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Abstract Polymeric donors of gasotransmitters, gaseous signaling molecules such as hydrogen sulfide, nitric oxide, and carbon monoxide, hold potential for localized and extended delivery of these reactive gases. Examples of gasotransmitter donors based on polysaccharides are limited despite the availability and generally low toxicity of this broad class of polymers. In this work, we sought to create a polysaccharide H2S donor by covalently attachingN‐thiocarboxyanhydrides (NTAs) to amylopectin, the major component of starch. To accomplish this, we added an allyl group to an NTA, which can spontaneously hydrolyze to release carbonyl sulfide and ultimately H2S via the ubiquitous enzyme carbonic anhydrase, and then coupled it to thiol‐functionalized amylopectin of three different molecular weights (MWs) through thiol‐ene “click” photochemistry. We also varied the degree of substitution (DS) of the NTA along the amylopectin backbone. H2S release studies on the six samples, termed amyl‐NTAs, with variable MWs (three) and DS values (two), revealed that lower MW and higher DS led to faster release. Finally, dynamic light scattering experiments suggested that aggregation increased with MW, which may also have affected H2S release rates. Collectively, these studies present a new synthetic method to produce polysaccharide H2S donors for applications in the biomedical field.
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Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome
Abstract Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG‐HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG‐OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S to polysulfides and S2O32−in a dose‐dependent manner. The reaction is dependent on O2and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2S exemplified by DS.
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- Award ID(s):
- 2012106
- PAR ID:
- 10441930
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 36
- Issue:
- 10
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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