A catalyst-free bioorthogonal reaction for malononitrile addition to azodicarboxylates.

ABSTRACT: Developing bioorthogonal reactions that enable fundamental exploration of biological processes remains a key pursuit of chemical biology. We report here malononitrile addition to azodicarboxylate as a distinct class of catalyst-free bioorthogonal reactions. Our findings demonstrate that malononitriles react rapidly with azodicarboxylates in both organic and aqueous environments at ambient temperature, without requiring catalysts, bases, or additives. The facile modification of malononitriles facilitates their incorporation into biomolecules such as RNA and proteins. This malononitrile addition to azodicarboxylate reaction exhibits high robustness in complex biological systems, attributed to its distinct reactivity through a concerted transition state. Furthermore, we find that the malononi

SUBMITTER: Huang H 

PROVIDER: S-EPMC12589507 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature