Fluorine bonding enhances the energetics of protein-lipid binding in the gas phase.

This paper reports on the first experimental study of the energies of noncovalent fluorine bonding in a protein-ligand complex in the absence of solvent. Arrhenius parameters were measured for the dissociation of gaseous deprotonated ions of complexes of bovine ß-lactoglobulin (Lg), a model lipid-binding protein, and four fluorinated analogs of stearic acid (SA), which contained (X =) 13, 15, 17, or 21 fluorine atoms. In all cases, the activation energies (E(a)) measured for the loss of neutral XF-SA from the (Lg + XF-SA)7⁻ ions are larger than for SA. From the kinetic data, the average contribution of each > CF2 group to E(a) was found to be ~1.1 kcal mol⁻¹, which is larger than the ~0.8 kcal mol⁻¹ value reported for > CH2 groups. Based on these results, it is proposed that fluorocarbon­protein interactions are inherently stronger (enthalpically) than the corresponding hydrocarbon interactions.