The chemical biology of the persulfide (RSSH)/perthiyl (RSS·) redox couple and possible role in biological redox signaling.
The recent finding that hydropersulfides (RSSH) are biologically prevalent in mammalian systems has prompted further investigation of their chemical properties in order to provide a basis for understanding their potential functions, if any. Hydropersulfides have been touted as hyper-reactive thiol-like species that possess increased nucleophilicity and reducing capabilities compared to their thiol counterparts. Herein, using persulfide generating model systems, the ability of RSSH species to act as one-electron reductants has been examined. Not unexpectedly, RSSH is relatively easily oxidized, compared to thiols, by weak oxidants to generate the perthiyl radical (RSS·). Somewhat surprisingly, however, RSS· was found to be stable in the presence of both O2and NO and only appears to dimerize. Thus, the RSSH/RSS· redox couple is readily accessible under biological conditions and since dimerization of RSS· may be a rare event due to low concentrations and/or sequestration within a protein, it is speculated that the general lack of reactivity of individual RSS· species may allow this couple to be utilized as a redox component in biological systems.
Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
Christopher L
CL
Bianco
Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
Tyler A
TA
Chavez
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
Victor
V
Sosa
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
Simran S
SS
Saund
Department of Chemistry, University of California, Davis, One Shield Ave., Davis, CA 95616, United States.
Q Nhu N
QNN
Nguyen
Department of Chemistry, University of California, Davis, One Shield Ave., Davis, CA 95616, United States.
Dean J
DJ
Tantillo
Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132-4163, United States.
Andrew S
AS
Ichimura
Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States. Electronic address: jtoscano@jhu.edu.
John P
JP
Toscano
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States. Electronic address: fukuto@sonoma.edu.
Jon M
JM
Fukuto
D000975:Antioxidants / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry*; D019281:Dimerization; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D015398:Signal Transduction; D012996:Solutions; D013113:Spin Labels; D013440:Sulfides / Q000737:chemistry*; D013816:Thermodynamics
D000975:Antioxidants; D003497:Cyclic N-Oxides; D012996:Solutions; D013113:Spin Labels; D013440:Sulfides; C051552:persulfides; D010100:Oxygen; C001803:tempol
Hydropersulfides; Nitroxides; Perthiyl radicals; Polysulfides; S-nitrosothiols; Thiols
Spectrochim Acta A Mol Biomol Spectrosc. 2000 Feb 1;56A(2):373-8
10727155
J Am Chem Soc. 2001 Sep 12;123(36):8868-9
11535101
J Am Chem Soc. 2003 Jan 22;125(3):789-95
12526680
J Inorg Biochem. 2003 Jan 1;93(1-2):52-60
12538052
J Biol Chem. 1961 Nov;236:3051-7
13890839
Free Radic Res Commun. 1991;12-13 Pt 1:187-94
1649088
J Phys Chem A. 2007 Dec 27;111(51):13595-605
18052257
Free Radic Biol Med. 2008 Jun 15;44(12):2013-8
18381080
J Phys Chem B. 2009 May 7;113(18):6378-96
19366259
Sci Signal. 2009 Apr 28;2(68):re2
19401594
Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1998-2004
20634473
Naunyn Schmiedebergs Arch Pharmacol. 2011 Apr;383(4):403-13
21336541
Exp Physiol. 2011 Sep;96(9):840-6
21666033
Arch Biochem Biophys. 2011 Dec 15;516(2):146-53
22001739
Mol Cell. 2012 Jan 13;45(1):13-24
22244329
Antioxid Redox Signal. 2013 May 20;18(15):1906-19
23176571
ACS Chem Biol. 2013;8(6):1283-90
23547844
ACS Chem Biol. 2013;8(6):1110-6
23557648
Circulation. 2013 Jun 25;127(25):2523-34
23704252
Nitric Oxide. 2014 Sep 15;41:4-10
24491257
Redox Biol. 2014 Jan 11;2:234-44
24494198
Proc Natl Acad Sci U S A. 2014 May 27;111(21):7606-11
24733942
Chembiochem. 2014 Nov 3;15(16):2361-4
25205314
Free Radic Biol Med. 2014 Dec;77:82-94
25229186
ACS Chem Neurosci. 2014 Oct 15;5(10):876-83
25230373
Nitric Oxide. 2015 Apr 30;46:93-101
25512332
Free Radic Biol Med. 2015 Jul;84:227-245
25843657
Nat Rev Drug Discov. 2015 May;14(5):329-45
25849904
Inorg Chem. 2015 Oct 5;54(19):9367-80
26111441
Handb Exp Pharmacol. 2015;230:61-81
26162829
Handb Exp Pharmacol. 2015;230:233-41
26162838
Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):E4651-60
26224837
Arch Biochem Biophys. 2015 Dec 15;588:15-24
26519887
Sci Adv. 2016 Jan 22;2(1):e1500968
26844296
Biochem J. 1989 Dec 15;264(3):625-32
2695062
Free Radic Biol Med. 2016 Aug;97:136-147
27242269
Chem Sci. 2016 Oct 1;7(10):6347-6356
28567247
Biochem Biophys Res Commun. 1987 Apr 29;144(2):1037-42
3034255
Eur J Biochem. 1970 May 1;14(1):169-74
5447431
J Biochem. 1981 Jun;89(6):1913-21
7287665
Methods Enzymol. 1995;251:55-69
7651231
Free Radic Res. 1994 Jun;20(6):387-400
8081454
J Mol Spectrosc. 1997 Sep;185(1):153-7
9344806