A Rhenium(I) Polypyridine Tetrazine Complex as Phosphorogenic Bioorthogonal Reagent for Release of Functional Payloads

There has been growing interest in developing bioorthogonal cleavage reactions for targeted delivery of functional payloads, such as fluorophores and drugs, in living systems. The bioorthogonal chemistry of tetrazines and isonitriles has gained attention due to the structural compactness of the isonitrile group that minimizes perturbation to biological environments.1 Based on our interest in photofunctional transition metal complexes as bioimaging reagents and photosensitizers for photodynamic therapy, a rhenium(I) polypyridine complex functionalized with a tetrazylmethyl group (1) was designed as a novel bioorthogonal turn-on reagent for triggering and monitoring the release of payloads. Upon reaction with an isonitrile derivative, the complex displayed substantial emission enhancement and lifetime extension. The reaction was monitored by HPLC analysis and showed near-quantitative release of the tetrazylmethyl-free complex. The high photoinduced singlet oxygen generation efficiency of the complex demonstrated its potential as a phototherapeutic reagent.