Biological reactive sulfur species (RSS), such as the polysulfides found in garlic, exhibit tissue-protective activity such as anti-inflammation and antioxidation. The signaling molecule hydrogen sulfide (H2S) is produced during polysulfide metabolism and also has well-documented protective effects, along with participating in pathways like angiogenesis. Sulfane sulfur (S0) atoms within these RSS are being studied as potential causative agents for the observed effects of RSS on tissues. Molecules of pure S0 are only found as elemental sulfur, or S8, and are used by some Archaean organisms in deep-sea vent environments as an energy source. Given the poor solubility of S8 (~19 nM), it is unclear how these organisms can access solubilized S8 for biological purposes. Crystallographic structures of the tetrabrachion of Staphylothermus marinus have revealed that this organism encapsulates S8 within some hydrophobic regions of its protein, demonstrating a means of S8 storage for biological use. With this system in mind, we conceived a method of S8 encapsulation and solvation using cyclodextrins: cyclic oligosaccharides with hydrophilic exteriors and hydrophobic cores. We used 2-hydroxypropyl beta-cyclodextrin (2HPb) to solvate S8 up to 2.0 ± 0.2 mM in aqueous solution. Solvated S8 is chemically accessible and is reduced by tris(2-carboxyethyl)phosphine (TCEP). S8 also reacts with biological thiols cysteine and glutathione (GSH) to form H2S in solution. When HeLa cells are incubated with solvated S8, increased levels of intracellular S0 were seen. Raw 264.7 macrophage cells pretreated with solvated S8 demonstrated lower levels of inflammatory NOx compounds after subsequent lipopolysaccharide (LPS) treatment. These results demonstrate a novel and economic means of S0 solvation and delivery to cells via creation of a 2HPb/S8 complex. The solvated S0 serves as an H2S donor and anti-inflammatory agent. This system provides new opportunities for the study of S0 in biological systems, which can be used in the study of RSS.

Modified cyclodextrins solubilize elemental sulfur in water and enable biological sulfane sulfur delivery

ACS Spring Meeting 2021

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