Bioorthogonal Control of the Phosphorescence and Singlet Oxygen Photosensitization Properties of Iridium(III) Tetrazine Complexes

Tetrazine is a commonly used bioorthogonal handle that quenches the emission of the appended fluorophores by different mechanisms, including Förster resonance energy transfer (FRET), through-bond energy transfer (TBET), photoinduced electron transfer (PET) and intramolecular charge-transfer (ICT). It undergoes inverse electron-demand Diels–Alder (IEDDA) reaction with dienophiles including strained alkynes and alkenes to give the corresponding pyridazine and dihydropyridazine products, respectively. The rich photophysical properties of iridium(III) polypyridine complexes have been exploited for biomolecular sensing and imaging applications. These complexes usually display long-lived triplet excited states that render them excellent photosensitizers for singlet oxygen (¹O₂). Herein, we report a new class of iridium(III) tetrazine complexes that exhibit very different photophysical and photochemical behavior after reactions with strained dienophile derivatives. Based on the photophysical and photochemical properties in the resulting derivatives, these complexes were utilized for the specific staining of organelles such as lysosomes and endoplasmic reticulum of human cervical carcinoma HeLa cells. Furthermore, in combination with the HaloTag technology, the control of intracellular photocytotoxicity activity of the complexes was demonstrated with different strained dienophile derivatives.