IC value of 63.5 μM). Nuclear staining experiments reveal that these complexes kill the SiHa cells through apoptotic mode. It is interesting to note that these two complexes are non-toxic to normal T293 cell line. Complex 2 showed higher DNA binding ability with CT DNA and HPV DNA as well as better anti-cancer properties towards SiHa cervical cancer cells in comparison to complex 1, a fact which can be explained by considering the lower energy of LUMO (which favours electron transition from DNA to the metal complex) and also the higher surface area of complex 2 in comparison to complex 1 due to the presence of one extra electron-withdrawing phenyl group in the former.

No abstract

Substituents at 5-position in the acetophenone ring of the hydrazone ligands in a family of mixed-ligand oxidovanadium(v) complexes show marked influence on the electronic properties, DNA binding ability and nuclease activity.

Refluxing [VO(β-diketonate)], namely [VO(acetylacetonate)] and [VO(benzoylacetonate)], separately with an equivalent or excess amount of 2-aminobenzoylhydrazide (ah) in laboratory grade (LG) CHOH in aerobic conditions afforded non-oxidovanadium(iv) and oxidovanadium(v) complexes of the type [V(L)] (1), [VO(L)(OCH)] (3) and [V(L)] (2), and [VO(L)(OCH)] (4), respectively. (L) and (L) represent the dianionic forms of 2-aminobenzoylhydrazone of acetylacetone (HL) and benzoylacetone (HL), respectively, (general abbreviation, HL), which was formed by the in situ condensation of ah with the respective coordinated [β-diketonate] in medium-to-good yield. The yield of different resulting products was dependent upon the ratio of ah to [VO(β-diketonate)]. For example, the yield of 1 and 2 complexes increased significantly associated with a decrease in the amount of 3 and 4 with an increase in the molar ratio of ah. Upon replacing CHOH by a non-hydroxylic solvent, LG CHCl, the above reaction yielded only oxidovanadium(v) complexes of the type [VO(L)(OH)] (5), [VO(L)(OH)] (6) and [VO(L)] (7, 8) whereas, upon replacing CHCl by another non-hydroxylic solvent, namely LG CHCN, only the respective [VO(L)] (7, 8) complex was isolated in 72-78% yield. However, upon performing the above reactions in the absence of air using dry CHOH or dry CHCl, only the respective [V(L)] complex was obtained, suggesting that aerial oxygen was the oxidising agent and the type of pentavalent product formed was dependent upon the nature of solvent used. Complexes 3 and 4 were converted, respectively, to 7 and 8 on refluxing in LG CHClvia the respective unstable complex 5 and 6. The DFT calculated change in internal energy (ΔE) for the reactions 2[VO(L)(OCH)] + 2HO → 2[VO(L)(OH)] + 2CHOH and 2[VO(L)(OH)] → [VO(L)] + HO was, respectively, +3.61 and -7.42 kcal mol, suggesting that the [VO(L)(OH)] species was unstable and readily transformed to the stable [VO(L)] complex. Upon one-electron reduction at an appropriate potential, each of 7 and 8 generated mixed-valence [(L)VO-(μ-O)-OV(L)] species, which showed valence-delocalisation at room temperature and localisation at 77 K. Some of the complexes showed a wide range of toxicity in a dose-dependent manner against lung cancer cells comparable with that observed with cis-platin.