Biophysical studies on molecular mechanism of abortificient action of prostaglandins I. The study of molecular electrostatic potential distribution of PGF2α, PGF1β and PGA1

Abstract The three-dimensional molecular electrostatic potential mapping for three forms of prostaglandins, viz. PGF 2α , PGF 1β and PGA 1 has been presented using CNDO/II method. The molecule was broken into three overlapping fragments for the sake of calculations and each fragment was treated as an independent molecule. It was observed that even the similar fragments, such as the carboxyl chains of PGF 1β and PGA 1 and hydroxyl chains of PGF 2α and PGA 1 , had quantitative differences in their charge and energy distribution. The total electronic and HOMO energies of the inactive forms (PGA 1 and PGF 1β ) were found to be always lower than that in the active form (PGF 2α ) for these fragments. The shape of the isopotential contours was characterized by the presence of low energy regions around the oxygens and the high energy regions around the carbon atoms, but had quantitative differences. The minimum value of the electrostatic potential E min followed the order PGF 2α 1β 1 which was the reverse of their abortificient activity. Substantial differences were noted in the case of the charge, energy, and electrostatic potential distribution of the ring fragments. They may be relevant for explaining the mechanism of action of these drugs.