DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Abstract

AbstractThe reaction of 2‐chloro‐4,6‐bis(di‐2‐picolylamino)‐1,3,5‐triazine (bdpaTCl) with copper(II) perchlorate and copper(II) chloride afforded two dinuclear complexes [Cu2(μ‐bdpaTCl)(μ‐OH)2(H2O)0.5(ClO4)0.5](ClO4)1.5·(H2O)1.5 (1) and [Cu2(μ‐bdpaTCl)Cl4]·2CH3OH (2), respectively. These complexes were characterized by IR, UV/Vis, and EPR spectroscopy, single‐crystal X‐ray crystallography, and temperature dependence magnetic susceptibility measurements (2–300 K) as well as by electrochemical and molar conductivity measurements. In 1, each of the three N‐donor atoms of the binucleating bdpaTCl ligand coordinate to CuII ions, which are further bridged by two OH– anions in a distorted five‐coordinate geometry. In addition, each CuII ion forms a Cu–O semicoordinate bond with an aqua ligand or perchlorato anion. The Cu···Cu distance across the hydroxido bridges is 2.9698(11) Å. In 2, the bdpaTCl ligand acts as bis‐tridentate ligand connecting the two CuII ions, and the five‐coordinate geometry around each copper center is achieved by two terminal chloro ligands. Magnetic measurements revealed strong antiferromagnetic coupling in 1 (J = –311.2 cm–1) and very weak coupling in 2 (J = –2.4 cm–1). DNA cleavage by these two complexes has been investigated (pH = 7.0, 37 °C). Although the bridged dihydroxido complex 1 did not show any detectable cleavage for DNA, significant cleavage was observed with the tetrachloro complex 2. Under pseudo‐Michaelis–Menten kinetic conditions, the kinetic parameters kcat = 2.53 × 10–5 s–1 and KM = 1.44 × 10–4 M were determined for 2. The kcat value corresponds to a 2.5 × 106 fold rate enhancement over noncatalyzed DNA. Electrophoretic experiments conducted in the presence and absence of oxidative scavengers DMSO, KI, and NaN3, and radical promoter H2O2 provide evidence for the oxidative cleavage of DNA by hydroxy radicals and hydrogen peroxide species.