The NLRP1 and CARD8 inflammasomes detect reductive stress.

The danger signals that activate the related nucleotide-binding domain leucine-rich repeat pyrin domain-containing 1 (NLRP1) and caspase activation and recruitment domain-containing 8 (CARD8) inflammasomes have not been fully established. We recently reported that the oxidized form of TRX1 binds to NLRP1 and represses inflammasome activation. These findings suggested that intracellular reductive stress, which would reduce oxidized TRX1 and thereby abrogate the NLRP1-TRX1 interaction, is an NLRP1 inflammasome-activating danger signal. However, no agents that induce reductive stress were known to test this premise. Here, we identify and characterize several radical-trapping antioxidants, including JSH-23, that induce reductive stress. We show that these compounds accelerate the proteasome-mediated degradation of the repressive N-terminal fragments of both NLRP1 and CARD8, releasing the inflammasome-forming C-terminal fragments from autoinhibition. Overall, this work validates chemical probes that induce reductive stress and establishes reductive stress as a danger signal sensed by both the NLRP1 and CARD8 inflammasomes.

Calculated oxidation potentials predict reactivity in Baeyer-Mills reactions.

Azobenzenes are widely used as dyes and photochromic compounds, with the Baeyer-Mills reaction serving as the most common method for their preparation. This transformation is often plagued by low yields due to the formation of undesired azoxybenzene. Here, we explore electronic effects dictating the formation of the azoxybenzene side-product. Using calculated oxidation potentials, we were able to predict reaction outcomes and improve reaction efficiency simply by modulating the oxidation potential of the arylamine component.

A Modular Approach to Arylazo-1,2,3-triazole Photoswitches.

Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.