I-N Electronic Structure of a Molecule in Solution

Trans and gauche conformational equilibria in the side chains of aspartic acid (Asp) and asparagine (Asn) were investigated by measuring the vicinal spin-spin coupling constants of 1H NMR in acidic, neutral, and basic aqueous solutions over a wide range of temperature (5–90 ̊C). The standard free-energy changes ∆G0 were obtained for the trans to gauche conformational variations on the Cα–Cβ bond with respect to the α-carboxyl group and the β-carboxyl group in Asp (β-amide in Asn) and were decomposed into enthalpic ∆H0 and entropic-T∆S0 components. The hydration of ionic and polar groups in Asp competes against the large intramolecular electrostatic repulsion energy and stabilizes the gauche more than the trans conformer in correspondence to a larger degree of separation of positive and negative partial charges. In the neutral solutions, where both the carboxyl groups are negatively ionized, the hydration part even overwhelms the intramolecular repulsion and leads to a negative ∆H0. The fact that the hydration almost cancels the intramolecular electrostatic repulsion contradicts the widely accepted view that the trans preference in the conformational equilibrium is due to the intramolecular repulsion between α-CO2and β-CO2(or β-CONH2).