The role of proton affinity, acidity, and electrostatics on the stability of neutral versus ion-pair forms of molecular dimers

Ion-pair formation via proton transfer from an acidic hydrogen of one functional group to a basic functional group plays an important role in the structure and reactivity of biomolecules in the gas phase. The relative stabilities of the ion-pair and the neutral-pair forms of five dimers composed of a basic molecule and a trifluoroacetic acid molecule were compared using density-functional calculations. The proton affinity of the basic molecules investigated ranged from 246 to 254 kcal/mol. The gas phase acidity of trifluoroacetic acid is 323.8 kcal/mol. The results of the B3LYP (6-311++G**) calculations indicate that the structures of the dimers, change from a neutral pair to an ion pair as the proton affinity of the bases increases, This result is consistent with previous blackbody infrared radiative dissociation experiments on protonated trimolecular complexes (or trimers) consisting of two basic molecules and trifluoroacetic acid, which indicates that the predominant structure of the trimer changes from a charge-solvation structure to a salt bridge structure with the increasing gas phase basicity of the base. The electrostatic character of the interaction between the basic molecule and the trifluoroacetic acid molecule was determined using the natural energy-decomposition analysis (NEDA) program. In the ion pair, a majority (69%-77%) of the attractive energy of the dimer is comprised of the electrostatic component. Two models are derived that include the acidity of the acidic molecule, the proton affinity of the basic molecule, and an electrostatic binding term for both the ion pair and the neutral pair. Several nonelectrostatic interaction terms can be replaced by a single correction or constant term so that both models, one using NEDA electrostatic terms and the other using integration of point-charge interactions, provide reasonably accurate results. This indicates that electrostatic models similar to the ones used here may be useful in studying salt bridge formation in larger molecules. (C) 2001 Elsevier Science B.V.