Quantum chemical modeling studies of ethylbenzene dehydrogenase activity

Abstract

AbstractQuantum chemical modeling is used to predict the reactivity of ethylbenzene dehydrogenase (EBDH), a molybdenum enzyme that catalyzes the stereoselective oxidation of alkylaromatic and alkylheterocyclic hydrocarbons to the (S)‐enantiomers of secondary alcohols. The reaction mechanism is studied for four different substrates: ethylbenzene, 4‐ethylphenol, allylbenzene, and 4‐ethylpyridine with a cluster model of the active site. The modeling predicts radical CH activation followed by the formation of a radical intermediate product. Then another electron is transferred to form a carbocation species in TS2, followed by a tightly associated OH rebound step. The modeling study allows qualitative correlation of energy barriers with the results of kinetic assays and identifies factors influencing the chemical reactivity of EBDH with different substrates. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011.