My Way and Conceptual Reflections on the Development of Enantioselective Chiral Ion Exchangers for LC

To date the analytical up to preparative scale separation methodologies of enantiomers via LC has reached maturity. It includes the analysis of individual enantiomers of drug substances but also of metabolites and endogenous compounds in complex sample matrices. An arsenal of diverse chiral stationary phases (CSPs) and “chiral” columns of various providers is available as a result of pioneering developments paired with the elucidation of the underlying enantioselectivity principles in connex to their operational modii. Strategically, Enantioselectivity is based on a three-dimensionally driven intermolecular interaction concept of a so-called chiral selector (SO) moiety, intrinsically provided by the CSP, and the chiral selectands ((R )-SA and (S)-SA), the analytes, via intermediate diastereomeric associates which need to be sufficiently different in energy in order to obtain resolution of enantiomers. Our conceptual focus along that line concentrated on the development of chiral ion exchanger type CSPs of which at least one of the multiple interactions sites between the SO and the SAs need to be oppositely charged to establish an ion pairing via strong electrostatic forces in concert with additional SO-SA interactions to fulfill the sterical requirements to reach chiral resolution. Following this vision and long-time “chiral” experience we and partners reached a set of chiral anion, cation and ampholytic ion-exchanger of various SO structure motifs and demonstrated the versatility of this concept in theory and practice. All these CSP materials are characterized by exceptional features and work particularly well for very polar e.g. hydroxy acids, and even ampholytic compounds as e.g. free amino acids and peptides. On the basis of selected examples I will present “my way” of developing diverse chiral ion-exchanger type CSPs, particularly of the Cinchona based type SO motifs and discuss the stereoselective molecular recognition mechanism in theory and practice.