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 O2− 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, OsO4 is about 60 times more active than Cu,Zn-SOD. The catalytically active couple is OsVIII/OsVII, OsVIII oxidizing O2− to O2 with a bimolecular rate constant of k = (2.6 ± 0.1) × 109 M−1 s−1 and OsVII 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 OsVIII/OsVII redox couple. The OsVIII/OsVII catalyst is stable to biochemicals other than proteins and peptides comprising histidine, cysteine, and dithiols.