COMPARISON OF QUANTUM-MECHANICAL METHODS TO COMPUTE THE BIOLOGICALLY RELEVANT REACTIVITIES OF CYCLOPENTA-POLYCYCLIC AROMATIC-HYDROCARBONS

In computational studies to understand the interaction of polycyclic a romatic hydrocarbons (PAHs) with biomolecular systems, the semiempiric al method AM1 has been used previously to determine the geometry of th e PAH and its metabolites and relevant intermediates. A number of stud ies have shown that AM1 provides geometries for parent PAHs that are a cceptably close to experimentally determined structures. However, many of the properties that determine the manner by which PAHs interact wi th biological nucleophiles depend on the structure of metabolites and reactive intermediates where less experimental information is availabl e. In a previous study, we used AM1 to obtain the molecular geometries of reactive intermediates of cyclopenta-PAHs (cPAHs) and then used si ngle-point Hartree-Fock calculations, with the Gaussian 3-21g basis se t, to obtain molecular energies and charge distributions, in order to predict the direction of epoxide ring opening. Recent advances in the availability of computational hardware and software have provided othe r, more rigorous, methods for approaching this problem. In this study, we used Hartree-Fock methods in the Gaussian series of programs emplo ying the 3-21 g and 6-31 g basis sets and the local density functiona l method Dmol to obtain molecular geometries, energies, and charge dis tributions of the epoxides and the two potential hydroxycarbocations t hat could result from protonated ring opening, for a series of cPAHs. We have also performed the same calculations with AMSOL/SM2, a semiemp irical method that adds the effect of the aqueous environment to the A M1 Hamiltonian. The division of the cPAHs into classes is not altered by these more rigorous calculations. The inclusion of water in the Ham iltonian has a greater effect on the results than using the ab initio methods to obtain the structure. (c) 1994 John Wiley & Sons, Inc.