Binding, electrochemical activation, and cleavage of DNA by cobalt(II) tetrakis-N-methylpyridyl porphyrin and its beta-pyrrole brominated derivative

The binding of nucleic acids by water-soluble cobalt(II) tetrakis-N-methylpyridyl porphyrin, (TMPyP)Co, and its highly electron-deficient derivative cobalt(II) tetrakis-N-methyl pyridyl-beta-octabromoporphyrin, (Br(8)TMPyP)Co, was investigated by UV-visible absorption, circular dichroism (CD), and electrochemical and gel electrophoresis methods. The changes of the absorption spectra during the titration of these complexes with polynucleotides revealed a shift in the absorption maxima and a hypochromicity of the porphyrin Soret bands. The intrinsic binding constants were found to be in the range of 10(5)-10(6) M(-1). These values were higher for the more electron-deficient (Br(8)TMPyP)Co. Induced CD bands were noticed in the Soret region of the complexes due to the interaction of these complexes with different polynucleotides, and an analysis of the CD spectra supported a mainly external mode of binding. Electrochemical studies revealed the cleavage of polynucleotides by (TMPyP)Co and (Br(8)TMPyP)Co in the presence of oxygen preferentially at the A-T base pair region. Gel electrophoresis experiments further supported the cleavage of nucleic acids. The results indicate that the beta-pyrrole brominated porphyrin, (Br(8)TMPyP)Co, binds strongly and cleaves nucleic acids efficiently as compared with (TMPyP)Co. This electrolytic procedure offers a unique tool in biotechnology for cleaving double-stranded DNA with specificity at the A-T regions.