ABSTRACT
Acids in CLEC ................................................................................................80 3.6.1 Eluent pH ............................................................................................80 3.6.2 Metal Ion Concentration ..................................................................... 81 3.6.3 Type and Amount of Organic Modier .............................................. 81 3.6.4 Type of Metal Ion ............................................................................... 82 3.6.5 Type of Copper Salt ............................................................................ 82 3.6.6 Column Temperature .......................................................................... 82 3.6.7 Flow Rate ............................................................................................ 83
3.7 Covalently Bound Chiral Stationary Phases (B-CSPs) .................................. 83 3.8 Coated Chiral Stationary Phases (C-CSPs) .................................................... 91 3.9 Chiral Mobile Phases (CMPs) ...................................................................... 104 3.10 Computational Approaches in Chiral Ligand-Exchange Chromatography .... 112
3.10.1 Mathematical Models ....................................................................... 113 3.10.2 Molecular Modeling Studies ............................................................ 116 3.10.3 Quantitative Structure Activity Relationship (QSAR) Studies ......... 118
3.11 Conclusion .................................................................................................... 125 3.12 List of Abbreviations .................................................................................... 127 References .............................................................................................................. 129
Different from other chromatographic techniques, the interaction between the chiral selector and the enantiomer in chiral ligand-exchange chromatography (CLEC) does not take place in direct contact. The interaction is mediated by a central metal ion that as a Lewis acid simultaneously coordinates the two species through dative bonds with the following formation of a mixed ternary complex. The absence of a close contact between the selector and the analyte and the presence of a metal cation in the chromatographic environment contribute to the difculty of the rationalization of the chromatographic event, especially when computational approaches are employed for this study. Among the enantiomer chromatographic separation techniques, ligand-exchange has been exploited in all the main ways of accomplishment: chiral mobile phase (CMP), covalently bound chiral stationary phase (B-CSP), and coated chiral stationary phase (C-CSP). Although the rst, commercially available chiral columns were those based on B-CSP, soon after followed by the others, the mechanistic aspects dealing with the chiral recognition and the chromatographic separation process in CLEC are among the less studied ones, most probably because of the complexity of the theoretical models of reference. More recently, this difculty has however spurred different computational approaches with the aim of clarifying the interaction mechanism and indicating the main parameters that describe the analyte responsible for the enantiorecognition process.
