Mechanism of Dioxygen Activation in 2‐Oxoglutarate‐Dependent Enzymes: A Hybrid DFT Study

Abstract

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–CO 2 complex, which readily releases the carbon dioxide molecule. The step in which the Fe II–peracid–CO 2 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.