Thermodynamics of the hydrophobic effect. I. Coupling of aggregation and pKa shifts in solutions of aliphatic amines Original Research Article

Long aliphatic hydrocarbon chains aggregate in aqueous solution due to the hydrophobic effect, forming structures such as micelles and membranes, while amino groups titrate at basic pH. These two biologically important behaviors are linked in alkylamines, in which the pKa of the amino group is shifted downward by aggregation. In this paper we study the thermodynamics of these coupled processes, following aggregation by observing alkylamine pH titration behavior. The magnitude of the shift depended on the aliphatic chain length and on the concentration of alkylamine: longer chains and higher concentrations lowered the pKa to a greater extent. Gibbs free energies of protonation and aggregation were calculated from the pKa shifts. Enthalpies, entropies, and heat capacities were estimated by vanʹt Hoff analysis from the pKa shift dependencies on temperature. However, the results were less precise than the calorimetrically measured values, as described in the following article. A model to calculate titration curves, pKa shifts, and aggregation of uncharged alkylamines as a function of aliphatic chain length, concentration, and temperature is presented.