Flora W. Kimani

Water‐Soluble Triazabutadienes that Release Diazonium Species upon Protonation under Physiologically Relevant Conditions

Triazabutadienes are an understudied structural motif that have remarkable reactivity once rendered water-soluble. It is shown that these molecules readily release diazonium species in a pH-dependent manner in a series of buffer solutions with pH ranges similar to those found in cells. Upon further development, we expect that this process will be well suited to cargo-release strategies and organelle-specific bioconjugation reactions. These compounds offer one of the mildest ways of generating diazonium species in aqueous solutions.

A Photobasic Functional Group.

Controlling chemical reactivity using light is a longstanding practice within organic chemistry, yet little has been done to modulate the basicity of compounds. Reported herein is a triazabutadiene that is rendered basic upon photoisomerization. The pH of an aqueous solution containing the water-soluble triazabutadiene can be adjusted with 350 nm light. Upon synthesizing a triazabutadiene that is soluble in aprotic organic solvents, we noted a similar light-induced change in basicity. As a proof of concept we took this photobase and used it to catalyze a condensation reaction.

Light-Activated Triazabutadienes for the Modification of a Viral Surface.

Chemical crosslinking is a versatile tool for the examination of biochemical interactions, in particular host–pathogen interactions. We report the critical first step toward the goal of probing these interactions by the synthesis and use of a new heterobifunctional crosslinker containing a triazabutadiene scaffold. The triazabutadiene is stable to protein conjugation and liberates a reactive aryl diazonium species upon irradiation with 350 nm light. We highlight the use of this technology by modifying the surface of several proteins, including the dengue virus envelope protein.

Protecting triazabutadienes to afford acid resistance

Recent work on triazabutadienes has shown that they have the ability to release aryl diazonium ions under exceptionally mild acidic conditions. There are instances that require that this release be prevented or minimized. Accordingly, a base‐labile protection strategy for the triazabutadiene is presented. It affords enhanced synthetic and practical utility of the triazabutadiene. The effects of steric and electronic factors in the rate of removal are discussed, and the triazabutadiene protection is shown to be compatible with the traditional acid‐labile protection strategy used in solid phase peptide synthesis.