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

Ab 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 C 9 —O—C 10 epoxide ring both toward C 9 and C 10 for the, most stable β,β,β isomer of BP‐7,8‐dihydrodiol‐9,10‐epoxide. Opening the epoxide ring between C 10 and O leads to a more stable intermediate than opening the epoxide ring between C 9 and C 10 . However, there is no buildup of positive charge in C 10 as has been postulated by some cancer researchers, but rather the C 10 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—C 9 —C 10 or O—C 10 —C 9 angles, there appears to be a possible mixing of configurations that is being investigated further.