Synthesis, characterization, DNA binding, cleavage activity, cytotoxicity and molecular docking of new nano water-soluble [M(5-CH2PPh3-3,4-salpyr)](ClO4)2 (M = Ni, Zn) complexes

Some new water soluble complexes [N, N'-bis{5-[(triphenyl phosphonium chloride)-methyl] salicylidine}-3,4-diaminopyridine] M(II), which are formulated as nano-[Zn(5-CH2PPh3-3,4-salpyr)](ClO4)(2) (1), [Zn(5CH(2)PPh(3)-3,4-salpyr)](ClO4)(2) (2), nano-[Ni(5-CH2PPh3-3,4-salpyr)](ClO4)(2) (3), [Ni(5-CH2PPh3-3,4-salpyr)] (ClO4)(2) (4), and [N, N'-bis{5-[(triphenyl phosphonium chloride)-methyl] salicylidine}-2,3-diaminopyridine] Ni(II) [Ni(5-CH2PPh3-2,3-salpyr)](ClO4)(2) (5) have been isolated and characterized by elemental analysis, FT-IR, H-1 NMR, C-13 NMR, P-31 NMR, and UV-vis spectroscopy. The morphology and size of the nano complexes were determined using FE-SEM and TEM. In vitro DNA binding studies were investigated by UV-vis absorption spectroscopy, viscosity measurements, CD spectroscopy, cyclic voltammetry, emission spectra and gel electrophoresis, which suggest that the metal complexes act as efficient DNA binders. The absorption spectroscopy of the compounds with DNA reveals that the DNA binding affinity (Kb) has this order: 3 > 4 > 5 > 1 > 2 > Ligand. The metal complexes show DNA binding stronger than the ligand, which is expected due to the nature of the metal. The nano complexes display DNA binding stronger than the other complexes which is related to the effect of size on binding affinity and the Ni(II) complexes reveal DNA binding stronger than the corresponding Zn(II) analogues, which is expected due to their z* effect and geometry. The prominent double strand DNA cleavage abilities of compound 3 are observed in the absence of H2O2 with efficiencies of more than 50% even at 70 mu M complex concentration. Surprisingly, Zn(II) complexes (compounds 1 & 2) exhibit a higher cytotoxicity (IC50: 7.3 & 10.9 mu M at 24 h; IC50: 4.6 & 8.7 mu M at 48 h) against human hepatoma (HepG2) and HeLa cell lines than the Ni(II) complexes (compounds 3, 4 & 5) and 5-fluorouracil as control in spite of their inability to cleave DNA. Finally, DNA binding interactions were performed by docking studies. Density functional theory (DFT) studies were performed using the GAUSSIAN 03 program. The DFT method with B3LYP functional, LANL2DZ basis set for metal centers and 6-311g* for other atoms was used. The synthesized compounds and DNA were simulated by molecular docking to explore more details of the ligands conformation and their orientations in the active site of the receptor.