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

Abstract

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.

Multicharged cyclodextrin supramolecular assemblies

“…The inner cavity is typically used to encapsulate size-matched guest molecules to form complexes through host-guest interactions. [55][56][57][58][59] Because of the differences in the number of D-glucose units in a-, b-, and g-CDs, the minimum internal diameter on the primary side, the maximum internal diameter on the secondary side, and the cavity volume are also different (Fig. 1b), meaning that guest molecules of different sizes can be encapsulated into the three hosts.…”

Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking

“…As expected, we observed a significant increase in the S 8 absorbance for solutions of CB[7], whereas significant increases in S 8 absorbances were not observed for CB[6] or CB[8] (Figure S3). Using this method, we could readily solubilize 1.0 ± 0.3 mM S 8 in 20 mM solutions of CB[7], which is significantly more efficient than the 2 mM solubility of S 8 in 50% w/w (∼360 mM) solutions of 2HPβ from prior work …”

“…In more recent work, we recently showed that the fully organic 2-hydroxypropyl β-cyclodextrin (2HPβ) could also be used to solubilize S 8 in water. Using a 50 wt % solution of 2HPβ resulted in up to 2 mM S 8 in water, and the resultant 2HPβ/S 8 complex could be used to decrease NO 2 – production in Raw 264.7 macrophage cells stimulated with proinflammatory lipopolysaccharides . Similarly, treatment of isolated GAPDH enzyme with 2HPβ/S 8 modulates enzyme activity through sulfuration of a key GAPDH Cys residue .…”

An NBD tertiary amine is a fluorescent quencher and/or a weak green-light fluorophore in H2S-specific probes

“…2 Biological H 2 S has been demonstrated to have roles in the regulation of angiogenesis, vasodilation, metabolic bioenergetics, immune response, oxidative stress, inflammatory processes, etc. 3 Recent studies suggest that H 2 S could play important roles in microbial pathogenesis including the anti-viral effect for COVID-19. 4 In addition, the endogenous level of H 2 S may be useful as an index to diagnose diseases 5 and even to evaluate the therapeutic effect of some diseases including cancer and asthma.…”