Exploring the effect of substituent in the hydrazone ligand of a family of μ-oxidodivanadium(v) hydrazone complexes on structure, DNA binding and anticancer activity

Abstract

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.

Controlling Nuclearity and Stereochemistry in Vanadyl(V) and Mixed Valent VIV/VV Complexes of Oxido‐Pincer Pyridine‐2,6‐dimethanol Ligands

“…E.g. V–O–V angles of reported complexes range from 107 to 180°,, , in line with our DFT‐optimized structures having several and/or broad minimum V–O–V angles.…”

“…The EPR parameters for the pydim and pydip derivative are similar to those of related mononuclear O=V IV complexes, , , and comparable dinuclear compounds with class I valence‐isolated [OV IV (μ‐O)V V O] units , , , , . Similar valence delocalized (class II or III) behavior as found for [V 2 O 3 (pyphen) 2 ] · – has been previously reported for the radical anionic complexes [(L)OV IV (µ‐O)V V O(LO] · – with tridentate ONO 2– ligands based on hydroxy phenoxy hydrazides,, , , salenes, carboxy‐salicylaldiminates, or azophenolates,, and also the [OV IV (μ‐O oxido )(μ‐O phen )V V O] · 2+ complexes containing pentadentate (N′NONN′) 3– 2,6‐bis(phenoxymethyl‐ N , N ‐dimethylaminomethyl)aminomethyl)‐phenolates,, or complexes [(L)OV IV (µ‐O)V V O(LO] · 3+ complexes containing neutral N′NN′ ligands of the 2,6‐bis[benzimidazol‐2′‐yl]pyridine or ‐amine type, tris(2‐pyridylmethyl)amine, or 1,4,7‐triazacyclononane derivatives …”

“…This has been nicely worked out on the mixed‐valence complexes [(HL)OV IV (μ‐O)V V O(HL)] · – with ONO 2– = hydroxybenzoylhydrazones of acetylacetone (HL 1 ) and benzoylacetone (HL 2 ) respectively, which showed valence delocalization at room temperature and localization at 77 K in glassy frozen solution. DFT calculations of the parent [OV V (μ‐O)V V O] complexes in solution gave similar structural parameters as found from single crystal XRD but the bond angles for the singly reduced [OV IV (μ‐O)V V O] · – radicals were calculated to 177.5 and 180° respectively, thus markedly different from the parent state for the complex based on acetylacetone (HL 1 ) and identical for the benzoylacetone (HL 2 ) derivative …”

“…The arrangement around the bridging O2 atom with V–O2–V angles of 117.1(3)° for the pydip complex and 129.5(6)° for the pyphen derivative revealing a syn‐angular configuration . Essential bond lengths show comparable values to other syn‐angular configured oxido‐bridged complexes with similar ligand systems (details in Tables S1 and S2, Supporting Information) …”

“…The overlap depends on the arrangement of the V–O–V moiety. Perfect overlap and class III delocalized systems are expected for a linear arrangement (V–O–V) and a torsion angle (O=V ··· V=O) of 180° , . Bending in the xy and yz planes also allows the possibilities of spin‐delocalization (class III and class II) but any torsion would hamper delocalization and lead to localized spins.…”