THERMODYNAMIC DESCRIPTION OF A CONTACT AND SOLVENT-SEPARATED ION-PAIRAS A FUNCTION OF SOLVATION - A MODEL FOR SALT BRIDGES AND PROTON-TRANSFER REACTIONS IN BIOLOGY

Solvation free energies for abeta-methylbicyclo[4.4.0]decane-7alpha-ca rboxylic acid (1), a cis-decalin amino acid that populates two conform ers in which either an intramolecular contact or solvent-separated ion pair is formed, have been determined in a wide range of solvents (CDC l3 to D2O). The nature of the ion pairs, and the range of conditions e valuated, mimicked ion pairs found in biomolecules (''salt bridges''). Conformational and proton-transfer equilibria were evaluated from cha nges in H-1 NMR coupling constants and chemical shifts, respectively, and the ion pair DELTAGs could be extracted directly. Correlations of ion pair DELTAGs with solvent polarity scales (E(T)(30) values) and so lvent hydrogen bond acidities demonstrated the importance of stabilizi ng the carboxylate ion in low-polarity solvents. Comparisons of ion pa ir stability for contact and separated ion pairs revealed that the ele ctrostatic attraction is secondary to relative solvent dielectric and hydrogen bond acidity at stabilizing the interaction; conversely, solv ent hydrogen bond basicity did not contribute to the stabilization. Th e failure of bulk solvent properties, such as the Kirkwood-Onsager die lectric epsilon(K), to adequately correlate ion pair energetics (and p reviously, hydrogen bond energetics: Beeson, C.; Pham, N.; Shipps, G.; Dix, T. A. J. Am. Chem. Soc. 1993, 115, 6803) indicated the limited a pplicability of macroscopic electrostatic models; rather, the correlat ions between electrostatic DELTAGs and empirical solvent parameters am plified the need for molecular solvation models. Ultimately, the sensi tivity of electrostatics to solvent donor-acceptor properties argues t hat a successful treatment of protein structure must be done on the mo lecular level, by evaluating local interactions and solvation. The res ults thus have significance for a description of electrostatic interac tions in biological structure and function.