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

Six ternary a-amino acid copper(II) complexes of the general formula [Cu(AA)(B)(H2O)](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 = ClO4-/NO3 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) CuN3O2 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 TRAP. 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)-O-center dot) species, as evidenced from the control data showing inhibition of DNA cleavage in the presence of (OH)-O-center dot radical quenchers, viz. DMSO, mannitol, KI and catalase. (C) 2008 Elsevier Ltd. All rights reserved.