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

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 -0.5 V versus Ag/AgCl in CH3CN-0.1 M TBAP, assignable to the Cu-2(II)/Cu-2(I) 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 x 10(-5), 0.9 x 10(-5), 4.3 x 10(-4) and 3.5 x 10(-4) M s(-1), respectively. Complexes 2 and 4 show a good binding propensity to calf thymus DNA, giving binding constant values in the range 1.02 x 10(5)-8.32 x 10(5) M-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 degrees 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 k(cat) = 5.23 +/- 0.3 h(-1) and K-M = 6.42 x 10(-3) M were obtained for complex 4. (C) 2011 Elsevier Ltd. All rights reserved.