title: Mechanism-Based Fluorogenic trans-Cyclooctene-Tetrazine Cycloaddition.
abstract: The development of fluorogenic reactions which lead to the formation of fluorescent products from two nonfluorescent starting materials is highly desirable, but challenging. Reported herein is a new concept of fluorescent product formation upon the inverse electron-demand Diels-Alder reaction of 1,2,4,5-tetrazines with particular trans-cyclooctene (TCO) isomers. In sharp contrast to known fluorogenic reagents the presented chemistry leads to the rapid formation of unprecedented fluorescent 1,4-dihydropyridazines so that the fluorophore is built directly upon the chemical reaction. Attachment of an extra fluorophore moiety is therefore not needed. The photochemical properties of the resulting dyes can be easily tuned by changing the substitution pattern of the starting 1,2,4,5-tetrazine. We support the claim with NMR measurements and rationalize the data by computational study. Cell-labeling experiments were performed to demonstrate the potential of the fluorogenic reaction for bioimaging.
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Arcadio
authors.initials: A
authors.lastname: Vázquez
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Dzijak
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Rampmaier
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Siegl
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Milan
authors.identifier: 0000-0001-6633-4351
authors.initials: M
authors.lastname: Vrabel
keywords: bioorthogonal chemistry; click reactions; cycloaddition; heterocycles; imaging agents