UC Santa Cruz

Antimony(Sb)-containing molecules have a rich therapeutic history. Their most significant clinical use in modern medicine is in the treatment of the neglected tropical disease leishmaniasis. Up to a million new cases of leishmaniasis are reported annually, and the disease disproportionately affects populations of low- and middle-income countries. The current frontline treatments for leishmaniasis are the pentavalent antimonials: meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam). Although effective, the pentavalent antimonials have severe side-effects and resistance to the drugs is mounting. Despite the pentavalent antimonials having been used for nearly a century, their structures and mechanism of action are still unknown. Elucidation of these drugs’ structures would allow for derivatization that could reduce toxicity while increasing the efficacy of treatment. Furthermore, structural knowledge of the pentavalent antimonials could prove pivotal in the elucidation of their mechanism of action. Presented here are our initial attempts to develop and apply techniques that will allow for better understanding of antimony and its interactions with the ligands employed in the synthesis of the pentavalent antimonials. Quantum theory of atoms in molecules (QTAIM) was used to elucidate the character of bonding interactions between pnictogens and oxygen. Pentaphenylantimony served as a proof-of-concept compound for an exploration into the use of physical inorganic techniques such as X-ray absorption spectroscopy to provide insight to the geometry of Sb-containing compounds. The solution-and solid-state structures of a series of Sb-diolate compounds were investigated via 1H and 13C{1H} nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography to gain a better understanding of how an Sb center is coordinated by secondary and primary alkoxides with varying stereochemistry. Trends in the chemical shifts from NMR spectra of these compounds were observed as a product of the stereochemistry of the diol chelating the Sb center. Elucidation of these spectroscopic signatures allows for future insight into Sb-containing molecules and their structures. The work described in this dissertation provides a foundational framework for understanding the interactions between polyalcohols and Sb, an important step toward improved Sb-containing therapeutics.