UCLA

This dissertation describes advancements in the controlled delivery of boron-based cargo through the use of both small molecules as well as nanomaterials to tune both the distribution and concentration of boron content delivered in vivo. Specifically, we employ the use of various closo-dodecahydrododecaborate derivatives for encapsulation with ferumoxytol nanoparticles, boron-oxide based nanoparticles with varied capping groups, and small molecule analogues of histone deacetylase inhibitors. We have shown that boron-rich materials can be delivered to tissues with a range of favorable concentrations and that this delivery can be affected through the manipulation of chemical structure of the cargo and nanocarrier structure. Chemical advances to improve control of the delivery of boron are crucial for advanced work with neutron-based reactions, including boron neutron capture therapy.Chapter One provides an introduction to the use of neutrons and known reactions with chemical systems. This provides brief historical and background details as well as a perspective on the potential for future developments in chemical reactions involving neutrons. Chapter Two demonstrates the noncovalent interaction between several closo-dodecahydrododecaborate derivatives with ferumoxytol, an iron oxide-based nanoparticle system. Ferumoxytol is able to encapsulate a range of boron cluster derivatives and through a combination of in vitro and in vivo kinetic analyses, we show that encapsulation can favorably affect the biodistribution of boron-rich clusters. Chapter Three describes a laboratory scale synthesis for a well-studied compound employed in boron neutron capture therapy. [B12H11SH]2- (BSH) was previously difficult to prepare due to a combination of multi-step reactions as well as the necessity for large excesses of reagents. Chapter Three also highlights the compatibility of BSH with Au- and Pd-based organometallic species that have been used in the modification of carbon-based thiols. Chapter Four reports the biodistribution of several derivatives of boron oxide-based nanoparticles. We find that the size and chemical structure of the nanoparticle capping group can serve as a guide for future derivatives. Chapter Five describes the development of boron cluster pharmacophores, specifically two small molecule histone deacetylase inhibitors. The biodistribution of these species and their comparison to state of the art histone deacetylases is included. Chapter Six demonstrates the use of the closo-hexaborate cluster as a nucleophilic boron cluster reagent for the preparation of small molecules containing B–C bonds.