Manganese–porphyrin and –salen complexes have revolutionized the treatment of cancer based given their remarkable dual ability to function as both (1) chemotherapeutics that directly kill cancer cells, and (2) chemoprotectants that directly protect healthy cells against damage caused by radiation therapy. This duality arises from a common intermediate, namely a high-valent Mn–oxo species that can oxidize (a) harmful reactive oxygen species (ROS) into more benign species (e.g., H2O2 à ½ O2 + H2O) or (b) other biomolecules, such as DNA, in a way that leads to cell death. Whether a Mn-based redox therapeutic will cause or prevent cell death is determined by the local conditions surrounding that complex in that specific biological environment, which makes it difficult to predict in advance whether that complex will function as a chemotherapeutic or chemoprotectant in a targeted medicinal application. An additional complication is that the highly-oxidizing nature of the high-valent Mn–oxo species can also lead to complex decomposition, with the reported turnover number (TON) values being limited to ≤ 25.1. Our group has previously reported an organoruthenium complex (Ru1) that can reduce radicals at biologically-relevant potentials using, as terminal reductants, any biomolecule that contains a CH–OH moiety, and even H2O2 itself. Herein we detail the catalytic disproportionation of H2O2 into ½ O2 + H2O by Ru1, in aerobic aqueous media, with turnover frequency (TOF) and TON values of 1.09 s–1 and ≥ 4000, respectively. In addition, Ru1 exhibits a catalase/peroxidase selectivity ratio (C/P) of 8.58 × 103 to 1. Impressively, the TOF, TON, and C/P values for Ru1 are 11.9-, 120-, and 89.2-fold greater than the highest values reported for any Mn–porphyrin or –salen redox therapeutic.

New possibilities in redox therapeutics with an organometallic catalase mimic that exhibits exceptional stability and ultralow competing peroxidase reactivity

ACS Spring 2022

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