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

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 x 2− y 2}1 ground state. The complexes are redox‐active and exhibit a quasi‐reversible CuII/CuI 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)