Bioorthogonal Phosphorogenic Rhenium(I) Polypyridine Sydnone Complexes for Specific Lysosome Labeling

Many novel bioorthogonal reactions have been developed for labeling, such as the strain-promoted sydnone-alkyne cycloaddition (SPSAC), but sydnone-based probes with phosphorogenicity (i. e., phosphorescence turn-on upon reaction) have not been investigated to date. Herein, we report the synthesis, characterization, and photophysical properties of rhenium(I) polypyridine complexes containing a sydnone moiety as bioorthogonal phosphorogenic probes. Their reactions with strained alkyne derivatives and the associated photophysical changes were examined. Upon SPSAC with bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH), the complexes exhibited emission enhancement in the range of 8.8 to 17.3. Importantly, conjugation of the complexes with BCN-modified bovine serum albumin (BCN-BSA) led to the increase in emission enhancement to as high as 38.9 and extended lifetimes in the range of 1.80 to 4.71 μs. Additionally, the bioorthogonal ligation of one of the complexes with a morpholine derivative was shown to induce specific lysosomal labeling in live cells; colocalization studies with LysoTracker Deep Red indicated a Pearson's coefficient of 0.83.