A Fukui function overlap method for predicting reactivity in sterically complex systems

A formalism is given for predicting reactivity of complex systems by combin ing electronic structure calculations with forcefield calculations within a transition state theory framework. The theory is employed in combination w ith the Fukui function to produce a simulation method capable of the ensemb le sampling needed to examine sterically complex systems. An important link age between reactivity information and energetic quantities is provided by introduction of the Fukui overlap integral. This spatial overlap integral m easures the coincidence of electron donating regions on a nucleophile with electron accepting regions on the corresponding electrophilic reactant. We show that configurations with high values of this overlap integral tend to have lower density-functional theory energies. Thus, Fukui functions calcul ated once on single isolated reactants can be used to quickly estimate the reactivity of configurations generated using conventional forcefield-based simulations. The correlation between energies and high overlap integrals ca n also be used to identify initial guess configurations for transition stat e searches. However, in the present implementation, real transition states are not accessible because intramolecular geometry relaxation is not allowe d. The proposed method is tested on electrophilic aromatic alkylation react ions. Simulation results successfully reproduce experimental substituent ef fects in a series of variously substituted aromatics. Especially encouragin g is the ability of the simulations to predict steric effects in the reacti on of toluene with a series of electrophiles of varying bulkiness. Further applications, previously inaccessible to simulation, are expected in system s where steric effects play a dominant role in determining reaction selecti vity. (C) 2001 American Institute of Physics.