High throughput multiplexed method for evaluation of enantioselective performance of chiral selectors by HPLC-ESI-MS and dynamic titration: cinchona alkaloid carbamates discriminating N-blocked amino acids.
Because of the generally different interaction of enantiomers with biological systems, there has been an ever increasing demand for artificial highly enantioselective systems that can facilitate separation processes involved in the research and development of enantiomerically pure drugs. Such systems may be discovered by large-scale screening of compound libraries which warrants rapid and cost-efficient screening methods. Here, we demonstrate enantioselectivity determination for systems of cinchona alkaloid carbamates and N-blocked amino acids using HPLC-MS and the recently developed dynamic titration technique (Frycák P, Schug KA. Anal Chem 2008;80:1385-1393). A mixture of nine N-blocked amino acids (either D or L enantiomers) was separated on a reversed-phase column with cinchona alkaloid carbamates added postcolumn. Dissociation constants of the observed noncovalent complexes were determined from the HPLC-MS data. Enantioselectivity was then calculated from the dissociation constants, pointing out the best performing systems. For these systems, apparent dissociation constants were measured for the whole range of enantiomeric composition and were shown to obey a proposed theoretical model.
Frycák
Petr
P
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019-0065, USA.
Schug
Kevin A
KA
D000596:Amino Acids / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002930:Cinchona Alkaloids / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D017186:Titrimetry / Q000379:methods*
D000596:Amino Acids; D002219:Carbamates; D002930:Cinchona Alkaloids