I Bind It That Way – Bioorthogonal Unmasking of Pro‐Fluorescent Quinone Methides

Abstract

AbstractProof‐of‐concept studies for the bioorthogonally controlled generation of pro‐fluorescent quinone‐methides are presented here. The novel concept relies on a click‐to‐release tetrazine unit that chemically cages a pro‐fluorescent quinone methide precursor. On a synthetically readily accessible model compound we demonstrate that IEDDA reaction of the tetrazine with a TCO leads to the liberation of a pro‐fluorescent quinone methide, which is readily captured by nearby nucleophiles to form a fluorescent scaffold. Unlike in previous approaches to access bioorthogonally activatable fluorogenic probes, where the tetrazine unit acted as a quencher of fluorescence, the role of the tetrazine is redefined here. Such repurposed role of tetrazines is foreseen to address the limitations of tetrazine‐quenched red/NIR excitable fluorogenic probes.