Synthesized pharmaceutical drugs often yield in racemic mixtures. The enantiomers produced are similar in atomic connectivity, but their spatial orientations differ. This directly affects their functionality and interactions with biologically active molecules. Furthermore, one enantiomer may produce the desired medicinal effect, whereas the other may be detrimental. This calls for the establishment and optimization of enantiomeric separation processes. Previous studies have shown that Micellar Electrokinetic Chromatography (MEKC) can be utilized to separate enantiomeric compounds using Amino Acid-Based Molecular Micelles (AABMMs) as the pseudo-stationary phase. Further investigation reveals that the alteration of the AABMM dipeptide polar head constituent largely affects its formation and effectiveness as a chiral recognition medium. To holistically understand, compare, and predict the effectiveness of different AAMBBs, the creation of a quantitative structure-enantioselective retention relationships (QSERR) database must be established. In working towards the development of this database, this research is focused on using molecular dynamics simulations of AABMMs, in conjunction with chiral compounds, to gain insight into the factors responsible for enantiomeric separation. The AABMMs being investigated are composed of the undecyl form of all dipeptide combinations using L- alanine, valine, and leucine, as well as achiral glycine. Experimental MEKC results were compared to the computational binding free energy calculations to validate this model. The QSERR database, which will be developed from this study, will allow for the comparison and screening of chiral compounds in AAMBB systems.

In silico screening of chiral compounds in amino acid-based molecular micelle systems using molecular dynamics simulations

ACS Fall 2020 Virtual Meeting

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