High nuclease activity of a copper(II)-bipyridyl complex containing cytosine pendants

Abstract

A new copper(II) complex bearing 2,2′-bipyridine (bpy) derivatives with cytosine nucleobases [Cu(L)Cl2] · 2H2O has been synthesized and characterized, where L = 5,5′-di[(4-amino-2-oxo-1(2H)-pyrimidinyl)methyl]-2,2′-bipyridine. Circular dichroism spectra reveal interactions between ligand and pBR322 DNA and showed that the local DNA structure was perturbed by the ligand. Cleavage of pBR322 DNA by the title complex was carried out in 20 mmol L−1 HEPES (pH 7.5) at 37°C. The calculated pseudo-Michaelis–Menten kinetic parameter (k cat) of the complex was 8.80 h−1. The cleavage efficiency was 17-fold higher than that of its simple analog [Cu(bpy)Cl2] (k cat = 0.50 h−1). Hydrolytic mechanisms involved in DNA cleavage were explored using radical scavengers and T4 ligase. Competitive experiments with special binding agents showed that the complex could preferentially bind to the minor groove of double-stranded DNA, suggesting specific DNA binding characteristics. High DNA cleavage reactivity and selectivity of the complex could be attributed to the synergic effects of the metal center and the cytosine pendants.