The Path to Controlled Delivery of Reactive Sulfur Species

Abstract

Metrics & More Article Recommendations CONSPECTUS: Reactive sulfur species (RSS) play regulatory roles in many physiological and pathological processes. Since the discovery of hydrogen sulfide (H 2 S) as a nitric oxide (NO)-like signaling molecule, understanding the chemical biology of H 2 S and H 2 S-related RSS, such as hydropersulfides (RSSH) and polysulfides (H 2 S n ), has become a fast-growing research field. However, the research on these RSS has technical difficulties due to their high reactivity and instability. To solve this problem, considerable efforts have been put into the development of unique RSS releasing compounds (e.g., donors) or in situ RSS generation systems. This Account tells the story of our research group's effort to develop novel RSS donors.We began with exploring molecular entities that were stable by themselves but could be triggered by biologically relevant factors, such as pH, thiols, light, or enzymes, to release H 2 S in a controllable fashion. These studies led to the discovery of a series of novel H 2 S donors. We later expanded our interests to other RSS including RSSH, H 2 S n , RSeSH, HSNO, RSOH, etc. The fundamental chemistry of these RSS was studied and applied to the development of the corresponding donors. In addition to small molecule donors, we also worked on H 2 S-releasing biomaterials and their applications. This Account summarizes our work and systematically explains how each RSS donor template was proposed and evaluated. The Account covers the following key points: (1) rational chemistry design of each RSS donor template, (2) evaluation and mechanistic insights of each donor template, and (3) properties and biological applications of the donors. ■ KEY REFERENCES• Zhao, Y.; Wang, H.; Xian, M. Cysteine-activated hydrogen sulfide (H 2 S) donors. J. Am. Chem. Soc. 2011, 133, 15−17. 1 The concept of controlled H 2 S donors is formulated for the f irst time.

Progress and perspective on hydrogen sulfide donors and their biomedical applications

“…In this sense, the rapid release property of sulfide salts (NaHS and Na 2 S) would contribute to the inaccurate experimental parameters of drug concentration and duration, which unpremeditatedly gives rise to random and misleading, or even paradoxical, results in the same aspect of certain investigation 13,119,121 . In view of these drawbacks and limitations, considerable impetus was devoted during the past many years to the development of H 2 S donors that release H 2 S sustainably at controllable rates under physiological conditions 117–120 . Lawesson's reagent (LR, donor 1 , Figure 3), originally developed as a sulfurization reagent, 133 had proven to be capable of releasing H 2 S in aqueous solution more slowly than sulfide salts.…”

“…On this ground, H 2 S‐releasing agents (also named H 2 S donors) seem to be adequate for either mimicking the endogenous H 2 S generation under physiological conditions, or replenishing additional H 2 S for both diagnostic and therapeutical purposes. During the past years, substantial endeavor has been made to develop various H 2 S donors, and a number of H 2 S donors with different releasing rates and mechanisms have been reported 101,105–125 . H 2 S donors, regarded as the exogenous suppliers of H 2 S, could be employed as the ideal candidates for the treatment of diseases whose H 2 S‐associated networks might be short‐circuited.…”

A Novel Electrochemically Switchable Conductive Polymer Interface for Controlled Capture and Release of Chemical and Biological Entities

“…As a result, materials and interfaces that can capture, stabilize and release them when required are needed. [ 12 ] Antibodies are another class of biologically important molecules that have been of great interest in controlled delivery systems with applications in antibody purification and antibody‐based therapeutic platforms. [ 13 ] Local and controlled delivery systems can improve the therapeutic effects of antibodies by providing a highly regulated antibody concentration at the targeted body site over time, thus improving their bioavailability and reducing the possible side effects.…”

Optimization of a Method for Detecting Intracellular Sulfane Sulfur Levels and Evaluation of Reagents That Affect the Levels in Escherichia coli

“…The iSS is unstable, as it can be oxidized by oxygen, reduced by thiols, and decomposed under acid conditions [ 14 , 15 ]. Therefore, the growth conditions and oxidative and reducing agents may interfere with iSS in bacteria.…”