Three water-soluble acylhydrazone tetranuclear transition metal complexes: Crystal structures, DNA/BSA interactions and cytotoxicity studies.

2-acetylpyridine-4-chloropyridine-2‑carbonyl hydrazone (CHClNO, HL) and its three water-soluble tetranuclear complexes [Cu(NO)(L)]·(NO) (1), [Co(NO)(HO)(CHOH)(L)]·(NO) (2) and [Zn(NO)(HO)(CHOH)(L)]·(NO) (3) were synthesized and characterized showing that 1-3 were all tetranuclear complexes. The interactions of HL, 1-3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were explored using ultraviolet-visible (UV-Vis) titration, fluorescence spectroscopy, microcalorimetry and molecular docking techniques. The UV-Vis spectroscopy measurements showed that complexes 1-3 could strongly bind to CT-DNA by the intercalation mode, while HL interacted with CT-DNA through groove binding. From the fluorescence spectroscopy results, the interaction between HL, 1-3 and BSA was a static quenching procedure, in which complexes 1-3 had two binding sites near Trp residues of BSA while HL only had one. The microcalorimetric studies revealed that the interactions of HL and 1-3 to CT-DNA/BSA were all endothermic and the duration of each interaction was all less than 30 min. The in silico molecular docking illustrated intermolecular interactions of 1-3 binding with DNA/BSA included hydrogen bond, halogen bond, hydrophobic and electrostatic interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that complex 1 possessed better cytotoxicity against HeLa, A549, MCF7 and HCT-116 than cisplatin and could be used as an alternative anticancer drug.