Svatunek, D., Denk, C., & Mikula, H. (2018). A computational model to predict the Diels–Alder reactivity of aryl/alkyl-substituted tetrazines. Monatshefte Für Chemie - Chemical Monthly. https://doi.org/10.1007/s00706-017-2110-x
The tetrazine ligation is one of the fastest bioorthogonal ligations and plays a pivotal role in time-critical in vitro and in vivo applications. However, prediction of the reactivity of tetrazines in inverse electron demand Diels–Alder-initiated ligation reactions is not straight-forward. Commonly used tools such as frontier molecular orbital theory only give qualitative and often even wrong results. Applying density functional theory, we have been able to develop a simple computational method for the prediction of the reactivity of aryl/alkyl-substituted tetrazines in inverse electron demand Diels–Alder reactions.