Design, Synthesis And Spectra Study Of Gasotransmitter H₂S Fluorescent Probes

For centuries, hydrogen sulfide (H2S) has been viewed primarily as a noxious chemical species that is naturally produced by geological and microbial activities. H2S is a colorless, flammable gas, which gives rotten eggs distinctive odor, can trigger eye and respiratory tract irritation. Inhalation of excess H2S can result in loss of consciousness, respiratory failure, cardiacarrest, and, in extreme cases, death.However, more recent studies have shown that mammals can also produce H2S in a controlled fashion to maintain normal physiology. Edogenous H2S contributes to physiology and pathology in regulating nervous system, cardiovascular system, endocrine system, immune system and digestive system, and have been regarded as the third gaseous transmitter besides nitric oxide (NO) and carbon monoxide (CO). Therefore, in-depth study of endogenous H2S is of great importance.Fluorescence-based assays possess unique superiorities in the study of the cellular signal transduction, physiological and pathological functions, and have found widespread application in detection of reactive species in vivo due to its high selectivity and sensitivity, nondestructive detection, and in-situ real time analysis. Now, how to design efficient fluorescent probes for rapid, accurate, convenient and sensitive detection of H2S in biological systems is becoming a research focus in the field of molecular recognition and sense.Although many H2S fluorescent probes have been reported based on several significant characteristic properties of H2S, there still exist some issues of interest and concern. One is how to avoid the probe consumption by biothiols, and the other is how to develop sensitive fluorescent probes that could exhibit obvious signal change to low concentration of H2S.In response to the first problem, taking advantage of dual nucleophilicity of H2S and its relatively low pKa values compared with biothiols Cys、Hcy、 GSH, we present a fluorescent probe 2-1 for detection of H2S in aqueous solution through integration of a new H2S trap group 2-(iodomethyl)benzoate and a potential fluorescent reporter methylf-luorescein. The H2S-induced substitution-cyclization cascade reaction would release the ring-opening methylfluorescein, thereby leading to the fluorescence "off-on" response, we examined the reactivity of fluorescent probe 2-1 to H2S by fluorescence emission spectrum, and the results show that the probe can highly selectively detect H2S even in the presence of millimolar concentrations of biothiols and consumption by biothiols was not observed.In response to the second problem, we present a simple and new fluorescent probe 3-1 for the detection of H2S based on the reduction of an azido group by H2S as well as the resulting ESIPT modulated fluorescence off-on response. The probe can highly selectively detect H2S even in the presence of anions, cations, biothiols, and sodium ascorbate, and highly sensitively respond to low concentration of H2S, possessing extremely low detection limit of 0.78 nm, which, as far as we know, is the most sensitive fluorescent probe for H2S to date. Preliminary fluorescence imaging experiments in cells indicate its potential to probe H2S chemistry in biolo-gical systems.