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

Abstract

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.

Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues

“…Triazabutadienes are stable scaffolds used to release diazonium ions under mildly acidic conditions. 100 The synthesis and applications of triazabutadienes for specific derivatization and conjugation of Tyr residues have been widely discussed in the literature. 13 Moreover, recently, the palladium-catalyzed Suzuki reaction of triazobutadienes has been reported.…”

Protein Modification via Mild Photochemical Isomerization of Triazenes to Release Aryl Diazonium Ions

“…Previous work within our lab has focused on applications of a unique class of π-conjugated triazenes known as triazabutadienes (TBDs) as masked aryl diazonium ions for bioconjugation applications. , These scaffolds have been shown to be markedly bench stable, and their reactivity can be tuned to release aryl diazonium ions within various conditions, most commonly with the introduction of mild acid, or irradiation with UV light . They also have many unique advantages including the ability to be functionalized with orthogonal handles, such as alkynes or fluorophores for imaging applications. , The limitation that remains with TBD chemistry is the lack of synthetic ease.…”