(609g) Molecular Modeling and Simulation of 3-Hydroxybutyric Acid in Aqueous, Ionic Liquid, and Deep Eutectic Solutions

3-hydroxybutyric acid (3HBA) is a key component for biosynthesis and biological activity, as well as a precursor for biopolymer synthesis. While there have been some molecular modeling and simulation studies of 3HBA-based derivatives for biomedical applications, there have been no studies related to biopolymer or bioprocessing applications. In this work, a combination of molecular dynamics and computational quantum chemistry is used to describe the liquid phase thermodynamic and structural behavior of 3HBA in various solutions, including water, synthetic ionic liquids, and deep eutectic solvents.

To describe behavior in aqueous solution, the CHARMM36 force field is used to model 3HBA, while water is modeled by the TIP3P force field. For the 3HBA force field, we determined the necessary electrostatic point charges by using the CHELPG method inside of a Gaussian quantum chemical calculation, utilizing the CBS-Q3 level of theory. These force fields were then deployed in all-atom molecular dynamics simulations to model both the properties and structure of this mixture, with particular attention to the extent of interaction and aggregation between 3HBA-3HBA, HBA-water, and water-water in solution.

In addition, COSMO-based quantum chemical calculations were performed and the COSMOtherm method was utilized to determine infinite dilution activity coefficients of 3HBA in water and a range of different synthetic ionic liquids and deep eutectic solvents. These results are used to provide commentary on possible green chemistry-based solvents for 3HBA extraction during bioprocessing.