Stable, Reactive, and Orthogonal Tetrazines: Dispersion Forces Promote the Cycloaddition with Isonitriles.
Angew Chem Int Ed Engl
; 58(27): 9043-9048, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31062496
ABSTRACT
The isocyano group is a structurally compact bioorthogonal functional group that reacts with tetrazines under physiological conditions. Now it is shown that bulky tetrazine substituents accelerate this cycloaddition. Computational studies suggest that dispersion forces between the isocyano group and the tetrazine substituents in the transition state contribute to the atypical structure-activity relationship. Stable asymmetric tetrazines that react with isonitriles at rate constants as high as 57â
L mol-1 s-1 were accessible by combining bulky and electron-withdrawing substituents. Sterically encumbered tetrazines react selectively with isonitriles in the presence of strained alkenes/alkynes, which allows for the orthogonal labeling of three proteins. The established principles will open new opportunities for developing tetrazine reactants with improved characteristics for diverse labeling and release applications with isonitriles.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetrazóis
/
Nitrilas
Limite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY