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Molecular calculations with the nonempirical ab initio MODPOT , VRDDO , and MODPOT/VRDDO procedures. XII. Carcinogenic 3‐methylcholanthrene and its metabolites using a MERGE technique
Author(s) -
Hariharan P. C.,
Popkie Herbert E.,
Kaufman Joyce J.
Publication year - 1981
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560200307
Subject(s) - ab initio , chemistry , computational chemistry , ab initio quantum chemistry methods , molecule , organic chemistry
Ab initio MODPOT/VRDDO/MERGE calculations were carried out on carcinogenic 3‐methylcholanthrene (3‐MCA) and its metabolites. The results for 3‐MCA were compared to our earlier similar calculations for carcinogenic benzo(a)pyrene (BP). Both compounds 3‐MCA and BP are carcinogenic and are metabolically activated by similar mechanisms but in different positions. Both the calculated wave functions for 3‐MCA and BP and the electrostatic molecular potential contour maps generated from these wave functions correctly reflect the similarity of mechanisms of metabolic activation and the differences in position. Our calculated results both for BP and for 3‐MCA reflect accurately their experimentally observed behavior. Thus this combination of theoretical techniques can be used with confidence to describe the behavior of the polycyclic aromatic hydrocarbons (PAH's) and their metabolites. The ab initio 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 analysis 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 our recent MERGE technique which allows reuse of integrals from a common skeletal fragment was used. The ab initio MODPOT/VRDDO/MERGE calculations were carried out for 3‐MCA, 3‐MCA oxides, 3‐MCA dihydrodiols, and 3‐MCA dihydrodiolepoxides. The metabolites investigated were 3‐MCA 9,10‐oxide; 3‐MCA 7,8‐oxide; 3‐MCA 9,10‐dihydrodiol [ trans (axial, axial); trans (equatorial, equatorial); cis (axial, equatorial); cis (equatorial, axial)]; and 3‐MCA 9,10‐dihydrodiol–7,8‐epoxide [for both conformations A and B of the dihydrodiol and for all stereoisomers of the dihydrodiolepoxides relative to below and above the plane: ααα, and ααβ αβα αββ βαα βαβ ββα and βββ (most stable)]. Calculations were also carried out for opening of the C 7 OC 8 epoxide ring both towards C 7 and C 8 for the most stable isomer Aβββ (above the ring). Opening the epoxide ring between C 7 and O leads to a more stable intermediate than opening the epoxide ring between C 8 and O. Again, however, as with opening the epoxide ring in BP 7,8‐dihydrodiol–9,10‐epoxide there is no buildup of positive charge on C 7 in the 3‐MCA metabolites as postulated by some cancer researchers, but rather the C 7 becomes slightly more negative. Nor is there a buildup of negative charge on the O atom, but rather it becomes slightly more positive. As the epoxide ring is opened further than 90° for the OC 7 C 8 or OC 8 C 7 angles, there appears to be a possible mixing of configurations that is being investigated further.