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

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 triazabutadiene that rendered basic upon photoisomerization. The pH an aqueous solution containing water-soluble can be adjusted with 350 nm light. Upon synthesizing soluble in aprotic solvents, we noted similar light-induced change basicity. As proof concept took this photobase and used it catalyze condensation reaction.

Triazabutadienes can be used to readily generate reactive aryl diazonium ions under mild, physiologically relevant conditions. These conditions are compatible with a range of functionalities that do not tolerate traditional ion generation. To increase the utility this releasing chemistry an alkyne-containing triazabutadiene was synthesized. The copper-catalyzed azide–alkyne cycloaddition ("Cu-click") reaction utilized modify and shown nitrogen-rich triazabutadiene. One triazole products...

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

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

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

Aryl diazonium ions are useful across a range of chemical/biochemical areas. These species generally made using strongly acidic conditions, which can be detrimental to acid-sensitive functional groups. The ability generate benzene under basic aqueous conditions is reported herein along with newfound understanding on the reactivity solubilized triazabutadienes whereby π-interactions appear confer large degree stability.

We report a mechanistic study comparing the immune activation of conjugated Toll-like receptor (TLR) agonists and their unlinked mixtures. Herein, we synthesized set six linked dual with different ligands, molecular structures, locations, biophysical characteristics. With these dimers, ran series in vitro cell-based assays, initial overall NF-κB (nuclear factor kappa-light-chain-enhancer activated B cells) activation, cytokine expression profiles, as well time-resolved TNF-α (Tumor Necrosis...

It is unknown if surface bound toll-like-receptor (TLR) agonists activate cells via density or total molecular number. To answer this question, we developed a TLR agonist conjugated polystyrene microparticle (MP) system. Using library of MPs with varying and number, simultaneously observed innate immune cell MP uptake TNFα expression using ImageStream flow cytometry on by basis. The data shows that number not drives cellular activation threshold approximately 105-106 agonists. We believe...

Small molecule immune potentiators (SMIPs) such as imidazoquinolinone derivatives that activate Toll-like receptor (TLR) 7/8 have immense potential vaccine adjuvants and antitumor agents. However, these molecules high bioavailability results in unacceptable levels of systemic inflammation due to adjuvant toxicity, thereby greatly limiting their use. To address this challenge, here we report the design synthesis novel imidazoquinolinone-NF-κB immunomodulator dimers. Employing vitro assays,...

Abstract Small molecule contact allergens are an understudied class of immunostimulatory compounds that have the potential being developed into adjuvants. Vaccines remain most effective tool in preventing disease and adjuvants serve to make vaccines more efficacious by activating innate immunity. To develop molecules as adjuvants, we began first elucidating mechanism allergic hypersensitivity. Using their analogues wanted define structural elements necessary for activation immune cells. Our...