Bioluminescence Imaging of Carbon Monoxide in Living Cells and Nude Mice Based on Pd-Mediated Tsuji-Trost Reaction.

Carbon monoxide (CO) is highly toxic and lethal to humans and animals because of its strong affinity for hemoglobin, while this "silent killer" is constantly generated in the body as a cell-signaling molecule of the gasotransmitter family in various pathological and physiological conditions. Up to now, designing fluorescent probes for real-time imaging of CO in living species is a continuous challenge due to background interference, light scattering, and photoactivation/photobleaching. Herein, a novel type of bioluminescence probe (allyl-luciferin) was synthesized and exploited to realize CO imaging with high signal-to-noise ratios. Based on Pd-mediated Tsuji-Trost reaction, allyl-luciferin specifically reacted with CO to yield D-luciferin and thus generate a turn-on bioluminescence response, exhibiting high selectivity against bioactive small molecules such as reactive nitrogen, oxygen, and sulfur species. Furthermore, the new probe can be easily employed to detect exogenous CO in Huh7 cells and MDA-MB-231 cells, and CO production was enhanced greatly in these living cells after pretreatment with [Ru(CO)Cl-(glycinate)] (CORM-3). Through the use of PdCl-containing liposomes to improve poor membrane permeability of PdCl, endogenous CO stimulated by heme was also seen clearly. In addition, the probe was successfully used to monitor exogenous and endogenous CO in nude mice. Overall, our data proved that the allyl-luciferin is a promising tool for exogenous and endogenous CO detection and imaging within living species. This is the first demonstration of bioluminescence imaging obtained by a probe for CO. We anticipate that the good imaging properties of allyl-luciferin presented in this study will provide a potentially powerful approach for illuminating CO functions in the future.