Molecular Simulations of 12-Hydroxystearic Acid and Its Derivatives in Organic Solvent
Authors:   , Gordon Ryan , Abrams Cameron F. 
Published: July 2021

12-Hydroxystearic acid (12HSA) and its derivatives are well-known organogelators, and they play critical roles in a variety of applications. Under gelating conditions, 12HSA forms a three-dimensional network of fibers with lateral fibril dimensions on the submicron scale. It is hypothesized that layers of 12HSA molecules stack to produce a multilamellar structure with alignment of 12-hydroxyl groups that form a chain of hydrogen bonds, and the twist of the fibers is due to the nonlinearity in the carbon chain at the 12th carbon. Furthermore, the sense of twist is sensitive to both the size of the carboxylate counterion and the chirality at the 12th carbon. However, the details underlying these differences are difficult to infer from low-resolution information available from, for example, X-ray scattering. In this thesis, we detail the use of molecular dynamics (MD) simulations to identify key functional group interactions that impact the morphology of aggregates of 12HSA and its derivatives, and to assess the importance of optical purity at the 12th carbon and form of the head-group on aggregate structure. First, in order to assess the aggregate morphology, we conducted MD simulations on microsecond-long time scales for (R)-12HSA at 12.5 wt % in explicit hexane solvent. Self-assembly was accelerated by using a modified force field to prohibit alkane chain dihedral gauche states and then verified by continuation using standard force-field parameters. In three independent simulations, acceleration using a "gauche-less'' force field resulted in self-assembled ordered aggregates through formation of polarized five- and six-membered rings between inter-12-hydroxyl groups and head-to-head carboxylic acid dimerization. When subjected to the unmodified dihedral force field, two of the three structures remained stable after 1 microsecond of MD. Stable structures exhibited a "ring-of-rings'' motif, composed of two six-membered acetic acid-dimerized ring bundles with six satellite rings, while unstable structures did not. These structures displayed scattering peaks that agreed with experiment, which suggests this "ring-of-rings'' structure could be a primary feature of (R)-12HSA in organic solvents. Next, we studied the effect of optical purity on the aggregate structures of 12HSA. We conducted microsecond long MD simulations on (1) (R)-12HSA, (2) (S)-12HSA, and (3) a 50/50 racemic mixture, each solvated at 12.5 wt % in explicit hexane. The "full-cycling'' method described previously was used for these simulations. Similarly to the optically pure (R)-12HSA aggregates, (R)-12HSA aggregates observed the same ring-of-rings motif. However, the chirality at the 12th carbon dictates the overall twist of the rings and thereby the handedness of the rings. Racemic mixtures did not produce stable ordered aggregates, likely due to insufficient enantiomerically pure ring formation. Next, we analyze the impact of the head-group counterion on aggregate morphology by testing systems of optically pure 12-hydroxystearate with both lithium-carboxylate and sodium-carboxylate head-groups. Due to difficulties with the TraPPE-UA force-field in observing correct ion-carboxylate dimer complexes predicted by quantum mechanical results that showed the high stability of dimer complexes compared to undimerized states, we created predefined dimer complexes based on structures from quantum mechanical calculations. The lithium-carboxylate system exhibited two stable dimer forms: (1) centrally symmetric and (2) diagonally symmetric, while the sodium-carboxylate system only had a diagonally symmetric dimer. We found that similar to the acid systems, all of the ion 12-hydroxystearate systems had inter-hydroxyl hydrogen bonds that were oriented in a ringlike fashion. However, we found that the centrally symmetric dimer allowed for a higher frequency of inter-hydroxyl hydrogen bonds than that of the diagonally symmetric systems, due to its ability for the head groups to pack more easily. Finally, we attempted to find the self-assembly mechanism of 12HSA and its derivatives. We opted to use umbrella sampling with a 1D collective variable (CV) that would influence the alkane dihedral configuration. Multiple CVs were studies, but the most practical CV developed was an indirect control of the alkane dihedral conformation by controlling the distance between carbons 1 and 12. This method had difficulty predicting a free-energy minimum due to time scale constraints. Further enhanced sampling methods should be tried, such as replica-exchange MD (REMD).