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 ester present as NACs. The values of log k(rel) for the intramolecular reactions of each ester are a linear function of log P with slope = 1. Using the most energetically stable ground state conformation and the lowest energy NAC for each ester, values of Delta H degrees directly correlate to Delta G double dagger, while Delta S degrees has no correlation with Delta G double dagger. Like results were obtained when the phase space of the system was taken into account. Thus, the rate constants of these intramolecular reactions find quantitative explanations in the distribution of ground state conformations, such that the free energy of activation is determined by Delta H degrees. In a trajectory from most stable ground state to the transition state, these features will become evident in the lowering of the transition state energy. The conformations of the monoesters of the dicarboxylic acids are considered in detail.