DNA binding, DNA hydrolase and phosphatase like activity of new polyaza macrobicyclic binuclear copper(II), nickel(II) and zinc(II) complexes

A new class of mono, polyaza macrobicyclic binuclear copper(II), nickel(II) and zinc(II) complexes 1–6 are synthesized and characterized. The redox, phosphate hydrolysis, DNA binding and cleavage properties of complexes 1–6 are studied. The mononuclear Cu(II)-complex 1 is structurally characterized by single-crystal X-ray diffraction study. They exhibit a quasi-reversible cyclic voltammetric response near −0.65 V versus Ag/AgCl in CH3CN-0.1 M TBAP assignable to the M2II/M2I redox couple. The initial rate values for the hydrolysis of 4-nitrophenylphosphate to 4-nitrophenolate by the complexes 1–6 are in the range from 1.82 × 10−6 to 1.25 × 10−4 s−1. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.1 to 9.5 × 105 M−1. The binding site size and viscosity data suggest the DNA groove binding of the complexes. The complexes display significant hydrolytic cleavage of supercoiled pBR322 DNA at pH 7.2 and 37 °C. The hydrolytic cleavage mechanism is further supported by free radical quenching and T4 ligase ligation results. The pseudo-Michaelis–Menten kinetic parameters kcat = 2.13 ± 0.3 h−1 and KM = 5.12 × 10−5 M for macrobicyclic binuclear zinc(II) complex (6) were obtained.

Graphical abstractMacrobicyclic binuclear Cu(II), Ni(II) and Zn(II) complexes [M2L](ClO4)4 display higher rate of phosphate hydrolysis than acyclic mononuclear diamine complexes. The DNA binding and cleavage experimental results show that the mode of interaction of the complexes to calf thymus DNA is groove binding and the complexes can hydrolyzes pBR322 DNA.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Macrobicyclic dinuclear CuII, NiII and ZnII complexes were synthesized. ► All the complexes display significant catalytic activity on phosphate hydrolysis. ► All the complexes are avid DNA binders. ► ZnII complex show better DNA hydrolysis than CuII and NiII analogs.