Making radical clocks run faster: Complexation of the 2-norcaranyl radical to the “naked” lithium cation lowers the barrier to the “radical-clock” rearrangement (see picture). However, model calculations on the mechanism of the hydroxylation of norcarane with cytochrome P450 suggest that no such electrostatic catalysis can be expected at the active site of the enzyme.
Density-functional theory (DFT) and ab initio calculations have been used to investigate the effect of a complexed lithium cation on the radical-clock rearrangement of the 2-norcaranyl radical to the 3-cyclohexenylmethyl radical. As found earlier for ring-closing radical clocks, complexation with a metal ion leads to a significant lowering of the barrier to rearrangement. DFT calculations on a model for the norcaranyl clock in cytochrome P450 confirm the two-state reactivity proposal of Shaik et al. and indicate that the porphyrin exerts little or no electrostatic effect on the rearrangement barrier.