Expanding Triazabutadiene Applications Beyond Tyrosine and Histidine Reactivity

Abstract

This thesis aims to expand the applications of diazonium ion chemistry beyond its traditional use in modifying tyrosine and histidine residues. Central to this work is the use of triazabutadienes (TBD), which serve as latent diazonium ion precursors capable of controlled activation under mild conditions.A major outcome of this work is a proof of concept for a pro-fluorogenic triazabutadiene. The design of this novel class of probes combines three key features relevant to advancing tools in chemical biology: logic gated systems, biological activation, and fluorescence-based reporting. In parallel, a new class of triazabutadienes was synthesized to generate alkyl diazonium ions – an underexplored but highly reactive species. These were shown to covalently label proteins, highlighting their potential for proximity labeling and other applications where short-lived, spatially restricted reactivity is desired. Finally, a series of exploratory studies support ongoing research efforts and point toward several key opportunities for expanding the capabilities of diazonium ion-based chemistry.