Quantifying the Hydrophobic Effect. 1. A Computer Simulation−Molecular-Thermodynamic Model for the Self-Assembly of Hydrophobic and Amphiphilic Solutes in Aqueous Solution

Abstract

Surfactant micellization and micellar solubilization in aqueous solution can be modeled using a molecular-thermodynamic (MT) theoretical approach; however, the implementation of MT theory requires an accurate identification of the portions of solutes (surfactants and solubilizates) that are hydrated and unhydrated in the micellar state. For simple solutes, such identification is comparatively straightforward using simple rules of thumb or group-contribution methods, but for more complex solutes, the hydration states in the micellar environment are unclear. Recently, a hybrid method was reported by these authors in which hydrated and unhydrated states are identified by atomistic simulation, with the resulting information being used to make MT predictions of micellization and micellar solubilization behavior. Although this hybrid method improves the accuracy of the MT approach for complex solutes with a minimum of computational expense, the limitation remains that individual atoms are modeled as being in only one of two states-head or tail-whereas in reality, there is a continuous spectrum of hydration states between these two limits. In the case of hydrophobic or amphiphilic solutes possessing more complex chemical structures, a new modeling approach is needed to (i) obtain quantitative information about changes in hydration that occur upon aggregate formation, (ii) quantify the hydrophobic driving force for self-assembly, and (iii) make predictions of micellization and micellar solubilization behavior. This article is the first in a series of articles introducing a new computer simulation-molecular thermodynamic (CS-MT) model that accomplishes objectives (i)-(iii) and enables prediction of micellization and micellar solubilization behaviors, which are infeasible to model directly using atomistic simulation. In this article (article 1 of the series), the CS-MT model is introduced and implemented to model simple oil aggregates of various shapes and sizes, and its predictions are compared to those of the traditional MT model. The CS-MT model is formulated to allow the prediction of the free-energy change associated with aggregate formation (gform) of solute aggregates of any shape and size by performing only two computer simulations-one of the solute in bulk water and the other of the solute in an aggregate of arbitrary shape and size. For the 15 oil systems modeled in this article, the average discrepancy between the predictions of the CS-MT model and those of the traditional MT model for gform is only 1.04%. In article 2, the CS-MT modeling approach is implemented to predict the micellization behavior of nonionic surfactants; in article 3, it is used to predict the micellization behavior of ionic and zwitterionic surfactants.

The influence of poly(ethylene glycol) on the micelle formation of alkyl maltosides used in membrane protein crystallization

“…The dehydration term g dehydr accounts for the change in free energy associated with the dehydration of detergent monomers that accompanies the self-assembly into micelles. In the approach by Stephenson et al, 43 g dehydr is further decomposed according to…”

“…43,51,52 In both approaches, the free energy for micelle formation, g mic (in units of k B T), which is the relevant thermodynamic quantity that determines the CMC, is decomposed into various contributions. Only part of these contributions depends on the hydrophobic effect.…”

Molecular dynamics simulation of a polysorbate 80 micelle in water

“…It is not obvious, unlike linear surfactants, as to what conformation this molecule adopts either as a monomer or within a micelle structure in an aqueous environment, how the molecules pack into a micelle, nor the nature of the surfactant-water interface. Knowledge of the micelle structure of this class of surfactant structures is of fundamental interest being required, for instance, for successful applications of molecular-thermodynamic theories, [21][22] and is important for technological applications to enable development and control of formulations on a rational basis.…”

Stabilization of aqueous graphene dispersions utilizing a biocompatible dispersant: a molecular dynamics study

“…The solvent accessible surface areas (SASAs) of the flavin mononucleotide ions and graphene as a function of time was calculated to verify that all the simulations have reached equilibrium. 63,64 From the SASA results (see Fig. S1 in the ESI †), it can be seen that the systems have reached equilibrium after about 80 ns simulation time.…”