Ground State Conformations and Entropic and Enthalpic Factors in the Efficiency of Intramolecular and Enzymatic Reactions. 1. Cyclic Anhydride Formation by Substituted Glutarates, Succinate, and 3,6-Endoxo-Δ4-tetrahydrophthalate Monophenyl Esters

Abstract

Intramolecular and enzymatic reactions require conformations in which the orbitals of reactants are properly aligned and van der Waals surfaces are in a near-attack conformation (NAC). Much of the changes in steric and electrostatic energies that take place in moving from the favored ground state conformation (FGSC) to the transition state are accounted for when the NAC has been assumed. Upon assessing the steric, electrostatic, and zero point energies, one is in position to calculate the probability of NAC formation. Using a series of monoesters of dicarboxylic acids, we have (i) created, via stochastic search, 10 000−40 000 minimized conformations per ester; (ii) chosen only the unique local minima conformations for each ester; (iii) determined the energies of each minimum conformation using MM3(92); (iv) identified the geometry of the NACs where the van der Waals overlap has not begun for the approach of carboxyl anion and ester carbonyl; and (v) calculated the mole fraction (probability, P) of each es...