ChirBase database has been employed to mine the chemical structures of compounds resolved on common commercial chiral stationary phases (CSP). Different data sets were produced. The molecular fingerprint (enantiophore) strategy was then applied over these data sets. Enantiophores are identified by analyzing and mapping the three-dimensional common structural features shared by the ligand molecules imported from ChirBase. Such lists of encoded ligand enantiophores allowed us to generate 3D maps of the molecular interacting fragments, which are supposed to act reciprocally with each CSP. Results show that each CSP is combined with different preferential enantiophore counterparts in the ligand. These differences may be well related to the particular behavior of a given CSP to separate different families of compounds. As expected, supramolecular cellulosic or amylosic CSPs show generalist behavior by resolving a wide range of racemates. On the other hand, molecular CSPs based on a well-defined chiral receptor (such as Whelk-O1 or Chirobiotic T) appear to be more specific and thus specially adapted for more restrictive families of compounds. In addition, enantiophore analyses confirm that the supramolecular CSPs can combine multiple potential binding sites and so offer numerous enantioselective mechanisms toward a ligand. Inversely, on molecular CSPs, the ligand must respect strict geometrical constraints to make possible the chiral discrimination. Additional applications of the methodology are discussed as well.
2004 Wiley-Liss, Inc.