Iridium(III) bis-Nitrone Complexes as Innovative Phosphorogenic Reagents for Bioimaging and Phototherapeutics

Nitrones are a relatively new bioorthogonal system that show high reactivity toward strained cyclooctynes via the strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction. Transition metal complexes containing a nitrone moiety are weakly emissive but exhibit intense and long-lived emission upon reaction with strained alkynes such as (1R,8S,9s)-bicyclo[6.1.0]nonyne (BCN).1 In this work, cyclometalated iridium(III) complexes functionalized with two nitrone units have been designed as novel phosphorogenic bioorthogonal reagents for bioimaging and phototherapy. Upon reaction with BCN substrates, the reaction mixture displayed significant emission enhancement and lifetime extension. Importantly, the complexes showed a higher reaction rate toward a bis-cyclooctyne derivative (bis-BCN) compared with its monomeric counterpart. Additionally, the cellular uptake, imaging and photocytotoxic properties of the complexes were explored. The crosslinking properties of the complexes mean that they are potential candidates for the construction of polymeric materials and stapled peptides.