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Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide

Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide
Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide

Manganese-centered porphyrins (MnPs), MnTE-2-PyP5+ (MnTE), MnTnHex-2-PyP5+ (MnTnHex), and MnTnBuOE-2-PyP5+ (MnTnBuOE) have received considerable attention because of their ability to serve as superoxide dismutase (SOD) mimetics thereby producing hydrogen peroxide (H2O2), and oxidants of ascorbate and simple aminothiols or protein thiols. MnTE-2-PyP5+ and MnTnBuOE-2-PyP5+ are now in five Phase II clinical trials warranting further exploration of their rich redox-based biology. Previously, we reported that SOD is also a sulfide oxidase catalyzing the oxidation of hydrogen sulfide (H2S) to hydrogen persulfide (H2S2) and longer-chain polysulfides (H2Sn, n = 3-7). We hypothesized that MnPs may have similar actions on sulfide metabolism. H2S and polysulfides were monitored in fluorimetric assays with 7-azido-4-methylcoumarin (AzMC) and 3',6'-di(O-thiosalicyl)fluorescein (SSP4), respectively, and specific polysulfides were further identified by mass spectrometry. MnPs concentration-dependently consumed H2S and produced H2S2 and subsequently longer-chain polysulfides. This reaction appeared to be O2-dependent. MnP absorbance spectra exhibited wavelength shifts in the Soret and Q bands characteristic of sulfide-mediated reduction of Mn. Taken together, our results suggest that MnPs can become efficacious activators of a variety of cytoprotective processes by acting as sulfide oxidation catalysts generating per/polysulfides.

2076-3921
1-19
Olson, Kenneth R.
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Gao, Yan
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Arif, Faihaan
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Patel, Shivali
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Yuan, Xiaotong
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Mannam, Varun
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Howard, Scott
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Batinic-Haberle, Ines
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Fukuto, Jon
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Minnion, Magdalena
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Feelisch, Martin
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Straub, Karl D.
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Olson, Kenneth R.
82b73d34-60b6-4915-9328-c50805bea090
Gao, Yan
23154085-596b-483e-8c31-79916fca87ea
Arif, Faihaan
5de29e3c-d981-4935-a68f-5dc861cb5526
Patel, Shivali
b6a7e388-0300-41e2-9645-a3810f0950d7
Yuan, Xiaotong
dcf9c337-fa50-4764-8c04-54129ed316f9
Mannam, Varun
91f2380a-d8ad-40be-87fd-20427347450f
Howard, Scott
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Batinic-Haberle, Ines
d4b041f5-8d4c-4100-966c-f6699cae7fed
Fukuto, Jon
b49c4f1a-3095-4154-821f-c3eee66d668b
Minnion, Magdalena
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Feelisch, Martin
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Straub, Karl D.
5cc49000-f71b-49ec-8e00-8fc21e29d293

Olson, Kenneth R., Gao, Yan, Arif, Faihaan, Patel, Shivali, Yuan, Xiaotong, Mannam, Varun, Howard, Scott, Batinic-Haberle, Ines, Fukuto, Jon, Minnion, Magdalena, Feelisch, Martin and Straub, Karl D. (2019) Manganese porphyrin-based SOD mimetics produce polysulfides from hydrogen sulfide. Antioxidants, 8 (12), 1-19. (doi:10.3390/antiox8120639).

Record type: Article

Abstract

Manganese-centered porphyrins (MnPs), MnTE-2-PyP5+ (MnTE), MnTnHex-2-PyP5+ (MnTnHex), and MnTnBuOE-2-PyP5+ (MnTnBuOE) have received considerable attention because of their ability to serve as superoxide dismutase (SOD) mimetics thereby producing hydrogen peroxide (H2O2), and oxidants of ascorbate and simple aminothiols or protein thiols. MnTE-2-PyP5+ and MnTnBuOE-2-PyP5+ are now in five Phase II clinical trials warranting further exploration of their rich redox-based biology. Previously, we reported that SOD is also a sulfide oxidase catalyzing the oxidation of hydrogen sulfide (H2S) to hydrogen persulfide (H2S2) and longer-chain polysulfides (H2Sn, n = 3-7). We hypothesized that MnPs may have similar actions on sulfide metabolism. H2S and polysulfides were monitored in fluorimetric assays with 7-azido-4-methylcoumarin (AzMC) and 3',6'-di(O-thiosalicyl)fluorescein (SSP4), respectively, and specific polysulfides were further identified by mass spectrometry. MnPs concentration-dependently consumed H2S and produced H2S2 and subsequently longer-chain polysulfides. This reaction appeared to be O2-dependent. MnP absorbance spectra exhibited wavelength shifts in the Soret and Q bands characteristic of sulfide-mediated reduction of Mn. Taken together, our results suggest that MnPs can become efficacious activators of a variety of cytoprotective processes by acting as sulfide oxidation catalysts generating per/polysulfides.

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Accepted/In Press date: 6 December 2016
e-pub ahead of print date: 12 December 2019
Published date: December 2019

Identifiers

Local EPrints ID: 439471
URI: http://eprints.soton.ac.uk/id/eprint/439471
ISSN: 2076-3921
PURE UUID: 2d6513e5-0eea-4304-b4dc-39c209c527e8
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 23 Apr 2020 16:54
Last modified: 26 Nov 2021 02:58

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Contributors

Author: Kenneth R. Olson
Author: Yan Gao
Author: Faihaan Arif
Author: Shivali Patel
Author: Xiaotong Yuan
Author: Varun Mannam
Author: Scott Howard
Author: Ines Batinic-Haberle
Author: Jon Fukuto
Author: Magdalena Minnion
Author: Martin Feelisch ORCID iD
Author: Karl D. Straub

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