Abstract
The isocyano group is the structurally most compact bioorthogonal group known. It
reacts with tetrazines under physiological conditions and has great potential for
widespread use in the biosciences. In this account, we highlight the unique properties
of the isocyano group as a bioorthogonal functionality. Protecting group chemistry
based on the reaction of isonitriles and tetrazines that allows releasing payloads
is a particular focus of the article. We further discuss the atypical steric attractions
that take place in the transition state of the reaction between isonitriles and tetrazines,
which result in an increase in the rate of the reaction with steric bulk of the tetrazine
substituents. These findings will open up new possibilities in bioorthogonal chemistry
where reactivity and stability are simultaneously desired.
1 Introduction
2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry
3 Bioorthogonal Protecting Group Chemistry
4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles
and Tetrazines
5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living
Organisms
6 Conclusions
Key words
bioorthogonal chemistry - isocyanides - protecting groups - steric attraction - cycloadditions
