The Gibbs Energy–Potential Energy Conundrum and Chemical Reactivity: Implications for Catalysis and Enzyme Action

Abstract

The interpretation of transition state theory via reaction energy profiles is problematical, as it remains unclear whether the energy being represented is the Gibbs energy or the potential energy. Although transition state theory is formally an extension of classical equilibrium theory, employing the Gibbs energy can lead to ambiguities in explaining reactivity trends and differences. Thus, the differential reactivity of the carbonyl group in carboxylic esters and carboxylic acid chlorides, when present in the same molecule, can only be explained by invoking transition state effects because of the common ground state. The said transition state effects, however, apparently need implausible assumptions. It is argued herein that these ambiguities can be avoided by employing potential energy. In particular, by invoking the “localized” potential energy at a reactive center, ground state effects can be brought into play. This is likely to be largely vibrational potential energy, as this is closely involved in bond breaking and making. It appears, therefore, that transition state theory is best viewed in a qualitative sense for it to be practically meaningful. These arguments, in fact, have intriguing implications for catalysis, particularly the theory of enzyme catalysis. Thus, enzymes apparently possess large negative Gibbs energies of formation, hence their reactivity cannot be explained by ground state effects. However, if the “localized” potential energy of the reactive groups in the active site is considered, the phenomenal reactivity of enzymes becomes comprehensible, in an alternative to the Pauling hypothesis of transition state stabilization. This generally implies that the action of catalysts needs to take into account the ground state potential energy of the catalyst, which is almost always ignored in current theoretical treatments.