| A pressing problem in analytical chemistry is the development of stationary phases for separations that can bind molecules in a selective but reversible fashion. The most challenging of these problems is the resolution of enantiomers, which is becoming of great importance in the pharmaceutical field. The goal of this work has been to create new stationary phases for chiral chromatography, preferably with large scale applications. By using inorganic solids as stationary phases, the solid support can be modified by the intercalation of a chiral selector molecule which has the capacity to distinguish enantiomers based on multi-point non-covalent interactions. Background in chiral separations along with a more general treatment of the previous art in molecular recognition systems is covered in Chapter 1.; In Chapters 2 and 3, the synthesis and characterization of a selected chiral selector-analyte pair, various layered and mesoporous host materials, and intercalated composites are described. Of the materials studied, zirconium phosphate ({dollar}alpha{dollar}-Zr(HPO{dollar}sb4)sb2cdot{dollar}H{dollar}sb2{dollar}O), is the most ideal support. Intercalation of zirconium phosphate with a chiral selector and use of this modified solid in separations is described. The enantiomeric excess achieved approaches the theoretical maximum at high analyte concentration but works poorly at lower concentrations. This concentration dependence was studied by several methods. Also described is the use of this system, under optimized conditions, to perform enantioseparations of unprecedented capacity.; In Chapter 4, the problem of host pre-organization encountered with the initial system was addressed by using a new chiral selector cyclophane. This molecule possesses a rigid, pre-organized binding pocket and incorporates a dipeptide group as the chiral recognition element. This dipeptide can be synthesized as a combinatorial library and thus can address the problems of scale and selectivity simultaneously. These molecules can, in principle, be used to effect recognition of many targeted analytes because the library contains a large number of different selectors. The synthesis and binding characteristics of model cyclophanes and a small library are described. Finally, the behavior of the small library of cyclophanes in binding experiments and the isolation strategies for strongly binding members are discussed. |
