MSE Colloquium - Dr. Gregory A Stephenson
Date: April 27, 2012 from 2:00 pm to 3:00 pm EDT
Location: Room 214, S. W. Mudd
Contact: For further information regarding this event, please contact Wesley Hattan by sending email to wjh2121@columbia.edu or by calling 2128547860.
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Gregory Stephenson, Eli Lilly and Company

Symmetry Breaking in Crystallizations:  Different Polymorphic Selection by R- and S- Enantiomers in Achiral Media
(Missing polymorph of the Melatonin Agonist)

This talk will describe the pair-wise study of two enantiomers of a melatonin agonist compound. The inactive enantiomer crystallized initially as a metastable polymorph, but on its fourth synthesis recrystallization resulted in a much more stable, monotropically related polymorph. The active enantiomer, however, has yet to be crystallized in the stable polymorphic form despite more than one thousand attempts, many at the multi-kilogram scale. The energy difference for these two polymorphs borders the exceptional, 0.7 kcal/mol at room temperature. As a result of this large energy difference and the metastable form being "stalled" in its metastable state, many interesting features can be observed that could not have been otherwise. The metastable polymorph of the active enantiomer converts to a monohydrate form at room temperature, whereas the stable polymorphic form of the inactive enantiomer does not and is less soluble than the monohydrate form in water at room temperature. If the "missing polymorph" of the active enantiomer were to nucleate, it is predicted that spontaneous resolution of the racemic compound into a conglomerate mixture of separate R- and S- crystals of the stable polymorphic form at slightly sub ambient temperatures. The "missing polymorph" of the melatonin agonist serves as a reminder of the important role that primary nucleation plays in dictating crystallization outcome and how the appearance of a new form can change the "experimentally accessible" crystal form landscape of a compound.

Greg Stephenson was born in Anderson Indiana in 1962. After obtaining a B.S. in Chemistry from Ball State University, he earned a Ph.D. in Medicinal Chemistry from Purdue University for research of the solid-state properties of pharmaceuticals under the advisement of Professor Stephen Byrn. He subsequently joined Eli Lilly and Company in its Material Science and Physical Characterizations group in 1994. He is currently a Research Advisor to the Preformulation Department, where he is responsible for the company's small molecule X-ray crystallography laboratory and its Salt Screening groups. He was the recipient of Eli Lilly and Company's Presidential Award in 1995, 1997, and 2004. He has authored more than 50 peer-reviewed journal articles, is named as co-inventor on 11 different patents, and has authored three book chapters. He was elected as a Fellow of the International Centre for Diffraction.  He serves on the Editorial Advisor Board for The Journal of Pharmaceutical Sciences and reviews articles for numerous journals.He continues to be fascinated by the crystallization behavior of organic compounds and continues to venture into the laboratory on every possible opportunity.