Synthesis of water soluble copper(II) complexes: crystal structures, DNA binding, oxidative DNA cleavage, and in vitro anticancer studies

Abstract

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H2O (1) and [Cu(Thr)(Phen)H2O]Cl·2H2O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (Kb) of (1) and (2) were 0.5 and 4.4 × 105 M−1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H2O2. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.