Click to Release: Instantaneous Doxorubicin Elimination upon Tetrazine Ligation

<p>Eliminated without a trace: The fastest click reaction, the highly selective inverse-electron-demand Diels-Alder reaction, has been modified to enable selective bioorthogonal release. Thus, the click reaction of a tetrazine with a drug-bound trans-cyclooctene caused the instantaneous release of the drug and CO₂ (see scheme). One possible application is the chemically triggered release, and thereby activation, of a drug from a tumor-bound antibody-drug conjugate.</p>