methaneseleninic acid

Methaneseleninic acid is conveniently synthesized through oxidation of commercially available dimethyl diselenide by 3% hydrogen peroxide.{{cite journal | last1 = Ip | first1 = C. | last2 = Thompson | first2 = H.J. | last3 = Zhu | first3 = Z. | last4 = Ganther | first4 = H.E. | year = 2000 | title = In vitro and in vivo studies of methylseleninic acid: evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention | journal = Cancer Res. | volume = 60 | issue = 11 | pages = 2882–2886 | pmid = 10850432}}

:{{chem2|CH3\sSe\sSe\sCH3 + H2O2 → 2 CH3\sSe(\dO)\sOH}}

Seleninic acids can be prepared by oxidation of selenoesters with one equivalent of dimethyldioxirane (DMDO). Use of excess DMDO affords little studied selenonic acids ({{chem2|R\sSe(\dO)2\sOH}}).{{cite journal | last1 = Abdo | first1 = M. | last2 = Knapp | first2 = S. | year = 2008 | title = Biomimetic seleninates and selenonates | journal = J. Am. Chem. Soc. | volume = 130 | issue = 29 | pages = 9234–9235 | doi = 10.1021/ja8034448 | pmid=18576651}}

:{{chem2|R\sSe\sC(\dO)\sR' + DMDO → R\sSe(\dO)\sOH}}

:{{chem2|R\sSe\sC(\dO)\sR' + excess DMDO → R\sSe(\dO)2\sOH}}

Selenenic acids, formed during the syn-elimination of selenoxides, undergo spontaneous disproportionation into the corresponding seleninic acids and diselenides:

:{{chem2|4 R\sSe\sOH → 2 R\sSe(\dO)\sOH + R\sSe\sSe\sR}}

Methaneseleninic acid, from decomposition of Se-methylselenocysteine Se-oxide but also available commercially, has been characterized by X-ray crystallography.{{cite journal | last1 = Block | first1 = E. | last2 = Birringer | first2 = M. | last3 = Jiang | first3 = W. | last4 = Nakahodo | first4 = T. | last5 = Thompson | first5 = H. J. | last6 = Toscano | first6 = P. J. | last7 = Uzar | first7 = H. | last8 = Zhang | first8 = X. | last9 = Zhu | first9 = Z. | year = 2001 | title = Allium chemistry: Synthesis, natural occurrence, biological activity, and chemistry of Se-alk(en)ylselenocysteines and their γ-glutamyl derivatives and oxidation products | journal = J. Agric. Food Chem. | volume = 49 | issue = 1 | pages = 458–470 | doi = 10.1021/jf001097b | pmid = 11305255}} The configuration about the selenium atom is pyramidal, with Se-C = 1.925(8) Å, Se-O = 1.672(7) Å, Se-OH = 1.756(7) Å, the angle OSeO = 103.0(3)°, the angle HO-Se-C = 93.5(3)°, and the angle OSeC = 101.4(3)°. The structure is isomorphous to that of methanesulfinic acid {{cite journal | last1 = Seff | first1 = K. | last2 = Heidner | first2 = E. G. | last3 = Meyers | first3 = M. | last4 = Trueblood | first4 = K. N. | year = 1969 | title = The crystal and molecular structure of methanesulfinic acid | journal = Acta Crystallographica Section B | volume = 25 | issue = 2 | pages = 350–354 | doi=10.1107/s0567740869002214| doi-access = free}} Optical isomers of methaneseleninic acid can be isolated as chiral crystals by recrystallization from a mixture of methanol and toluene. The absolute configuration of one of the enantiomers was determined by X-ray crystallography. Optically active methaneseleninic acid was stable toward racemization in the solid state, although it racemized very rapidly in solution.{{cite journal | last1 = Nakashima | first1 = Y. | last2 = Shimizu | first2 = T. | last3 = Hirabayashi | first3 = K. | last4 = Yasui | first4 = M. | last5 = Nakazato | first5 = M. | last6 = Iwasaki | first6 = F. | last7 = Kamigata | first7 = N. | year = 2005 | title = Optically active seleninic acid: Isolation, absolute configuration, stability, and chiral crystallization | journal = Bull. Chem. Soc. Jpn. | volume = 78 | issue = 4 | pages = 710–714 | doi = 10.1246/bcsj.78.710}}

