Solute Partitioning in Micelles: Combining Molecular Dynamics Simulations, COSMOmic, and Experiments

Abstract

The partition equilibria of solutes between micelles and an aqueous phase is a key factor in many applications. Depending on the task, many micelle-solute combinations are possible. Therefore, theoretical methods to predict the partition behavior in micellar systems are needed. Here, two predictive methods are evaluated and compared. First, it is shown how molecular dynamics simulations (MD) with the umbrella sampling method can be used to calculate free energy profiles in micellar systems. The second applied method is an extension of the COSMO-RS theory to anisotropic systems termed COSMOmic. Both methods are compared by means of free energy profiles and experimental micelle/water partition coefficients. A particular focus is on the partitioning of ionized solutes. As experimental data for partitioning in micelles especially for charged solutes is rare, partition coefficients were also determined experimentally. To get a general understanding of micelles examples of all micelle classes (classified by headgroup charge) are studied: nonionic Triton X-114 (TX114), zwitterionic miltefosine (HePC), anionic sodium dodecyl sulfate (SDS), and cationic cetyltrimethylammonium bromid (CTAB). The free energy profiles of neutral solutes obtained from MD simulations and COSMOmic are in an overall good agreement, and partition coefficients from both methods are in good agreement with experimental data. Depending on the system, the results for charged solutes show some deviations between the methods and experimental data.

Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

“…Studies included the effect of counter-ions, hydrophobic side chain mobility, and interactions with other molecules, as reviewed [60]. Relevant to mutually catalytic networks embodied in amphiphilic micelles (next chapter) are molecular dynamics studies that examine the kinetics and energetics of micelle-related monomer association [61] and dissociation [62,63], as well as solute partitioning into micelles [64]. Likewise, the proposed capacity of micelles to undergo fission is supported by studies on the influence of micelle constituents on micellar morphology, stability, deformation, and disruption [65,66,67].…”

Lessons Learned from the Calculation of One-Dimensional Potentials of Mean Force [Article v1.0]

“…In this article, we focus on one-dimensional PMFs obtained via umbrella sampling simulations for host molecules featuring a distinct hydrophobic cavity. Examples for these types of hosts range from rather low molecular-weight substances such as cyclodextrins [27] or cucurbiturils [28,29], up to large moieties such as micelles [30] or protein channels inside a membrane [31][32][33][34]. The cavity, enabling a ligand to be bound with high affinity and specificity, makes such host molecules attractive for applications in (computer-aided) drug design.…”

Molecular Simulations of Thermodynamic Properties for the Systemα‐Cyclodextrin/Alcohol in Aqueous Solution

“…As a result such calculations have seen a tremendous progress over the last decades and standards are beginning to evolve that allow for reproduction of published results and reduce the barriers to perform such calculations routinely [22 -24]. However, partitioning is not only relevant between homogeneous phases but also between a bulk phase and a heterogeneous phase such as a membrane [25], a micelle [26], a stationary phase in liquid chromatography [27], or a larger biomolecule such as a protein [28]. Therefore, a similar active area of research is the prediction of binding affinities for biomolecular complexes from molecular dynamics simulations due to the expected impact such calculations will have in early stage drug discovery.…”