Reactive sulfur species (RSS) are biologically important molecules. Among them, H S, hydrogen polysulfides (H S n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur-related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O-silyl-mercaptan-based sulfur-containing molecules which undergo pH- or F -mediated desilylation to release the corresponding H S, H S , RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH- or F -triggered RSS donors. Moreover, we have demonstrated that the O-silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase-activated donors).

Recent studies suggest that inorganic hydrogen polysulfides (H S , n ≥ 2) play important regulatory roles in redox biology. Modulation of their cellular levels could have potential therapeutic value. This review article focuses on our current understanding of the biosynthesis, biofunctions, fundamental physical/chemical properties, detection methods and delivery techniques of H S .

Reactive sulfur species (RSS) are biologically important molecules. Among them, H2S, hydrogen polysulfides (H2Sn, n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur‐related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O‐silyl‐mercaptan‐based sulfur‐containing molecules which undergo pH‐ or F−‐mediated desilylation to release the corresponding H2S, H2Sn, RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH‐ or F−‐triggered RSS donors. Moreover, we have demonstrated that the O‐silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase‐activated donors).

A convenient method for the preparation of unsymmetrical trisulfides using 9-fluorenylmethyl (Fm) disulfide as the precursors is reported. This method gives the desired trisulfides in good yields under mild conditions.

C-Nitrosothioformamide was demonstrated to be a donor template for dual release of HNO and COS triggered by a retro-Diels-Alder reaction. COS is an H 2 S precursor in the presence of carbonic anhydrase. This process produces HNO and H 2 S in a slow but steady manner. As such, the direct reaction between HNO and H 2 S under this situation appears to be minor. This may provide a useful tool for studying the synergistic effects of HNO and H 2 S.

This cover image is composed of a Tai Chi symbol containing the two significant small molecules H2S and HNO, which are simultaneously produced by the donor molecule contained in the center. H2S and HNO operate within a complex scheme of interdependencies that are not fully understood. Exploration of these interactions termed ‘crosstalk’ are one application of this work. H2S and HNO are small gaseous molecules which are highly mobile, so they are shown speeding away from the donor. More information can be found in the Research Article by M. Xian et al.