Role of CA2+ ion in the abortifacient action of prostaglandins. II. Molecular orbital and conformation energy calculations of PGA1

Abstract

AbstractThis paper reports some theoretical studies of PGA1 using conformational and molecular orbital techniques. The conformation energy (CE) calculations, using empirical potential‐energy functions, for intrinsic torsional rotations around C12C13 (θ), C7C8 (Ψ), and C14C15 (ϕ) show a number of energy minima. The relative value of the CE for these minima ranges from 4.09 to 8.01 kcal/mol. An additional rotation around C4C5 (χ) giving “twist” to the carboxyl chains lowers the CE value by 2–3 kcal/mol and a conformation with CE value 2.39 kcal/mol less than crystallographic one is obtained. The interchain interaction energy showed changes with conformations. No significant change in the interchain interaction energy was observed due to “twist” in the carboxyl chain. The isopotential mapping study demonstrated the probable ionic binding site near the carboxyl and the ring (O9) oxygens. Conformational and molecular orbital results are discussed in the light of the reduced abortifacient potency of PGA1 with respect to PGF2α and the possible role of Ca2+ ions in this action.