A highly selective and sensitive endoplasmic reticulum-targeted probe reveals HOCl- and cisplatin-induced HS biogenesis in live cells.

Reactive oxygen species (ROS) and reactive sulfur species (RSS) are involved in many physiological processes and act as collaborators with crosstalk. As an important member of gasotransmitters and RSS, hydrogen sulfide (HS) carries out signaling functions at submicromolar levels because of its high reactivity. Mechanisms of dynamic regulation of ROS and HS production are poorly understood, and the development of a highly selective and organelle-targeted chemical tool will advance the further understanding of HS chemical biology and ROS/RSS crosstalk.

Ligand-Directed H S Probe and Scavenger for Specific Tumor Imaging.

An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H S) might potentially benefit both tumor diagnosis and treatment, but there is still a lack of cancer-targeted molecular tools for in vivo applications. Here, we report the first ligand-directed H S-specific near-infrared fluorescent sensor PSMA-Cy7-NBD and scavenger PSMA-Py-NBD that target the prostate-specific membrane antigen (PSMA). PSMA-Cy7-NBD displays a 53-fold off-on fluorescence response to H S at 803 nm with high specificity.

Insights into self-degradation of cysteine esters and amides under physiological conditions yield new cleavable chemistry.

An unprecedented HS release from cysteine esters and amides (CysO/NHR) under physiological conditions was discovered and the plausible mechanism was proposed. Alkylation of the amino moiety of cysteine esters enables the HS release to be tuned and further provides support to the mechanistic insights. This discovery not only provides new insights into several fundamental science issues including non-enzymatic HS-produced pathways, but also inspires new tunable cleavable motifs for sustained release of arylthiols and even for prodrug design.

A unique reaction of diphenylcyclopropenone and 1,2-aminothiol with the release of thiol for multiple bioconjugation.

Selective reaction of diphenylcyclopropenone (DPCP) and 1,2-aminothiol in water at pH 7.4 produces an amide conjugate with the release of thiol. In addition, structural modifications of DPCP enable the coupling rate to be tuned with a reaction constant of +3.

Rational design of a dual-reactive probe for imaging the biogenesis of both HS and GSH from l-Cys rather than d-Cys in live cells.

Biothiols and their interconversion are involved in cellular redox homeostasis as well as many physiological processes. Here, a dual-reactive dual-quenching fluorescent probe was rationally developed based on thiolysis reactions of 7-nitrobenzoxadiazole (NBD) tertiary amine and 7-cyanobenzoxadiazole (CBD) arylether for imaging of the biothiol interconversion. We demonstrate that the NBD-CBD probe exhibits very weak background fluorescence due to the dual-quenching effects, and can be dual-activated by HS and GSH with an over 500-fold fluorescence increase at 525 nm.

An NBD tertiary amine is a fluorescent quencher and/or a weak green-light fluorophore in HS-specific probes.

The thiolysis of NBD piperazinyl amine (NBD-PZ) is highly selective for HS over GSH and has been widely used for the development of many HS fluorescent probes. Whether the NBD amine in HS-specific probes could be a fluorescent quencher should be further clarified, because NBD amines have been used as environment-sensitive fluorophores for many years. Here, we compared the properties of NBD-based secondary and tertiary amines under the same conditions.

Cell-Trappable BODIPY-NBD Dyad for Imaging of Basal and Stress-Induced HS in Live Biosystems.

HS is a gaseous signaling molecule that is involved in many physiological and pathological processes. In general, the level of intracellular HS (<1 μM) is much lower than that of GSH (∼1-10 mM), leading to the remaining challenge of selective detection and differentiation of endogenous HS in live biosystems. To this end, we quantitatively demonstrate that the thiolysis of NBD amine has much higher selectivity for HS over GSH than that of the reduction of aryl azide.

Thiolysis of CBD arylethers for development of highly GSH-selective fluorescent probes.

Thiolysis of 7-cyanobenzoxadiazole (CBD) arylether was investigated for development of GSH-selective fluorescent probes for the first time. The results demonstrate that CBD-based probes have tunable reactivities and appropriate dissociation constants for GSH, and are highly GSH-selective and suitable for bioimaging.

Investigation of thiolysis of 4-substituted SBD derivatives and rational design of a GSH-selective fluorescent probe.

In order to evaluate 7-sulfonamide benzoxadiazole (SBD) derivatives for the development of fluorescent probes, herein we investigated the thiolysis reactivity and selectivity of a series of SBD compounds with different atoms (N/O/S/Se) at the 4-position. Both SBD-amine and SBD-ether are stable toward biothiols in buffer (pH 7.4), while SBD-selenoether can react efficiently with biothiols GSH/Hcy, Cys, and H2S to produce SBD-SG/S-Hcy, SBD-NH-Cys, and SBD-SH, respectively, with three different sets of spectral signals.

Highly efficient HS scavengers thiolysis of positively-charged NBD amines.

HS is a well-known toxic gas and also a gaseous signaling molecule involved in many biological processes. Advanced chemical tools that can regulate HS levels are useful for understanding HS biology as well as its potential therapeutic effects. To this end, we have developed a series of 7-nitro-1,2,3-benzoxadiazole (NBD) amines as potential HS scavengers.

A H S-Specific Ultrasensitive Fluorogenic Probe Reveals TMV-Induced H S Production to Limit Virus Replication.

Understanding the role of H S in host defense mechanisms against RNA viruses may provide opportunities for the development of antivirals to combat viral infections. Here, we have developed a green-emitting fluorogenic probe, which exhibits a large fluorescence response at 520 nm (>560-fold) when treated with 100 μM H S for 1 h. It is highly selective for H S over biothiols (>400-fold F/F ) and has a detection limit of 12.