Theory of Diels-Alder Reactions of Tetrazines

Seminar series
Physical Chemistry Seminar
When
Thu, May 22 12:00pm
Where
2033 Young Hall
Speaker Fang (Acia) Liu
University of California, Los Angeles
Dept. of Chemistry and Biochemistry
Description

Abstract: Diels-Alder reactions of tetrazines have received intense attention for their value in bioorthogonal chemistry since the initial report of their successful application to live cell imaging in 2008. In these pioneering studies, strained alkenes such as trans-cyclooctene and norbornene undergo rapid Diels-Alder cycloaddition reactions with tetrazines as dienophiles. Later, cyclopropenes and cyclooctynes were explored as dienophiles with tetrazines, adding an extra dimension to strain-promoted, or as we have identified, distortion-promoted, cycloadditions in bioorthogonal chemistry. We have undertaken a comprehensive investigation of the substituent and strain effects on the rates of the inverse-electron-demand Diels-Alder reactions of substituted tetrazines with a variety of alkenes and alkynes using density functional theory. We provide a detailed analysis of the factors controlling reactivity for these molecules and predictions of rate constants for as-yet unexplored reactant partners, with an eye toward providing guidance to experimentalists about the most promising reactants for bioorthogonal chemistry and other applications.

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