Organic Letters
Letter
ACKNOWLEDGMENTS
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This work was supported by the National Institute of Health
(R01GM125968). This work was also supported in part by funds
provided for medical and biological research by the State of
Washington Initiative Measure No. 171.
REFERENCES
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Figure 2. Time-dependent H2S release profiles of 1−3 (200 μM) in the
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release from all of these compounds was observed. Compound 1
exhibited the strongest H2S release with both cysteine and GSH,
which correlated well with its strong reactivity toward both BuSH
and BuNH2. Compounds 2 and 3 showed much slower and
weaker H2S release, which could also be attributed to their
decreased reactivity toward amines and thiols. We also verified
the H2S production of 2/3 (in the presence of cysteine and
GSH) using the H2S gas trapping experiments (Figure S3).
Overall these results suggest cyclic acyl disulfides such as 1 can be
effective thiol-triggered H2S donors while benzene-fused cyclic
acyl disulfides or selenylsulfides such as 2/3 are very weak
donors. The slow or weak release of H2S from 2 and 3 could be
useful for some biological applications when such release profiles
are needed.
In summary, we studied the reactions of three model
compounds (1−3) of cyclic acyl disulfides and cyclic acyl
selenylsulfides. These compounds were found to be effective
precursors for persulfides (RSSH) and selenylsulfides (RSeSH)
upon reacting with nucleophilic species. They could also act as
H2S donors when interacting with cellular thiols. The most
interesting discovery was the generation of RSeSH from
compound 3 under mild conditions. Selenylsulfides (RSeSH)
are expected to be important regulating molecules involved in
Sec-related redox signaling. The method of producing RSeSH
under mild conditions should allow researchers to better
understand the chemical biology of RSeSH. The studies of
other acyl selenylsulfide substrates are currently ongoing in our
laboratory.
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ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge on the
Experimental and characterization of each compound
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AUTHOR INFORMATION
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Corresponding Author
ORCID
(11) Nagel, Z. D.; Klinman, J. P. Chem. Rev. 2006, 106, 3095−3118.
Notes
The authors declare no competing financial interest.
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Org. Lett. XXXX, XXX, XXX−XXX