Hydrogen sulfide (HS) is an important biomolecule, and responsive chemical tools for its delivery are needed. Here, we utilize the photocleavable o-nitrobenzyl group to unmask caged thiocarbamates and to access photoactivated HS releasing molecules. These donors function by the initial release of carbonyl sulfide (COS), which is quickly hydrolyzed to HS by carbonic anhydrase (CA). Our investigations demonstrate that o-nitrobenzyl-caged thiocarbamates can serve as a donor platform for the bio-orthogonal stimulated release of COS/HS.
Fluorophores are powerful tools for interrogating biological systems. Carbon nanotubes (CNTs) have long been attractive materials for biological imaging due to their nearinfrared excitation and bright, tunable optical properties. The difficulty in synthesizing and functionalizing these materials with precision, however, has hampered progress in this area. Carbon nanohoops, which are macrocyclic CNT substructures, are carbon nanostructures that possess ideal photophysical characteristics of nanomaterials, while maintaining the precise synthesis of small molecules. However, much work remains to advance the nanohoop class of fluorophores as biological imaging agents. Herein, we report an intracellular targeted nanohoop. This fluorescent nanostructure is noncytotoxic at concentrations up to 50 μM, and cellular uptake investigations indicate internalization through endocytic pathways. Additionally, we employ this nanohoop for two-photon fluorescence imaging, demonstrating a high two-photon absorption cross-section (65 GM) and photostability comparable to a commercial probe. This work further motivates continued investigations into carbon nanohoop photophysics and their biological imaging applications.
H2S is a well-known toxic gas and also a gaseous signaling molecule involved in many biological processes. Advanced chemical tools that can regulate H2S levels in vivo are useful for...
Investigations into hydrogen sulfide (H 2 S) signaling pathways have demonstrated both the generation and importance of persulfides, which are reactive sulfur species that contain both reduced and oxidized sulfur. These observations have led researchers to suggest that oxidized sulfur species, including sulfane sulfur (S 0), are responsible for many of the physiological phenomena initially attributed to H 2 S. A common method of introducing S 0 to biological systems is the administration of organic polysulfides, such as diallyl trisulfide (DATS). However, prior reports have demonstrated that commercially-available DATS often contains a mixture of polysulfides, and furthermore a lack of structure-activity relationships for organic polysulfides has limited our overall understanding of different polysulfides and their function in biological systems. Advancing our interests in the chemical biology of reactive sulfur species including H 2 S and S 0 , we report our investigations into the rates and quantities of H 2 S release from a series of synthetic, pure benzyl polysulfides, ranging from monosulfide to tetrasulfide. We demonstrate that H 2 S is only released from the trisulfide and tetrasulfide, and that this release requires thiol-mediated reduction in the presence of cysteine or reduced glutathione. Additionally, we demonstrate the different effects of trisulfides and tetrasulfides on cell proliferation in murine epithelial bEnd.3 cells.
Hydrogen selenide (H 2 Se) is a central metabolite in the biological processing of selenium for incorporation into selenoproteins, which play crucial antioxidant roles in biological systems. Despite being integral to proper physiological function, this reactive selenium species (RSeS) has received limited attention. We recently reported an early example of a H 2 Se donor (TDN1042) that exhibited slow, sustained release through hydrolysis. Here we expand that technology based on the PSe motif to develop cyclic-PSe compounds with increased rates of hydrolysis and function through well-defined mechanisms as monitored by 31 P and 77 Se NMR spectroscopy. In addition, we report a colorimetric method based on the reaction of H 2 Se with NBD-Cl to generate NBD-SeH (λ max = 551 nm), which can be used to detect free H 2 Se. Furthermore, we use TOF-SIMS (time of flight secondary ion mass spectroscopy) to demonstrate that these H 2 Se donors are cell permeable and use this technique for spatial mapping of the intracellular Se content after H 2 Se delivery. Moreover, these H 2 Se donors reduce endogenous intracellular reactive oxygen species (ROS) levels. Taken together, this work expands the toolbox of H 2 Se donor technology and sets the stage for future work focused on the biological activity and beneficial applications of H 2 Se and related bioinorganic RSeS.
Sulfane sulfur, or S0, is found in polysulfide and persulfide compounds in biology. We demonstrate that modified cyclodextrins can solubilize S8 in water, increase its reactivity with biological nucleophiles, and enable delivery to live cells.
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