450
M. G. Quesne and S. P. de Visser
Fig. 5 Active site region of P450 cam , from PDB 2CPP with heme in purple and substrate (camphor)
in amber
Scheme 2 Alternative hydroxylation and desaturation pathways
work that used a combination of: DFT, QM/MM, and valence bond (VB) modeling
techniques to help answer this fundamental question [61].
In order to quantify the effect of substrate driven chemoselectivity, small DFT
models of the first coordination sphere of the Fe(IV)=O center of Cpd I were used
to study its reaction mechanism(s) with: valpronic acid (VA), ethane (ET), and dihydroanthracene (DHA) [61]. In vitro enzymatic studies [91] have shown that P450
catalyzed oxidation of ethane promotes exclusive alcohol formation, while DHA is
desaturated to form anthracene and VA can go through either the hydroxyl rebound
or desaturation pathways. The minimal DFT cluster models did predict the experimentally observed exclusive alcohol formation; however, when the VA and DHA
substrates were used the calculations predicted both possible pathways to be bar-
M. G. Quesne and S. P. de Visser
Fig. 5 Active site region of P450 cam , from PDB 2CPP with heme in purple and substrate (camphor)
in amber
Scheme 2 Alternative hydroxylation and desaturation pathways
work that used a combination of: DFT, QM/MM, and valence bond (VB) modeling
techniques to help answer this fundamental question [61].
In order to quantify the effect of substrate driven chemoselectivity, small DFT
models of the first coordination sphere of the Fe(IV)=O center of Cpd I were used
to study its reaction mechanism(s) with: valpronic acid (VA), ethane (ET), and dihydroanthracene (DHA) [61]. In vitro enzymatic studies [91] have shown that P450
catalyzed oxidation of ethane promotes exclusive alcohol formation, while DHA is
desaturated to form anthracene and VA can go through either the hydroxyl rebound
or desaturation pathways. The minimal DFT cluster models did predict the experimentally observed exclusive alcohol formation; however, when the VA and DHA
substrates were used the calculations predicted both possible pathways to be bar-