New class of artificial enzyme composed of Mn-porphyrin, imidazole, and cucurbit[10]uril toward use as a therapeutic antioxidant

Abstract

In this study, we investigated a new class of artificial enzymes composed of Mn-porphyrin, imidazole, and cucurbit[10]uril (CB[10]) toward therapeutic antioxidants. Structural characterization by means of NMR indicated that the inclusion mode of metalloporphyrin in CB[10] was sensitive to the chemical structure of metalloporphyrin and that the structure of the artificial enzyme had a similarly to that of native heme catalase. Kinetic analysis for catalytic antioxidative activities demonstrated that the artificial enzyme exhibited highly efficient activity for H₂O₂ disproportionation (catalase activity) in water. The activity was classified as top-performing among the water-soluble artificial catalases. The artificial enzyme was constructed by simply mixing the components in water. We consider that this is a great advantage over previously reported artificial catalases, which require a multi-step synthesis or that lack water solubility. The pro-oxidative peroxidase activity was remarkably suppressed due to inclusion in CB[10]. Furthermore, a preliminary in vitro study suggested that the artificial enzyme catalytically eliminated reactive oxygen species, including H₂O₂, in human cell lines. It was presumed that CB[10] contributed to the bioavailability of the artificial enzyme. Overall, the artificial enzyme was shown to have high potential as a therapeutic antioxidant. We consider that the results in this study could lead to a new conceptual advance toward therapeutic antioxidants that could simultaneously improve the catalytic and biological properties of Mn-porphyrins.