Design and Synthesis of Advanced Materials for Separation Science

Chromatography is one of the fundamental means of separating compounds for analytical purposes as well as large-scale purification. Stationary phases are highly advanced materials that must be produced with carefully controlled physical dimensions and surface chemistry. Developing fields of scientific inquiry drive the need for new, more capable stationary phases that take advantage of new technology. Chapter 1 gives an overview of the basic materials used as solid supports for high performance liquid chromatography, their means of production, and the chemistry used to modify their surfaces. Application of the recently developed copper-catalyzed azide-alkyne cycloaddition reaction to surface modification of stationary phase materials is introduced in this context. The design of new stationary phases is usually an empirical process, but as computing power has advanced, modeling the interactions between compounds in solution and the stationary phase is becoming more important. Chapter 2 describes computational studies on an important chiral pharmaceutical and describes a possible highly discriminating chiral selector for this compound. Application of new reactions to the development of stationary phases is an important means of advancing their capabilities. Chapters 3, 4, and 5 describe the application of the copper-catalyzed azide-alkyne cycloaddition reaction to the surface modification of organic and inorganic materials to produce stationary phases for a variety of chromatographic modes. Chapter 3 concerns the initial application of this reaction to the preparation of HPLC stationary phases by modifying porous methacrylate beads for reversed phase and affinity chromatography. Chapter 4 describes the adaptation of this reaction to the in situ modification of silica beads and macroporous monoliths to produce a chiral stationary phase. In Chapter 5, the reaction is further applied to the in situ modification of organic polymer monoliths in fused silica capillaries to produce cation exchange, affinity, and reversed phase materials. To increase the density of long alkyl chains bonded to the surface of the reversed phase sorbent, the use of aliphatic polyester dendrons with long alkyl peripheries as linkers is explored. The key intermediate in the copper-catalyzed azide-alkyne cycloaddition is a copper alkynide species. In the course of the above work, there was a need to prepare a trimethylsilyl protected terminal alkyne and an attempt was made to use the same copper alkynide species as an intermediate in the silylation process. This reaction has not been extensively explored before and Chapter 6 describes some studies performed to gain insight into the direct copper-catalyzed silylation of terminal alkynes.