Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling.
We report a new class of ruthenium(II) polypyridine complexes functionalized with a nitrone group as phosphorogenic bioorthogonal probes. These complexes were very weakly emissive owing to rapid C=N isomerization of the nitrone moiety, but exhibited significant emission enhancement upon strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction with bicyclo[6.1.0]nonyne (BCN)-modified substrates. The modification of nitrone with a dicationic ruthenium(II) polypyridine unit at the α-C-position and a phenyl ring at the N-position led to remarkably accelerated reaction kinetics, which are substantially greater (up to ≈278 fold) than those of other acyclic nitrone-BCN systems. Interestingly, the complexes achieved specific cell membrane/cytosol staining upon specific labeling of an exogenous substrate, BCN-modified decane (BCN-C10), in live cells. Importantly, the in situ generation of the more lipophilic isoxazoline adduct in the cytoplasm resulted in increased cytotoxicity, highlighting a novel approach to apply the SPANC labeling technique in drug activation.
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P.R. China.
Tommy Siu-Ming
TS
Tang
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P.R. China.
Hua-Wei
HW
Liu
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P.R. China. bhkenlo@cityu.edu.hk.|State Key Laboratory of Millimeter Waves, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P.R. China. bhkenlo@cityu.edu.hk.|Center for Functional Photonics, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P.R. China. bhkenlo@cityu.edu.hk.
Kenneth Kam-Wing
http://orcid.org/0000-0002-2470-5916
KK
Lo
D000480:Alkynes / Q000737:chemistry*; D061565:Cycloaddition Reaction; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D009589:Nitrogen Oxides / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013194:Staining and Labeling
D000480:Alkynes; D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; D009589:Nitrogen Oxides; C015388:nitrones; D012428:Ruthenium
bioorthogonal labeling; imaging agents; nitrone; phosphorogenic; ruthenium