Superoxide dismutase activity of corrole metal complexes

Abstract

The first report regarding SOD activity of metallocorroles, investigated via the combination of the cytochrome C assay, pulse radiolysis, and electrochemistry, is used for identifying the main criteria needed for achieving good performance, as well as for elucidating mechanistic aspects of their action.

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

“…It must be emphasized that the validity of k cat data obtained with cytochrome c assay was confirmed by both pulse-radiolysis study (302) and stoppedflow technique (184,185). The same agreement between these two methods was further confirmed by the Zeev Gross group (99). Over the years, given the lipophilic nature of the major drugs, the biomedical community has been concerned that excessively charged, pentacationic Mn porphyrins would fail to accumulate within the cell at levels sufficient to provide therapeutic effects.…”

“…8) (275). The SODlike activity of this corrole and of other Fe and Mn anionic and cationic corroles, along with Mn(IV)=Mn(III) reduction potentials, has just been reported (99). The first step in a dismutation process, the oxidation of a metal center from þ 3 to þ 4 oxidation state is rate limiting, as opposed to most of the porphyrins, other than biliverdins.…”

SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways

“…5). When translated into experimental data, it appears that E 1/2 for these compounds is identical in either solvent: water or acetonitrile (80,104,196 (28). However, with Mn corroles, the electron-donating groups are required for modifying their E 1/2 from * + 1000 to * + 700 mV versus NHE (196).…”

“…1). Mn(III) corroles do not require oxygen binding to stabilize Mn in higher + 4 oxidation state, whereas Mn in O = Mn IV P is stabilized in + 4 oxidation state with oxygen (80). Axial protonation equilibria for corroles have not been reported.…”

“…The SAR (showed with thick blue line) is valid for many redox-active compounds regardless of their structure: metalloporphyrins, Mn(IV) biliverdins, Mn(III) salens, Mn(II) polyamines, Mn(III) corroles, and Mn(II) aqua complex (271). The E 1/2 values for Mn IV C/Mn III C redox couple (given in Table 1) were determined in phosphate buffer for anionic Mn corrole with two sulfonatopyrrolic groups and three meso pentaphenyl groups, but in acetonitrile for cationic Mn corrole, which bears two meso para-methylpyridyl groups and one meso substituent with derivatized tetrapfluorophenyl group (80,104,196) (Fig. 1).…”