Phosphate diesters and DNA hydrolysis by dinuclear Zn(II) complexes featuring a disulfide bridge and H-bond donors

The dinuclear ligand 1 based on the bis-(2-amino-pyridinyl-6-methyl)amine (BAPA) metal binding unit and featuring a two-atom disulfide bridge was synthesized and studied as hydrolytic catalysts for phosphate diesters. The Zn(II) complexes of BAPA are known to elicit the cooperation between the metal ion and the hydrogen-bond donating amino groups to greatly increase the rate of cleavage of phosphate diesters. The reactivity of the dinuclear complex 1$Zn(II)2 toward bis-p-nitrophenyl phosphate and plasmid DNA was investigated and compared with that of reference complexes devoid of the disulfide bridge or of the hydrogen-bond donating amino groups. The dimetallic Zn(II) complex produces remarkable accelerations of the rate of cleavage of both the substrates accompanied by significant differences. In the case of BNP, the presence of the disulfide bridge does not lead to the improvement of the cooperative action of the two metal ions expected as the result of better preorganization. On the other hand, in the case of DNA the complex 1$Zn(II)2 is much more reactive that the corresponding reference devoid of the disulfide bridge. Hence, different requisites must be fulfilled by a good catalyst for the cleavage of the two substrates. Moreover, binding studies with DNA indicated that the presence of two metal ions in the complex or of the pyridine amino groups, but not of the disulfide bridge, results into an enhanced affinity of the complexes toward this substrate.