Two Cu(II) complexes containing 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and amino acids: Synthesis, crystal structures, DNA/HSA binding, molecular docking, and in vitro cytotoxicity studies

Abstract

Two new copper(II)-amino acid complexes, [Cu(PyTA)(l-Thr)(ClO4)]2·1.5H2O (1) and [Cu(PyTA)(l-Arg)(ClO4)(H2O)]·ClO4 (2) (PyTA=2,4-diamino-6-(2-pyridyl)-1,3,5-triazine, l-Thr=l-threonine, l-Arg=l-arginine), were successfully synthesized and characterized. The results determined by single crystal X-ray diffraction showed that the five-coordinated copper of 1 and the six-coordinated copper of 2 were located in the distorted square-pyramidal and distorted octahedral environments, respectively. Spectroscopic titrations, thermal denaturation experiments, viscosity measurements revealed that the complexes bound to DNA via a groove binding mode, with the DNA-binding constants of 6.126×104M−1 for 1 and 6.464×104M−1 for 2. Electrophoresis experiments revealed that the complexes cleaved pBR322 DNA by an oxidative pathway involving in the generation of superoxide free radical (O2−). Multi-spectroscopic analyses showed that the complexes bound to site I of human serum albumin (HSA) with moderate affinities. In particular, in vitro cytotoxicities of the complexes against Bel-7402 cell line showed promising anticancer effects (IC50=42.1±1.7μM for 1; IC50=36.3±0.9μM for 2). In addition, the binding mechanism and mode of the complexes with DNA/HSA were verified by molecular docking technique.