| A variety of cellular receptors have enhanced binding to frameworks with a multivalent expression of a single epitope, such as carbohydrates. In order to explore complex binding phenomena, a diverse selection of synthetic and naturally occurring molecules have been researched as scaffolds for the multiple display of a biologically relevant motif. The most useful cores for scaffolds are those that have particular geometrical parameters (e.g., size, shape, symmetry) to allow unique ligand presentation. The focus of this research project has been to develop the use of cube-octameric polyhedral oligosilsesquioxanes (R8Si8O12) as scaffolds for the presentation of biologically relevant motifs.; At the beginning of this project, only a few silsesquioxane frameworks were available with reactive pendant substituents that were suitable for use as scaffolds, and there were no frameworks available that could couple biologically relevant groups. In order to prepare new silsesquioxane frameworks containing functionality suitable for coupling groups of biological interest (e.g., amine, alcohols or carboxylic acids) we have explored the synthetic modification of (CH2=CH)8Si8O12 (1) and (HCl·H2NCH2HC2CH2) 8Si8O12 (12·8HCl). The vinyl groups of 1 can be synthetically transformed by olefin cross-metathesis and UV-catalyzed photoaddition of polar substituted thiols. The amine groups of 12 react with a variety of electrophilic reagents, allowing the synthesis of new octafunctional frameworks in high yields. Compound 12 can also be functionalized with N-protected amino acids and biologically active carbohydrate-derived lactones. The strong and selective bindings of these carbohydrate-functionalized silsesquioxanes are determined using carbohydrate binding proteins.; In order to create more complex and dynamic scaffolds, which may serve as site-specific drug-conjugates, it is necessary to have peripheral group differentiation. We have explored the selective functionalization of R 8Si8O12 frameworks from two methods. First, the reaction of 1 with a deficient amount of triflic acid produces a mixture of partially functionalized beta-triflates (e.g., (CH2=CH) 8-n(TfOCH2CH2)nSi8O 12) frameworks. These beta-triflates can then react with nucleophiles to produce new mixtures of beta-substituted products. Monofunctionalized products, such as (CH2=CH)7(HOCH2CH 2)Si8O12, can be isolated using normal phase chromatography, and may be used to couple groups of biological relevance. Second, the selective cage cleavage of 1 with strong aqueous base affords (CH 2=CH)8Si8O11(OH)2. Condensation of this disilanol with R'(Me)SiCl2 produces a nine-silicon containing silsesquioxane R8R'(Me)Si 9O13, which has a single differentiated pendant substituent. |
