Enzymatic transformations of aliphatic carbon centers generally require cleavage of strong C–H bonds. High-valent transition-metal-oxo complexes represent "Nature's heavy artillery" for initiating such reactions.1,2 Formation of metal-oxo enzyme intermediates from reduced transition metal cofactors and O2 requires two electrons, often provided by a co-substrate such as 2-(oxo)glutarate, NADPH, or ascorbic acid. In this modus operandi, the provision of two electrons by the co-substrate precludes oxidation of the primary substrate by more than two electrons in a single event. Our recent investigations of several mononuclear and dinuclear non-heme-iron enzymes (with our many collaborators) have revealed cases in which C–H bonds, partially activated by the presence of a heteroatom with a lone pair on the target carbon, are instead cleaved by mid-valent metal-superoxo complexes formed by the simple addition of O2 to the reduced transition metal cofactors.2-5 These complexes are Nature's "light tactical weaponry,"2 and they expand the range of possible outcomes, most notably to include four-electron-oxidations by a single equivalent of O2. In this presentation, I will highlight chemical mechanisms that we have uncovered within this specialized manifold for O2 and C–H activation, rationalize the unique capabilities that it enables, and consider cases for which others have proposed that it could be operant. References 1) Krebs, C.; Galonic, D.; Walsh, C. T.; Bollinger, J. M., Jr. "Non-Heme Fe(IV)-Oxo Intermediates," Acc. Chem. Res., 2007, 40, 484-492. 2) Bollinger, J. M.; Jr., Krebs, C. "Enzymatic C-H-Activation by Metal-Superoxo Complexes," Curr. Opin. Chem. Biol. 2007, 11, 151-158. 3) Bollinger, J.M., Jr.; Diao, Y.; Matthews, M.; Xing, G.; Krebs, C. “myo-Inositol Oxygenase: a Radical New Pathway for O2 and C-H Activation at a Nonheme Diiron Cluster,” Dalton Trans., 2009, 2009, 905-914. 4) van der Donk, W. A.; Krebs, C.; Bollinger, J. M., Jr. "Substrate Activation by Iron Superoxo Intermediates," Curr. Opin. Struct. Biol., 2010, 20, 673-683. 5) Wörsdörfer, B.; Lingaraju, M.; Yennawar, N.; Boal, A.K.; Krebs, C.; Bollinger, J. M., Jr.; Pandelia, M.-E.; “Organophosphonate-degrading PhnZ reveals an emerging family of HD-domain mixed-valent diiron oxygenases” Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 18874-18879.

Mechanisms and purview of C-H-bond activation by mid-valent metal superoxide complexes

251st National Meeting (2016)

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