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A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential
Author(s) -
Powell Chadwick R.,
Dillon Kearsley M.,
Wang Yin,
Carrazzone Ryan J.,
Matson John B.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803087
Subject(s) - chemistry , reactive oxygen species , reactivity (psychology) , cysteine , redox , nucleophile , sulfur , oxygen , oxidative phosphorylation , sodium sulfide , hydrogen sulfide , reducing agent , reactive intermediate , combinatorial chemistry , stereochemistry , biochemistry , catalysis , enzyme , organic chemistry , medicine , alternative medicine , pathology
Persulfides (RSSH) have been hypothesized as critical components in sulfur‐mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H 2 S). Hindering the study of persulfides is a lack of persulfide‐donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS‐responsive (ROS=reactive oxygen species), self‐immolative persulfide donor. The donor, termed BDP‐NAC, showed selectivity towards H 2 O 2 over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N ‐acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H 2 O 2 revealed that BDP‐NAC mitigated the effects of a highly oxidative environment in a dose‐dependent manner over relevant controls and to a greater degree than common H 2 S donors sodium sulfide (Na 2 S) and GYY4137. BDP‐NAC also rescued cells more effectively than a non‐persulfide‐releasing control compound in concert with common H 2 S donors and thiols.