Mitochondrial Specific H₂S_n Fluorogenic Probe for Live Cell Imaging by Rational Utilization of a Dual-Functional-Photocage Group

Abstract

Reactive sulfur species play a very important role in modulating neural signal transmission. Hydrogen polysulfides (H 2 S n , n > 1) are recently suggested to be the actual signaling molecules. There are still few spatiotemporal controllable-based probes to detect H 2 S n . In this work, for the first time, we proposed the photocleavage product of the common photoremovable protecting group (2-nitrophenyl moiety) capable of trapping H 2 S n . Taking advantage of this, we constructed the probe H1 containing a photocontrollable group, a mitochondrial directing unit and a signal reporter fluorescein dye. H1 exhibited excellent fluorescence enhancement (50-fold) in response to H 2 S n under the aqueous buffer only after UV irradiation. H1 also showed high selectivity and sensitivity for H 2 S n over other reactive sulfur species, reactive oxygen species, and other analytes, especially biothoils including hydrogen sulfide, cysteine, homocysteine, and glutathione. We showed the utility of H1 to image H 2 S n in living cells with high spatiotemporal resolution.

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“…Hence, discovery of potent multifunctional/“all-in-one” dyes, with lower tissue autofluorescence, light scattering and photon attenuation, is noteworthy in future photo based therapy (PTT, PDT, PA, etc.). Nowadays, various Janus-faced molecules in disease models have been discovered and their fluorogenic reactions are under development [ [81] , [82] , [83] ]. It is necessary to further enlarge trigger-tool boxes with high sensitivity and selectivity to stimulate future drug discovery.…”

“…Nowadays, various Janus-faced molecules in disease models have been discovered and their fluorogenic reactions are under development [ [81] , [82] , [83] ]. It is necessary to further enlarge trigger-tool boxes with high sensitivity and selectivity to stimulate future drug discovery.…”

Recent advances in probe design to detect reactive sulfur species and in the chemical reactions employed for fluorescence switching

“…Fluorescent probe for persulfide and polysulfide using an aldehyde group. Han et al (35) have reported a photoactivatable and mitochondria-targeting fluorescent probe for hydrogen polysulfides, H1, utilizing an aldehyde group as the reaction site (Fig. 4F).…”

Novel Applications of Lead Acetate and Flow Cytometry Methods for Detection of Sulfur-Containing Molecules

“…Hydrogenous polysulfides are actual signaling molecules with even higher nucleophilicity and reducibility than H 2 S [26]. The fluorescence probes for hydrogenous polysulfides achieved widespread applicability in recent studies [27,28,29,30,31].…”

“…The fluorescence probes for hydrogenous polysulfides achieved widespread applicability in recent studies [27,28,29,30,31]. Some of these probes are even organelle-specific and thus able to selectively label and allow tracing sulfur compounds in mitochondria [26,32]. Moreover, it is possible to monitor, in real-time, variations in polysulfide cell content and/or in vivo [33].…”