Selenenic acid

A selenenic acid is an organoselenium compound and an oxoacid with the general formula RSeOH, where R ≠ H. It is the first member of the family of organoselenium oxoacids, which also include seleninic acids and selenonic acids, which are RSeO₂H and RSeO₃H, respectively. Selenenic acids derived from selenoenzymes are thought to be responsible for the antioxidant activity of these enzymes. This functional group is sometimes called SeO-selenoperoxol.

Properties

Structure of an isolable selenenic acid.^[1]

In contrast to selenonic and seleninic acids, selenenic acids are unstable with respect to a self-condensation reaction to form the corresponding selenoseleninates^[2] or disproportionation into corresponding seleninic acids and diselenides:

2 RSeOH → RSe(O)SeR + H₂O

2 RSeOH → RSeO₂H + 1/2 RSeSeR

Even the very bulky 2,4,6-tri-tert-butylbenzeneselenenic acid disproportionates readily.^[3] A stable selenenic acid was synthesized by burying the SeOH functional group within the cavity of a p-tert-butyl[calix[6]arene macrocycle]. X-ray crystallographic analysis revealed the Se-O bond length to be 1.763 Å. The Se-O absorbs in the IR spectrum at 680–700 cm⁻¹.^[4] In a stable selenenic acid prepared by oxidizing a highly hindered selenol, BmtSeH, the Se-O bond length was found to be 1.808 Å while the O-Se-C angle was 96.90°. Oxidation of BmtSeOH gave BmtSeO₂H.^[5]

Selenenic acids are believed to be transient intermediates in a number of redox reactions involving organoselenium compounds. One notable example is the syn-elimination of selenoxides. Selenenic acids are also transient intermediates in the reduction of seleninic acids as well as the oxidation of diselenides. The reasoning for postulating selenenic acids as reactive intermediates is based in part on analogy with their more extensively studied sulfenic acid analogs.^[6]

Biology

Selenenic acids derived from selenocysteine are involved in cell signaling and certain enzymatic processes. The best known selenoenzyme, glutathione peroxidase (GPx), catalyzes the reduction of peroxides by glutathione (GSH). The selenenic acid intermediate (E-SeOH) is formed upon oxidation of the catalytically active selenol (E-SeH) by hydrogen peroxide. This selenenic acid derivative of the peroxidase then reacts with a thiol-containing cofactor (GSH) to generate the key intermediate selenenyl sulfide (E-SeSG). This intermediate is subsequently attacked by a second GSH to regenerate the selenol and the glutathione cofactor is released in its oxidized form, GSSG. The catalytic mechanism of GPx, involves selenol (R-SeH), selenenyl sulfide (R1-SeS-R2), and selenenic acid intermediates.^[7]

RSeH + H₂O₂ → RSeOH + H₂O

RSeOH + GSH → GS-SeR + H₂O

GS-SeR + GSH → GS-SG + RSeH

In the absence of thiols, selenols tend to overoxidize to produce seleninic acids. Many organoselenium compounds (selenenamides, diaryl diselenides) contain "interesting" biological activities. Their activity is attributed to their mimicry of glutathione peroxidase activity. They reduce hydroperoxides that otherwise convert to toxic byproducts and/or reactive oxygen species that can cause further damage to the cell.^[8]

References

^ Goto, Kei; Nagahama, Michiko; Mizushima, Tadashi; Shimada, Keiichi; Kawashima, Takayuki; Okazaki, Renji (2001). "The First Direct Oxidative Conversion of a Selenol to a Stable Selenenic Acid: Experimental Demonstration of Three Processes Included in the Catalytic Cycle of Glutathione Peroxidase". Organic Letters. 3 (22): 3569–3572. doi:10.1021/ol016682s. PMID 11678710.
^ A. Ishii, S. Matsubayashi, T. Takahashi, J. Nakayama, "Preparation of a selenenic acid and isolation of selenoseleninates" J. Org. Chem. 1999, 64, 1084–1085. doi:10.1021/jo982039g
^ H. J. Reich, C. P. Jasperse, "Organoselenium chemistry. Preparation and reactions of 2,4,6-tri-tert-butylbenzeneselenenic acid" J. Org. Chem. 1988, 53, 2389–2390. doi:10.1021/jo00245a056
^ T. Saiki, K. Goto, R. Okazaki, “Isolation and X-ray crystallographic analysis of a stable selenenic acid” Angew. Chem. Int. Ed. 1997, 36, 2223–2224. doi:10.1080/10426509808545976
^ K. Goto, M. Nagahama, T. Mizushima, K. Shimada, T. Kawahima, R. Okazaki, “The first direct oxidative conversion of a selenol to a stable selenenic acid: Experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase” Org. Lett. 2001, 3, 3569–3572. doi:10.1021/ol016682s
^ D. L. Klayman, W. H. H. Gunther Organic Selenium Compounds: Their Chemistry and Biology, Wiley, 1973. ISBN 0-471-49032-6
^ H. J. Forman, J. Fukuto, M.Torres, Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles, Kluwer, 2003. ISBN 1402011172
^ K. P. Bhabak, G. Mugesh, "Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants" Acc. Chem. Res., 2010, 43, 1408–1419. doi:10.1021/ar100059g

[1] Goto, Kei; Nagahama, Michiko; Mizushima, Tadashi; Shimada, Keiichi; Kawashima, Takayuki; Okazaki, Renji (2001). "The First Direct Oxidative Conversion of a Selenol to a Stable Selenenic Acid: Experimental Demonstration of Three Processes Included in the Catalytic Cycle of Glutathione Peroxidase". Organic Letters. 3 (22): 3569–3572. doi:10.1021/ol016682s. PMID 11678710.

[2] A. Ishii, S. Matsubayashi, T. Takahashi, J. Nakayama, "Preparation of a selenenic acid and isolation of selenoseleninates" J. Org. Chem. 1999, 64, 1084–1085. doi:10.1021/jo982039g

[3] H. J. Reich, C. P. Jasperse, "Organoselenium chemistry. Preparation and reactions of 2,4,6-tri-tert-butylbenzeneselenenic acid" J. Org. Chem. 1988, 53, 2389–2390. doi:10.1021/jo00245a056

[4] T. Saiki, K. Goto, R. Okazaki, “Isolation and X-ray crystallographic analysis of a stable selenenic acid” Angew. Chem. Int. Ed. 1997, 36, 2223–2224. doi:10.1080/10426509808545976

[5] K. Goto, M. Nagahama, T. Mizushima, K. Shimada, T. Kawahima, R. Okazaki, “The first direct oxidative conversion of a selenol to a stable selenenic acid: Experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase” Org. Lett. 2001, 3, 3569–3572. doi:10.1021/ol016682s

[6] D. L. Klayman, W. H. H. Gunther Organic Selenium Compounds: Their Chemistry and Biology, Wiley, 1973. ISBN 0-471-49032-6

[7] H. J. Forman, J. Fukuto, M.Torres, Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles, Kluwer, 2003. ISBN 1402011172

[8] K. P. Bhabak, G. Mugesh, "Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants" Acc. Chem. Res., 2010, 43, 1408–1419. doi:10.1021/ar100059g

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