Spatiotemporally controllable nitric oxide (NO)-releasers allow us to analyze the physiological effects of NO, a gaseous mediator that modulates many biological signaling networks, and are also candidate chemotherapeutic agents. We designed and synthesized a blue-light-controllable NO releaser, named NOBL-1, which bears an N-nitrosoaminophenol moiety for NO release tethered to a BODIPY dye moiety for harvesting blue light. Photoinduced electron transfer from N-nitrosoaniline to the antenna moiety upon irradiation with relatively noncytotoxic blue light (470-500 nm) should result in NO release with formation of a stable quinone moiety. NO release from NOBL-1 was confirmed by ESR spin trapping and fluorescence detection. Spatially controlled NO release in cells was observed with DAR-4M AM, a fluorogenic NO probe. We also demonstrated temporally controlled vasodilation of rat aorta ex vivo by blue-light-induced NO release from NOBL-1. This compound should be useful for precise examination of the functions of NO with excellent spatiotemporal control.

Nitroxyl (HNO) is a one-electron reduced and protonated derivative of nitric oxide (NO) and has characteristic biological and pharmacological effects distinct from those of NO. However, studies of its biosynthesis and activities are restricted by the lack of versatile HNO detection methods applicable to living cells. Here, we report the first metal-free and reductant-resistant HNO imaging probe available for use in living cells, P-Rhod. It consists of a rhodol derivative moiety as the fluorophore, linked via an ester moiety to a diphenylphosphinobenzoyl group, which forms an aza-ylide upon reaction with HNO. Intramolecular attack of the aza-ylide on the ester carbonyl group releases a fluorescent rhodol derivative. P-Rhod showed high selectivity for HNO in the presence of various biologically relevant reductants, such as glutathione and ascorbate, in comparison with previous HNO probes. We show that P-Rhod can detect not only HNO enzymatically generated in the horseradish peroxidase-hydroxylamine system in vitro but also intracellular HNO release from Angeli's salt in living cells. These results suggest that P-Rhod is suitable for detection of HNO in living cells.

We report the design, synthesis and application of a directly photocontrollable hydrogen sulfide (H2S) donor, which releases H2S proportionally to the intensity and duration of photoirradiation. Photocontrolled H2S release from this donor was also demonstrated in bovine serum. This H2S donor should be suitable for use in various biological systems.

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Nitric oxide (NO) has been known as a gaseous chemical mediator, which modulates several physiological functions. Spatial and temporal control of NO release facilitates further study and medical application of NO. Herein, we report design and synthesis of a novel NO donor, NO-Rosa. NO-Rosa has a rosamine moiety, which absorbs yellowish green light. Upon irradiation with yellowish green light (530-590 nm), NO is released from NO-Rosa, presumably via photoinduced electron transfer from the N-nitrosoaminophenol moiety to the rosamine moiety. NO release from NO-Rosa was detected by ESR spin trapping and a NO fluorescent probe. Cellular NO release control was achieved in HEK293 cells using a NO fluorescent probe, DAF-FM DA. Furthermore, temporally controlled NO-induced vasodilation was demonstrated by treatment of a rat aortic strip with NO-Rosaex vivo and irradiation by yellowish green light. NO-Rosa is expected to be utilized for further study of NO-related physiological functions, utilizing its ability of spatiotemporal release of NO as a photocontrollable compound with harmless yellowish-green light.