This award supports the work of Professors Erin Johnson and Jason Hein at the University of California-Merced. Isolation of chiral molecules as pure enantiomers remains a challenge for synthetic chemistry. Highly stereoselective reactions (eg. chiral catalysts or chiral auxiliaries) have been developed; however, these represent only a subset of reactions and do not offer general solutions. Methods relying on physical separations (eg. enantioselective crystallizations) have the potential to be more broadly applicable. A combined theoretical and experimental study of the phase equilibria of chiral compounds will be employed to allow development of enatioselective crystallization methods. This approach will use density-functional theory combined with the exchange-hole dipole moment dispersion model to predict energy differences between homochiral and heterochiral crystal forms. These results will be used to guide the development of a coupled-vessel preferential crystallization method, capable of resolving racemate-forming compounds and providing a new approach to crystal-induced asymmetric synthesis.
Most chemical reactions produce products in their mirror images. However, many drugs are active in only one ("chiral") form, and often the mirror images ("enantiomers") of these molecules can themselves be toxic. Thus methods for either direct synthesis, or more generally, for separation of the two enantiomers is essential. This study will broaden the understanding of intermolecular interactions between chiral molecules and represents a first step toward establishing general, reliable methods for the synthesis and separation of crystalline chiral molecules. Isolation of chiral molecules as individual enantiomers is a critical goal for the fine-chemical and pharmaceutical industries. This work has the potential to greatly expand synthetic strategies to produce molecules of 100% enantiomeric purity.
