Novel Chiral Separation Based on Mixed Conglomerate Crystallization

The Scripps Research Institute, La Jolla CA

Investigators

Abstract

1066608 Blackmond The objective of the proposed research is to develop a novel concept for chiral separations and chiral amplification based on a synergistic combination of two distinct methods for enantioenrichment recently developed in the Blackmond laboratories. This work promises to expand the fraction of chiral compounds currently amenable to separation by crystallization methods. Most chiral compounds crystallize in one of two forms: if the interaction between like enantiomers is preferred, then separate crystals of each hand of the chiral molecule will be formed (known as conglomerates). If heterochiral interactions are preferred, then each crystal will contain a 1:1 mixture of the left and right hands of the chiral molecule (known as racemic compounds). While the former type of compound is clearly more amenable to separation, it is the latter type that is most commonly found in Nature, by about a 10:1 preference. The first part of the current research project seeks ways to alter the phase behavior of chiral compounds to turn racemic compounds into what we term "tunable conglomerates" or "mixed conglomerates". The second part of the project will study how selected candidate systems may evolve from near racemic mixtures of crystals to a single solid enantiomorph through an extension of the "chiral amnesia" process previously demonstrated by this group for simple conglomerate systems. The goal is to demonstrate the emergence of solid phase enantiopurity for each distinct chiral molecule present in the mixture. This work will help to shed light on the fundamental interplay between kinetics and thermodynamics and between physical and chemical rate processes. Most significantly, this research will expand the application of this novel separation method in the pharmaceutical industry. The property of molecular chirality has long fascinated scientists and laymen alike. In addition to its practical aspects, single chirality is part of the mystery of the origin of life on earth. Research in this area becomes a superb conduit for evoking the challenges and joy of science in ways that appeal to young audiences contemplating the study of chemistry, biology, or engineering. We will team with The Scripp Research Institute's (TSRI) multi-faceted Academic Preparation and Outreach Programs by supporting a high school student as a summer research intern in my laboratories. This raises awareness of career opportunities in the biomedical and chemical sciences and fosters an understanding in the general public of the excitement of basic research as well as its connection to our material world. Along these lines a general interest seminar has been developed entitled "How Amino Acids Took a Left-Hand Turn: Probing the Origin of Biological Homochirality". In addition to becoming involved in speaking to and mentoring high school students, faculty advisory lecture series are held with TSRI's Network for Women in Science, involving both professional and personal mentoring to graduate students and postdoctoral fellows.