Copper(ii) complexes of 2-methyl-8-hydroxyquinoline and tri/diimine co-ligand: DFT calculations, DNA and BSA binding, DNA cleavage, cytotoxicity and induction of apoptosis†‡
Abstract
The mixed ligand copper(II) complexes [Cu(terpy)(mq)]ClO4 (1) and [Cu(phen)(mq)]ClO4 (2), in which terpy = 2,2′:6′,2′′-terpyridine, phen = 1,10-phenanthroline and H(mq) = 2-methyl-8-hydroxyquinoline, have been synthesized. The crystal structure of 1 discloses a distorted square-pyramidal geometry (τ = 0.16). The coordination geometry around Cu(II) in the density functional theory optimized structures of 1 and 2 has been assessed and found to show a distorted square pyramidal and square planar respectively. They exhibit a ligand field band and their frozen solution EPR spectra are axial (g‖ > g⊥ > 2.0) suggesting a square-based geometry around Cu(II) with a dx2−y2 ground state. The complexes interacted with calf thymus (CT) DNA and were found to be groove binding, as determined by various spectral and redox techniques. Interestingly, 2 cleaves supercoiled ϕX174 DNA without a reductant while 1 cleaves with the reductant. Furthermore, the quenching of the tryptophan emission of BSA in the presence of the complexes is static. The binding is mainly entropy-driven and hydrophobic forces played a major role. The DNA and protein binding affinity and the DNA cleavage activity is in the order 2 > 1, and the higher DNA and protein binding affinity and DNA cleavage activity of 2 illustrates the strong involvement of the 2-methyl group on the mq ring in the hydrophobic interaction with the DNA and protein. Furthermore, cytotoxicity studies of 1 and 2 on MCF7 and SiHa cell lines show that the IC50 values are lower than those of cisplatin and illustrate a lower cytotoxicity against the Jurkat T4 normal cell line. AO/EB and Hoechst 33258 staining assays reveal the higher induction of apoptosis for 1 and 2. The alkaline single-cell electrophoresis (comet assay) indicates that the complexes induce DNA fragmentation, which provides additional proof of the apoptosis.