Multiscale Computational Investigation of the C-H Activation Reactivity of Engineered Myoglobin

Abstract

The current thesis reported a combined MD and QM/MM investigation for the C-H activation reactivity of wild-type and three reconstituted myoglobin. We have tried to unravel the reactivity of myoglobin reconstituted with Mn porphycene [rMb(MnPC)]. Along with it, we also explored why the reconstituted iron porphycene [rMb(FePC)] is not reactive. From the MD analysis, it was observed that the substrate ethyl-benzene is not stable in the active site of [rMb(FePC)], whereas it is sufficiently stable in the pocket of [rMb(MnPC)]. This may be linked with the reactivity of the [rMb(MnPC)]. Axial histidine ligand (HIS93) might also play an important role in the reactivity here, as in the case of [rMb(MnPC)], it goes far away from the central Mn porphycene. QM/MM investigations show that rMb(MnPc)'s active Mn(IV)=O species extract hydrogen atoms in a similar way to the CYP450's Cpd I species, and the triplet state is more favorable than the singlet state.