With this CAREER Award, the Synthesis Program supports the research of Professor John Jewett of the University of Arizona. Professor Jewett develops new tools for chemical biology that are designed to transform the investigation of protein-protein interactions. This research utilizes an underexplored class of compounds called triazabutadienes; these are structures in which three nitrogens and one carbon are connected in sequence. Triazabutadienes are chemically attached to protein amino acids, followed by spontaneous or enzyme-catalyzed chemical changes which produce a chemical probe. This new chemistry impacts the fields of polymers and materials science. Professor Jewett develops an educational outreach program that focuses on mentoring of students from groups which are underrepresented in science. The project builds connections with a middle school located in a nearby Native American territory. Professor Jewett works with teachers and students to develop culturally-relevant science demonstrations that are shared with younger students. In addition to activities at the middle school, the CAREER Award supports student visits to the University of Arizona campus multiple times each year where researchers interact with graduate and undergraduate chemistry students in science-related activities related to research in the Jewett group. This impacts recruiting of Native American students into STEM careers. This research explores a unique class of compounds that are designed to interrogate protein-protein interactions. Triazabutadienes release highly reactive but chemoselective aryl diazonium ions upon protonation within a physiologically relevant range of pH. First, the triazabutadienes are structurally modified such that they can be initially conjugated to proteins. After conjugation, pH-triggered protein-bound aryl diazonium ions then offer a new way to interrogate protein-protein interactions. Enhanced reactivity which has been observed upon photochemical isomerization of the triazabutadiene expands the utility of these protein-conjugates. Second, the chemistry of triazabutadienes are coupled to cellular chemistry other than acidification. Enzymatically triggered release of triazabutadienes enhances their selective biochemical deployment. Finally, a new class of fluorogenic probes are used to report on the ligation of aryl diazonium species with electron-rich amino acid side chains containing tyrosine and histidine. The chemoselectivity and fluorescence properties of these probes are studied to establish the scope of their utility. In addition to activities at the middle school, the CAREER Award supports student visits to the University of Arizona campus multiple times each year where researchers interact with graduate and undergraduate chemistry students in science-related activities related to research in the Jewett group. This impacts recruiting of Native American students into STEM careers.