Substrate activation for O₂ reactions by oxidized metal centers in biology

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-11, Vol.104 (47), p.18355-18362
• Main Authors: Pau, Monita Y.M, Lipscomb, John D, Solomon, Edward I
• Format: Article
• Language: English
• Subjects: Biochemistry; Biology; Charge transfer; Coordinate systems; Dioxygenases - metabolism; Electronic structure; Electrons; Enzymes; Iron - chemistry; Iron - metabolism; Ligands; Molecules; Orbitals; Oxidation-Reduction; Oxygen - chemistry; Oxygen - metabolism; Perspective; Principal components analysis; Sulfur Dioxide - chemistry; Sulfur Dioxide - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0704191104

The uncatalyzed reactions of O₂ (S = 1) with organic substrates (S = 0) are thermodynamically favorable but kinetically slow because they are spin-forbidden and the one-electron reduction potential of O₂ is unfavorable. In nature, many of these important O₂ reactions are catalyzed by metalloenzymes. In the case of mononuclear non-heme iron enzymes, either FeII or FeIII can play the catalytic role in these spin-forbidden reactions. Whereas the ferrous enzymes activate O₂ directly for reaction, the ferric enzymes activate the substrate for O₂ attack. The enzyme-substrate complex of the ferric intradiol dioxygenases exhibits a low-energy catecholate to FeIII charge transfer transition that provides a mechanism by which both the Fe center and the catecholic substrate are activated for the reaction with O₂. In this Perspective, we evaluate how the coupling between this experimentally observed charge transfer and the change in geometry and ligand field of the oxidized metal center along the reaction coordinate can overcome the spin-forbidden nature of the O₂ reaction.