DNA binding, DNA hydrolysis and phosphatase-like activity of new macrobicyclic dicopper(II) complexes

Abstract

A new class of macrobicyclic dicopper(II) complexes, [Cu2L1–2B](ClO4)4 (1–4) where L1–2 are polyaza macrobicyclic binucleating ligands and B is a N,N-donor heterocyclic base (viz. 2,2-bipyridyl (bipy) and 1,10-phenanthroline (phen)), have been prepared and characterized. The redox, catalytic, DNA binding and DNA cleavage properties were also studied. They exhibit a quasi-reversible cyclic voltammetric response near −0.5V versus Ag/AgCl in CH3CN–0.1M TBAP, assignable to the Cu2II/Cu2I redox couple. The initial rate values for the hydrolysis of 4-nitrophenylphosphate to 4-nitrophenolate by the dicopper(II) complexes 1–4 are 1.3×10−5, 0.9×10−5, 4.3×10−4 and 3.5×10−4Ms−1, respectively. Complexes 2 and 4 show a good binding propensity to calf thymus DNA, giving binding constant values in the range 1.02×105–8.32×105M−1. The binding site size and viscosity data suggest a DNA intercalative and/or groove binding nature of the complexes. The complexes display significant hydrolytic cleavage of supercoiled pBR322 DNA at pH 7.2 and 37°C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo Michaelis–Menton kinetic parameters kcat=5.23±0.3h−1 and KM=6.42×10−3M were obtained for complex 4.