Heteroaromatic methylsulfones have emerged as a new class of electrophiles for selective sulfhydryl modification via the formation of a heteroaryl–thiol linkage in proteins. In this work, we designed a new class of iridium(III) methylsulfone complexes for the labeling of cysteine-containing peptides and proteins. Upon photoexcitation, all the complexes exhibited moderately intense NIR emission in solutions and in low-temperature alcohol glass. One of the 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.

We thank the Hong Kong Research Grants Council (Project No. CityU 11300019, CityU 11302820, CityU 11301121, T42-103/16-N, C7075-21GF and N_CityU104/21) for financial support.

Reference

Huang, L.; Leung, P. K.-K.; Lee, L. C.-C.; Guang, X.-X.; Lam, Y.-W.; Lo, K. K.-W. Chem. Commun. 2022, DOI: 10.1039/d2cc02405e.