Hydrolytic Cleavage of DNA by Ternary Amino Acid Schiff Base Copper(II) Complexes Having Planar Heterocyclic Ligands

Abstract

The ternary copper(II) complexes [Cu(salgly)L] (L = phen, 1; dpq, 2), [Cu(salala)L] (L = phen, 3; dpq, 4) and [Cu(salphe)L] (L = phen, 5; dpq, 6), where salgly, salala and salphe are tridentate Schiff-base ligands derived from the condensation of salicylaldehyde with glycine, L-alanine and L-phenylalanine, respectively, are prepared and their nuclease activity studied (phen, 1,10-phenanthroline; dpq, dipyridoquinoxaline). The crystal structure of 3 displays a distorted square-pyramidal (4+1) coordination geometry in which the ONO-donor Schiff base is bonded to the metal atom in the basal plane. The chelating phen ligand displays an axial-equatorial mode of bonding. The complexes exhibit a d-d band near 670 nm and a charge transfer band near 370 nm in methanol. The one-electron paramagnetic complexes display axial EPR spectra in DMF glass at 77 K, indicating a {d_x²-y²}¹ ground state. The complexes are redox-active and exhibit a quasi-reversible Cu^II/Cu^I couple in DMF at approximately -0.6 V vs. SCE. They show catalytic activity in the oxidation of ascorbic acid by molecular oxygen. The ability of the complexes to bind calf thymus (CT) DNA follows the order: 2 ≈ 4 ≈ 6 > 1 ≈ 3 ≈ 5. Complexes 1-6 show oxidative DNA cleavage activity in the presence of mercaptopropionic acid as a reducing agent. All the complexes show hydrolytic cleavage activity in the absence of light or any reducing agent. The oxidative and hydrolytic DNA cleavage efficiencies follow the order: 2 ≈ 4 ≈ 6 > 1 ≈ 3 ≈ 5. The dpq complexes, which have a greater DNA binding ability, display enhanced nuclease activity than their phen analogues. The hydrolytic DNA cleavage rate of 1.8 h^-1, observed for 2, is significantly high relative to most of the known copper-based synthetic hydrolases. Mechanistic pathways involved in the nuclease activity of the complexes are discussed.