Synthesis, structure, DNA binding and oxidative cleavage activity of ternary ( l-leucine/isoleucine) copper(II) complexes of heterocyclic bases

Abstract

Six ternary α-amino acid copper(II) complexes of the general formula [Cu(AA)(B)(H 2O)](X) ( 1– 6), where AA is l-leu = l-leucine ( 1– 3) or l-ile = l-isoleucine ( 4– 6), B is a N, N-donor heterocyclic base, viz. 2,2′-bipyridine (bpy, 1, 4), 1,10-phenanthroline (phen, 2, 5) and dipyrido[3,2:2′,3′- f]quinoxaline (dpq, 3, 6) and X = ClO 4 - / NO 3 - have been synthesized, characterized, and their DNA binding and cleavage activity studied. The bpy and dpq complexes of l-ile ( 4, 6) have been structurally characterized by X-ray crystallography. The complexes show a distorted square-pyramidal (4 + 1) CuN 3O 2 coordination geometry. The one-electron paramagnetic complexes display a d–d band near 600 nm in water and show a cyclic voltammetric response due to a Cu(II)/Cu(I) couple near −0.1 V (vs. SCE) in DMF-0.1 M TBAP. All complexes are 1:1 electrolytes. Binding interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by absorption, emission, viscosity and DNA melting studies. The phen and dpq complexes are avid binders to the calf thymus DNA, giving an order: ( 3, 6) (dpq) > ( 2, 5) (phen) ≫ ( 1, 4) (bpy). The bpy complexes do not show any apparent binding to the DNA and hence show poor DNA cleavage activity. The phen and dpq complexes ( 2, 3, 5, 6) show efficient oxidative cleavage of pUC19 supercoiled DNA (SC-DNA) in the presence of the reducing agent 3-mercaptopropionic acid (MPA) involving hydroxyl radical ( OH) species, as evidenced from the control data showing inhibition of DNA cleavage in the presence of OH radical quenchers, viz. DMSO, mannitol, KI and catalase.