Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: A hybrid DFT study

The reaction mechanism for dioxygen activation in 2-oxoglutarate-dependent enzymes has been studied by means of hybrid density functional theory. The results reported here support a mechanism in which all chemical transformations take place on a quintet potential-energy surface. More specifically, the activated dioxygen species attacks the carbonyl group of the co-substrate producing the Fe-II-persuccinate-CO2 complex, which readily releases the carbon dioxide molecule. The step in which the Fe-II-peracid-CO2 complex is formed is found to be rate-limiting and irreversible. Subsequent heterolysis of the O-O bond in the Fe-II-persuccinate complex proceeds in two one-electron steps and produces the high-valent iron-oxo species Fe-IV=O, which is most likely to be responsible for oxidative reactions catalyzed by 2-oxoglutarate-dependent enzymes. The concerted pathway for simultaneous O-O and C-C bond cleavage on the septet potential-energy surface is found to be less favorable. The relative stability of different forms of the active iron-oxo species is assessed, and the quintet five-coordinate complex is found to be most stable.