Acid–base and electrochemical properties of manganese meso(ortho- and meta-N-ethylpyridyl)porphyrins: voltammetric and chronocoulometric study of protolytic and redox equilibria

Abstract

Growing interest in redox-active compounds as therapeutics for oxidative stress-related diseases led to the design of metalloporphyrins as some of the most potent functional SOD-mimics. Herein we report a detailed electrochemical study of the protolytic and redox equilibria of manganese ortho and meta substituted N-ethylpyridyl porphyrins (MnPs), MnTE-2-PyP⁵⁺ and MnTE-3-PyP⁵⁺, in aqueous solutions. The electrochemical parameters of redox processes for all experimentally available species have been determined, as well as their diffusion coefficients and estimated sizes of aqueous cavities. The results indicate that possible changes of the intracellular acidity cannot affect the antioxidant activity of MnPs in vivo, since no change in the E^0′_app(Mn^IIIP/Mn^IIP) values was observed below pH 10. Furthermore, the results confirm that both of these MnPs can be efficient redox scavengers of peroxynitrite (ONOO⁻), another major damaging species in vivo. This can occur by either single-electron reduction or two-electron reduction of ONOO⁻, involving either the Mn^IVP/Mn^IIIP redox couple or Mn^IVP/Mn^IIP redox couple. In addition to k_red(ONOO⁻) reported previously, the thermodynamic parameters calculated herein imply a strong and identical driving force for the reaction of both ortho and meta isomeric MnPs with ONOO⁻. An enlargement of both Mn^IIIP complexes upon an increase of the solution pH was also observed and attributed to the reduction of positive charge on the central ion caused by deprotonation of the axial water molecules. This expansion of aqueous cavities suggests the formation of a solvent cage and the increased lipophilicity of Mn^IIIP complexes caused by increased electron density on the Mn ion.