Ab initio and nonempirical MODPOT/VRDDO calculations on drugs, carcinogens, suspected teratogens, and biomolecules

Abstract

In this paper are presented our recent nonempirical ab initio MODPOTpRDDO calculations on a variety of drugs and biomolecules: nucleic acid constituents, normal neurotransmitters and their metabolites, carcinogens and their activated metabolites, and attack of these on DNA constituents, and suspected teratogens. The M O D P O T~R D D O method incorporates two very desirable options into our own 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 MOD-POT/VRDDO results agree to essentially three decimal places with those of completely ab initio calculations with the same valence atomic basis set. Also included is a discussion of some molecular electrostatic potential contour maps, which in collaboration with Petrongolo were generated from previously calculated ab initio wave functions to illustrate comparisons of such maps from large basis set and minimal basis set ab initio calculations as well as from CNDO wave functions. Such maps allow a cogent comparison of pharmacophores in molecules that exert a similar pharmacological effect by the same mechanism. An example of such a comparison is discussed for electrostatic potential contour maps generated from our previous ab initio wave functions on morphine (a narcotic agonist) and nalorphine (a narcotic agonist-antagonist).