Photofunctional Cyclometalated Iridium(III) Polypyridine Methylsulfone Complexes as Sulfhydryl-Specific Reagents for Bioconjugation, Bioimaging, and Photocytotoxic Applications

Heteroaromatic methylsulfones have emerged as a new class of electrophiles for selective cysteine modification of peptides and proteins through the formation of a heteroaryl–thiol linkage. The new bioconjugation technique is anticipated provide novel biological reagents for various diagnostic and therapeutic applications. Thus, the introduction of heteroaromatic sulfone groups into iridium(III) complexes is expected to generate new biological reagents for bioconjugation, bioimaging, and photocytotoxic applications. In this work, a series of luminescent iridium(III) heteroaromatic sulfone complexes was designed, synthesized, and characterized. Upon photoexcitation, all the complexes displayed intense and long-lived deep-red emission in solutions and in low-temperature alcohol glass. One of the heteroaromatic sulfone complexes was selected to conjugate with L-cysteine and cysteine-containing peptides or proteins to afford conjugates. The resultant conjugates displayed interesting photophysical and photochemical properties, cellular uptake, localization properties, and (photo)cytotoxic activity. Importantly, all the conjugates showed higher cellular uptake and (photo)cytotoxicity toward cancer cells than normal cells.