Collaborative Research: Design of Templated Ceramic Materials for Separation and Purification of Complex Carbohydrates

Complex carbohydrates play many integral roles in biological systems. Biologically active polysaccharides (glycans) interact with proteins on the outside of cells, and are involved in controlling communication, adhesion, and transport of material between cells. The need to isolate and purify specific carbohydrates for use as drugs has emerged from the realization that carbohydrates are central to many cell functions and disease states, ranging from cold sores to cancer. However, the technology to synthesize and purify specific carbohydrates is falling behind the ability of glycobiologists to identify the structure and function of carbohydrates. This project will develop microphase-directed molecular imprinting (MOMI) of sol-gel ceramic materials to design selective, stable materials for the separation and purification of complex carbohydrates based on recognition of the glycan building blocks of glucose, glucosamine, and glucuronic acid. In MOMI, imprinting sites are anchored on the surface of self-assembled surfactant micelles, and sol-gel polymerization of metal oxide precursors and organically modified silanes create a material complementary to the imprinting sites. The micelles reduce the need for solvents during processing, stabilize the material during drying, and serve as welldefined pore templates that can be removed after curing to make the imprinted sites accessible. A well designed MOMI process is hypothesized to produce materials that selectively adsorb the complex carbohydrate for which the imprinting sites were designed. This collaborative project employs the expertise of chemical and materials engineering and synthetic chemistry to focus synergistically on three critical aspects of the development of the MOMI process for molecules with acidic (glucuronic acid) and basic (glucosamine) functionality. The first aim addresses control of the interactions between material precursors and imprinting molecule to create a perfect binding pocket. The second aim addresses the design and predictive synthesis of a matrix to support the imprinted sites based on knowledge of surfactant phase behavior and interactions. The third aim addresses the synthesis of the imprinting molecules themselves - specifically, molecules that effectively play dual roles as pore templates and molecular imprinting sites. Each one of these aims begins from currently accessible experimental systems and builds in complexity as milestones are reached toward the ultimate goal of imprinting complex polysaccharides. Intellectual merit - The molecular imprinting of ceramics through dual-use pore templating/molecular imprinting molecules is potentially transformative to the development of high performance adsorbents for the separation of functional polysaccharides. By combining the synthetic versatility of sol-gel materials and the selectivity of molecular imprinting, the proposed work will establish approaches to customizing ceramics through the knowledge of imprinting and carbohydrate binding mechanisms. Mimicry of the highly selective "lock and key" interaction between glycans and proteins within synthetic sol-gel matrices will be developed for the isolation of biologically relevant polysaccharides.