Nelu Grinberg, Ph.D.
Distinguished Scientist, Chemical Development, Beohringer Ingelheim Pharmaceuticals

"New Advances in Chromatographic Separation"

Bio:

Dr. Nelu Grinberg is a Distinguished Scientist in the Chemical Development Department at Boehringer Ingelheim Pharmaceuticals in Ridgefield, CT.  Prior to this, he worked for sixteen years in the Analytical Department at Merck Research Laboratories in Rahway, NJ, where he was a Senior Research Fellow.  He has authored and coauthored over 80 publications, including articles and book chapters.  He is currently on the editorial board of the Journal of Liquid Chromatography and Related Techniques and is a Co-editor of the Advances in Chromatography series. He is also the President of Connecticut Separation Science Council, Course Director for a Short Course on Separation of Enantiomers at the Eastern Analytical Symposium and member of the Board of Directors of the Society of Small Molecule Science.  Dr. Grinberg obtained his Ph.D. in Chemistry from the Technical University of lasi in Romania. He conducted postdoctoral research with Professor Barry Karger at Northeastern University and with Professor E. Gil-Av at The Weizmann Institute of Science in Rehovot, Israel.

Abstract:

The advances in fast LC can be primarily attributed to developments in the column and instrumental technologies. The demand for screening more and more samples in the fields of proteomics, genomics, etc., drove HPLC to new domains. Smaller particle size, along with the development in the instrumentation, made possible to quickly perform separations which in the past took a long time to achieve. Fused core technology is one of the recent advances in stationary phase manufacturing which led to development of fast and spectacular chromatographic methods. This talk will focus on two parts: first, the use of fused core technologies to in process monitoring and second, the enantiomeric separation.

Chiral separation has entered its maturity phase. At this time there are over sixty types of chiral phases on the market capable of binding with a pair of enantiomers through a wide variety of interactions ranging from hydrogen bonding, inclusion interaction, p-p interactions, and ion pairing to ligand exchange interactions. With so many interactions to take advantage of, the possibility of achieving enantiomeric separation becomes a matter of understanding their nature and the conditions which govern them as determined by the mobile phase composition.

Polysaccharide phases are among the most versatile phases for the separation of enantiomers. Their versatility stems from their steric configuration, as well as the substitution at the hydroxyl functional groups. Unfortunately, there is a lack of understanding of the interaction of these biopolymers with pairs of enantiomers, which makes the development of enantioseparation methods a matter of trial and error. Our laboratory undertook the task of understanding such separations, starting with the structural changes occurring in the presence of solvents (which constitutes the mobile phases in chromatography) and in the presence of enantiomeric analytes.

Amylose tris(3,5-dimethylphenyl)carbamate (ADPC) and cellulose tris(3,5-dimethylphenyl)carbamate (CDPC) are two of the most effective chiral stationary phases for the separation of enantiomers. The retention of enantiomers on these chiral stationary phases is dominated by hydrogen bonding, while the enantioselectivity is governed by other kinds of interactions, (e.g. inclusion in the calyxes which exists along the ADPC and CDPC chains, as well as p-stacking). Vibrational circular dichroism (VCD) is a relatively new technique which allows the examination of chiral compounds at the molecular level. We used this technique in order to understand the behavior of these polymers during the enantiomeric separation process. The influence of different solvents on the enantiomeric separation of N-,O-blocked amino acids will be examined upon their separation.