Osmium tetroxide, used in the treatment of arthritic joints, is a fast mimic of superoxide dismutase

Aqueous solutions of osmium tetroxide (OsO₄) have been injected into arthritic knees for the past 45 years to chemically destroy diseased tissue, in a procedure termed "chemical synovectomy." Arthritis is an inflammatory disease. The primary inflammatory chemical species are the superoxide anion radical (O₂^-) and nitric oxide ( ^•NO), which combine to form the peroxynitrite anion (ONOO ^-). Here we show that OsO₄ does not react with ONOO ^- but very efficiently catalyzes the dismutation of O ₂^- to O₂ and H₂O₂. Using the pulse-radiolysis technique, the catalytic rate constant has been determined to be (1.43 ± 0.04) × 10⁹ M^-1 s^-1, independent of the pH in the 5.1-8.7 range. This value is about half that for the natural Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Per unit mass, OsO ₄ is about 60 times more active than Cu,Zn-SOD. The catalytically active couple is Os^VIII/Os^VII, Os^VIII oxidizing O₂^- to O₂ with a bimolecular rate constant of k = (2.6 ± 0.1) × 10⁹ M^-1 s^-1 and Os^VII reducing it to H₂O₂ with a bimolecular rate constant of (1.0 ± 0.1) × 10⁹ M^-1 s ^-1. Although lower valent osmium species are intrinsically poor catalysts, they are activated through oxidation by O₂^- to the catalytic Os^VIII/Os^VII redox couple. The Os ^VIII/Os^VII catalyst is stable to biochemicals other than proteins and peptides comprising histidine, cysteine, and dithiols.