UC Santa Cruz

The chemistry of the heavier pnictogens has shaped medicine for centuries, from the earliest therapeutic applications to the modern use of pnictogen compounds in treating infectious disease and the emergence of radioisotopes for diagnostic imaging and targeted radiotherapy. Despite this rich history, many aspects of heavier pnictogen chemistry remain incompletely understood, particularly the relationships between molecular structure, electronic properties, and chemical reactivity in complex biological environments. Addressing these fundamental questions is essential for the rational development of next-generation pnictogen-based therapeutics, diagnostics, and ligand design.This dissertation investigates fundamental aspects of arsenic, antimony, and bismuth chemistry through four complementary studies spanning historical medicinal chemistry, redox reactivity, coordination chemistry, and ligand design. First, the long-debated structure of Ehrlich's arsphenamine is revisited through a critical examination of historical evidence and modern structural characterization, providing a new perspective on one of medicinal chemistry's most influential compounds. Second, a series of arylarsonic acids are examined as redox-activated prodrugs to elucidate how electronic structure governs reduction kinetics, ligand exchange, and biological activity, establishing structure-reactivity relationships that inform the design of modern arsenic therapeutics. Third, the synthesis and characterization of small molecule tricysteinylpnictines are explored as simplified models for understanding the coordination environments of arsenic, antimony, and bismuth in sulfur-rich proteins, providing insight into the structural principles that underlie biological recognition and reactivity. Finally, principles of hard–soft acid– base chemistry are applied to the development of new chelators for heavy pnictogens, with the goal of enabling the stable coordination of medically relevant radioisotopes for future imaging and therapeutic applications.Collectively, this dissertation illustrates that common themes link seemingly disparate problems in heavier pnictogen chemistry. These studies establish fundamental structure-reactivity relationships that provide a foundation for future advances in medicinal, biological, and radiochemical applications of the heavier pnictogens.