The development of bioorthogonal chemical reactions—chemical reactions that can be conducted in living cells—has been one of the most significant areas of advancement in chemistry in recent years. Bioorthogonal reactions that join molecules together, such as “click chemistry,” have created a revolution in biomedical research. However, there are fewer bioorthogonal reactions that can split molecules. Franzini and colleagues have developed a series of highly efficient chemical reactions, termed “dissociative bioorthogonal reactions”, that do just that. These new reactions hold promise for enabling new targeted therapies and highly-sensitive diagnostic tools.
Bioorthogonal removal of 3-isocyanopropyl groups enables the controlled release of fluorophores and drugs in vivo. Tu J, Xu M, Parvez S, Peterson RT, Franzini RM. J Am Chem Soc. 2018 Jul;140(27):8410.
Stable, reactive, and orthogonal tetrazines: dispersion forces promote the cycloaddition with isonitriles. Tu J, Svatunek D, Parvez S, Liu AC, Levandowski BJ, Eckvahl HJ, Peterson RT, Houk KN, Franzini RM. Angew Chem Int Ed Engl. 2019 Jul;58(27):9043.