Computational studies of the interaction of 1,1-dimethylallyl cation with benzene reveal that its potential energy surface has a rich complexity. The lowest energy π-complex, which involves binding of both ends of the cation to the benzene ring, is calculated to be 4.5 kcal mol−1 lower in energy than its related σ-complex. The results provide further support for the idea that π complexation of carbocations is stronger over the periphery of aromatic systems, and offer insight into why biological reactions involving this type of carbocation do not lead via σ-complex formation to electrophilic substitution of the aromatic rings in proteins.

Computational analyses, using primarily density functional theory, have been used to determine the stabilization associated with the carbocation–π interaction of a biochemical carbocation intermediate binding to a phenylalanine residue in an enzyme active site. Studies of complexation between t-butyl cation and ethylbenzene, and of a model of a carbocation intermediate with a phenylalanine in the active site of geranyl diphosphate C-methyl transferase, have afforded the first quantitative evaluation of the stabilization that can be provided to a carbocation by an aromatic residue in an enzymatic reaction. Describing the hydrophobic surrounding medium using a dielectric constant between ε = 2 and ε = 4, the calculated carbocation–π stabilization energy lies in the range of 10–7.5 kcal mol−1.