| Autor: |
Mak EC; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China., Chen Z; Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China., Lee LC; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China.; Laboratory for Synthetic Chemistry and Chemical Biology Limited, Units 1503-1511, 15/F, Building 17 W, Hong Kong Science Park, New Territories, Hong Kong, P. R. China., Leung PK; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China.; State Key Laboratory of Terahertz and Millimeter Waves, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China., Yip AM; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China.; Laboratory for Synthetic Chemistry and Chemical Biology Limited, Units 1503-1511, 15/F, Building 17 W, Hong Kong Science Park, New Territories, Hong Kong, P. R. China., Shum J; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China., Yiu SM; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China., Yam VW; Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China., Lo KK; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China.; State Key Laboratory of Terahertz and Millimeter Waves, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China. |
| Abstrakt: |
Cross-linking strategies have found wide applications in chemical biology, enabling the labeling of biomolecules and monitoring of protein-protein interactions. Nitrone exhibits remarkable versatility and applicability in bioorthogonal labeling due to its high reactivity with strained alkynes via the strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction. In this work, four cyclometalated iridium(III) polypyridine complexes functionalized with two nitrone units were designed as novel phosphorogenic bioorthogonal reagents for bioimaging and phototherapeutics. The complexes showed efficient emission quenching, which is attributed to an efficient nonradiative decay pathway via the low-lying T 1 /S 0 minimum energy crossing point (MECP), as revealed by computational studies. However, the complexes displayed significant emission enhancement and lifetime extension upon reaction with (1 R ,8 S ,9 s )-bicyclo[6.1.0]non-4-yne (BCN) derivatives. In particular, they showed a remarkably higher reaction rate toward a bis -cyclooctyne derivative ( bis -BCN) compared with its monomeric counterpart ( mono -BCN). Live-cell imaging and (photo)cytotoxicity studies revealed higher photocytotoxicity in bis -BCN-pretreated cells, which is ascribed to the enhanced singlet oxygen ( 1 O 2 ) photosensitization resulting from the elimination of the nitrone-associated quenching pathway. Importantly, the cross-linking properties and enhanced reactivity of the complexes make them highly promising candidates for the development of hydrogels and stapled/cyclized peptides, offering intriguing photophysical, photochemical, and biological properties. Notably, a nanosized hydrogel ( 2-gel ) demonstrated potential as a drug delivery system, while a stapled peptide ( 2- bis -pDIKK ) exhibited p53-Mdm2 inhibitory activity related to apoptosis and a cyclized peptide ( 2- bis -RGD ) showed cancer selectivity. |
