Cleavage of DNA by Electrochemically Activated Mn-III and Fe-III Complexes of meso-Tetrakis(N-methyl-4-pyridiniumyl)porphine

Electrochemical methods were used to activate Mn-III and Fe-III complexes of meso-tetrakis(N-methyl-4-pyridiniumyl)porphine (H2TMPyP) to cause cleavage of pBR322 DNA and to study their interaction with sonicated calf thymus DNA. Electrochemical reduction of (MnTMPyP)-T-III and (FeTMPyP)-T-III (at low concentrations) in the presence of 02 was required to activate these complexes. However, (FeTMPYP)-T-III at 1 X 10(-6) M produced DNA strand breakage without being electrochemically reduced. At low concentrations, (FeTMPyP)-T-II was more efficient at cleaving DNA than (MnTMPyP)-T-II. Reduction of 02 at a platinum electrode also produced some cleavage but to a much smaller extent. The oxidized form of (MnTMPyP)-T-III (charge 5+) has higher affinity for sonicated calf thymus (CT) DNA than the reduced form (charge 4+), as determined by the negative shift in E degrees' for the voltammetric wave in the presence of DNA. Both forms of (FeTMPyP)-T-III (charge 4+) interact with DNA to about the same extent. Differential pulse voltammetry was used to determine binding constants (K) and binding-site sizes (s) of the interaction of these metalloporphyrins with sonicated CT DNA. The data were analyzed assuming both mobile and static equilibria. (MnTMPyP)-T-III binds to DNA (5 mM Tris, 50 mM NaCl, pH 7) with K = 5 ( +/- 2) X 10(6) M-1, s = 3 bp (mobile) or K = 3.6 (+/- 0.3) X 10(6) M-1, s = 4 bp (static). (FeTMPyP)-T-III at that ionic strength caused DNA precipitation. At higher ionic strength (0.1 M Tris, 0.1 M NaCl, pH 7), (FeTMPyP)-T-III associates to DNA with K = 4.4 (+/- 0.2) X 10(4) M-1, s = 5 bp (mobile) or K = 1.9 (+/- 10.1) X 10(4) M-1, s = 6 bp (static).