Part 1: Synthesis, characterization, and hydrolysis of silicate ester prodrugs: model studies Part 2: Amide bond formation kinetics in the selective uptake of aliphatic amines in PEG-PLGA block-copolymer nanoparticles.

Abstract

The research presented in this thesis comprises two main projects: model studies for the synthesis, characterization and hydrolysis of silicate ester prodrugs, including a fluorescent model (Part 1), and amide bond formation kinetics to analyze the selective uptake of amines into polymer nanoparticles (Part 2). In Part 1 an array of trimenthoxy monoacyloxy orthosilicates were synthesized and the relative hydrolysis rates were measured. It was observed that extending the linear carbon chain on the acyloxy group changed the relative rate constants by less than an order of magnitude while adding more bulky side chains (isopropyl and tert- butyl) gave relative rate constants that stretched a full order of magnitude. I also outline the synthesis and fluorescence of a nitrobenzoxadiazole silicate ester and initial loading experiments of the fluorophore into polymer nanoparticles. In Part 2 I outline an experimental design that probes the selective uptake of amines to form amide bonds within PEG-PLGA nanoparticles. When two dialkylamines were competed a higher selectivity was observed for the more hydrophobic amine.