New ternary copper(II) complexes of l-alanine and heterocyclic bases: DNA binding and oxidative DNA cleavage activity

Abstract

Four new ternary copper(II) complexes of α-amino acid having polypyridyl bases of general formulation [Cu( l-ala)(B)(H 2O)](X) ( 1–4), where l-ala is l-alanine, B is an N,N-donor heterocyclic base, viz. 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2) and 5,6-phenanthroline dione (dione, 3), dipyrido[3,2:2′,3′-f]quinoxaline (dpq, 4), and X = ClO 4 - / NO 3 - are synthesized, characterized by various spectroscopic and X-ray crystallographic methods. The complexes show a distorted square-pyramidal (4 + 1) CuN 3O 2 coordination geometry. The one-electron paramagnetic complexes ( 1– 4) display a low energy d–d band near 600 nm in aqueous medium and show a quasi-reversible cyclic voltammetric response due to one-electron Cu(II)/Cu(I) reduction near −100 mV (versus SCE) in DMF–0.1 M TBAP. Binding interactions of the complexes with calf thymus DNA (CT-DNA) were investigated by UV–Vis absorption titration, ethidium bromide displacement assay, viscometric titration experiment and DNA melting studies. All the complexes barring the complexes 1 and 3 are avid binder to the CT-DNA in the DNA minor groove giving an order: 4 > 2 ⋙ 1, 3. The complexes 2 and 4 show appreciable chemical nuclease activity in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent. Hydroxyl radical was investigated to be the DNA cleavage active species. Control experiments in the presence of distamycin-A show primarily minor groove-binding propensity for the complexes 2 and 4 to the DNA.