Molecular calculations with the nonempirical ab initioMODPOT, VRDDO, and MODPOT/VRDDO procedures. IX. Carcinogenic benzo(a)pyrene and its metabolites using a MERGE technique

Abstract

AbstractAb initio MODPOT/VRDDO calculations have been carried out on carcinogenic benzo(a)pyrene and its metabolites. The MODPOT/VRDDO method incorporates two very desirable options into our fast ab initio Gaussian programs: MODPOT—ab initio effective core model potentials—and a charge‐conserving integral prescreening approximation which we named VRDDO (variable retention of diatomic differential overlap). For orbital energies and population analyses the MODPOT/VRDDO results agree to essentially three decimal places with completely ab initio calculations using the same valence atomic basis set. For this series of very closely related congeners a new MERGE technique was implemented that allows reuse of integrals of a common skeletal fragment. Since our program computes integrals efficiently by blocks, reusing information common to the block, it was more difficult to implement a MERGE technique than for integral programs which calculate the integrals one‐byone. The MODPOT/VRDDO calculations were performed for benzo(a)pyrene (BP), BP oxides, BP dihydrodiols, and BP dihydrodiol epoxides. The metabolites investigated were BP‐7,8‐oxide, BP‐4,5‐oxide, BP‐7,8‐dihydrodiol [cis(e, a), cis(a, e), trans(e, e), and trans(a, a)], and BP‐7,8‐dihydrodiol‐9,10‐epoxide [β,β,β (the most stable), β,β,α; α,α,β, and α,α,α all derived from cis‐BP‐7,8‐dihydrodiol and β,α,β; α,β,β and α,β,β derived from trans‐BP‐7,8‐dihydrodiol]. Several different conformations were calculated for each of the BP dihydrodiols and BP dihydrodiol epoxides. Calculations were carried out for the opening of the C9—O—C10 epoxide ring both toward C9 and C10 for the, most stable β,β,β isomer of BP‐7,8‐dihydrodiol‐9,10‐epoxide. Opening the epoxide ring between C10 and O leads to a more stable intermediate than opening the epoxide ring between C9 and C10. However, there is no buildup of positive charge in C10 as has been postulated by some cancer researchers, but rather the C10 becomes slightly more negative. Nor is there a buildup of negative charge on the O atom. rather it becomes slightly less negative. As the epoxide ring is opened further than 90° for the O—C9—C10 or O—C10—C9 angles, there appears to be a possible mixing of configurations that is being investigated further.