DFT study of substituent effects in the hydroxylation of methane and toluene mediated by an ethylbenzene dehydrogenase active site model

Density functional theory (DFT) was applied to mimic active species of ethylbenzene dehydrogenase (EBDH), a molybdoenzyme. Considering the impact of several aspects including transition metals, Bronsted-Lowry acid/base conjugate pairs, the trans effect, and supporting ligands upon the relevant activation barriers for methane and toluene led to conclusions that, on average, the transition states for methane activation/functionalization are roughly 13 kcal/mol higher than those for toluene, which reflects the difference in homolytic C-H bond enthalpies for methane and toluene (Delta(BDE) similar to 16 kcal/mol). For the seven different methane functionalization catalysts, the average free energies for the H-atom abstraction (HAA) and radical rebound transition states are 36 +/- 15 and 41 +/- 17 kcal/mol, respectively, with the Cr complexes being toward the lower end of these ranges, and the heavier Mo and W oxo complexes being closer to the upper end. The analysis of the free energies indicates that the energies of the two transition states and the intermediate that lies between them are all positively correlated, thus synthetic strategies to reduce one barrier should positively impact to the other. Among the various chemical parameters, the impact of metal and organic substrate was seen to be more significant than the impact of acid/base conjugate pair, trans ligand and supporting ligand substituents. (C) 2018 Elsevier B.V. All rights reserved.