Simulating pH titration of a single surfactant in ionic and nonionic surfactant micelles

Calculation of surfactant pK(a)'s in micelles is a challenging task using traditional electrostatic methods due to the lack of structural data and information regarding the effective dielectric constant. Here we test the implicit- and hybrid-solvent-based continuous constant pH molecular dynamics (CpHMD) methods for predicting the pK(a) shift of a lauric acid solubilized in three micelles: dodecyl sulfate (DS), dodecyltrimethylammonium (DTA), and dodecyltriethylene glycol ether (DE3). Both types of simulations are able to reproduce the observed positive pK(a) shifts for the anionic DS and nonionic DE3 micelles. However, for the cationic DTA micelle, the implicit-solvent simulation fails to predict the direction of the pK(a) shift, while the hybrid-solvent simulation, where conformational sampling is conducted in explicit solvent, is consistent with experiment, although the specific-ion effects remain to be accurately determined. Comparison between the implicit- and hybrid-solvent data shows that the latter gives a more realistic description of the conformational environment of the titrating probe. Surprisingly, in the DTA micelle, surfactants are only slightly attracted to the laurate ion, which diminishes the magnitude of the electrostatic stabilization, resulting in a positive pK(a) shift that cannot be explained by chemical intuition or other theoretical models. Our data underscores the importance of microscopic models and ionization-coupled conformational dynamics in quantitative prediction of the pK(a) shifts in micelles.