Methaneseleninic acid shows potential anticancer activity and is a model for studying the anticancer effects of selenium in vitro.{{cite journal | last1 = Zhao | first1 = H. | last2 = Whitfield | first2 = M. L. | last3 = Xu | first3 = T. | last4 = Botstein | first4 = D. | last5 = Brooks | first5 = J. D. | year = 2003| title = Diverse effects of methylseleninic acid on the transcriptional program of human prostate cancer cells | journal = Molecular Biology of the Cell | volume = 15| issue = 2 | pages = 506–519 | doi = 10.1091/mbc.E03-07-0501 | pmid=14617803 | pmc=329225}} Methaneseleninic acid shows superior in vivo inhibitory efficacy toward human prostate cancer compared to selenomethionine or selenite (ion).{{cite journal | last1 = Li | first1 = G. X. | last2 = Lee | first2 = H. J. | last3 = Wang | first3 = Z. | last4 = Hu | first4 = H. | last5 = Liao | first5 = J. D. | last6 = Watts | first6 = J. C. | last7 = Combs | first7 = G. F. Jr. | last8 = Lu | first8 = J. | year = 2008 | title = Superior in vivo inhibitory efficacy of methylseleninic acid against human prostate cancer over selenomethionine or selenite | journal = Carcinogenesis | volume = 29 | issue = 5 | pages = 1005–1012 | doi=10.1093/carcin/bgn007| pmc = 3312608 | pmid=18310093}} It has recently been reported that methaneseleninic acid enhances the efficacy of paclitaxel for treatment of triple-negative breast cancer,{{cite journal | last1 = Qi | first1 = Y. | last2 = Fu | first2 = X. | last3 = Xiong | first3 = Z. | last4 = Zhang | first4 = H. | last5 = Hill | first5 = S.M. | last6 = Rowan | first6 = B.G. | last7 = Dong | first7 = Y. | year = 2012 | title = Methylseleninic acid enhances paclitaxel efficacy for the treatment of triple-negative breast cancer | journal = PLOS ONE | volume = 7 | issue = 2 | page = e31539 | doi = 10.1371/journal.pone.0031539 | pmid=22348099 | pmc=3279411| bibcode = 2012PLoSO...731539Q | doi-access = free}} that methaneseleninic acid functions as an aromatase inhibitor, of possible use in therapy for estrogen receptor-positive breast cancer in postmenopausal women,{{cite journal | last1 = Gao | first1 = R. | last2 = Zhao | first2 = L. | last3 = Liu | first3 = X. | last4 = Rowan | first4 = B.G. | last5 = Wabitsch | first5 = M. | last6 = Edwards | first6 = D.P. | last7 = Nishi | first7 = Y. | last8 = Yanase | first8 = T. | last9 = Yu | first9 = Q. | last10 = Dong | first10 = Y. | year = 2012 | title = Methylseleninic acid is a novel suppressor of aromatase expression | journal = J. Endocrinol. | volume = 212 | issue = 2 | pages = 199–205 | doi = 10.1530/JOE-11-0363 | pmid = 22128327 | doi-access = free}} that methaneseleninic acid shows promise as a sensitizing agent for apoptosis induced by the Bcl-2-family inhibitor ABT-737 in several cancer lines,{{cite journal | last1 = Yin | first1 = S | last2 = Dong | first2 = Y | last3 = Li | first3 = J | last4 = Fan | first4 = L | last5 = Wang | first5 = L | last6 = Lu | first6 = J | last7 = Vang | first7 = O | last8 = Hu | first8 = H | year = 2012 | title = Methylseleninic acid potentiates multiple types of cancer cells to ABT-737-induced apoptosis by targeting Mcl-1 and Bad | journal = Apoptosis | volume = 17 | issue = 4 | pages = 388–399 | doi = 10.1007/s10495-011-0687-9 | pmid = 22179721 | s2cid = 15423784}} and that methaneseleninic acid restricts tumor growth in the nude mouse model of metastatic breast cancer{{cite journal | last1 = Wu | first1 = X. | last2 = Zhang | first2 = Y. | last3 = Pei | first3 = Z. | last4 = Chen | first4 = S. | last5 = Yang | first5 = X. | last6 = Chen | first6 = Y. | last7 = Lin | first7 = D. | last8 = Ma | first8 = R.Z. | year = 2012 | title = Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2 | journal = BMC Cancer | volume = 12 | page = 192 | doi = 10.1186/1471-2407-12-192 | pmid=22640261 | pmc=3517305 | doi-access = free}} and Lewis lung carcinoma in mice.{{cite journal | last1 = Yan | first1 = L. | last2 = DeMars | first2 = L.C. | year = 2012 | title = Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice | journal = Int. J. Cancer | volume = 131 | issue = 6 | pages = 1260–1266 | doi = 10.1002/ijc.27355 | pmid = 22095442 | doi-access = free}}

Methaneselenol ({{chem2|CH3SeH}}) can be produced in vivo by reduction of methaneseleninic acid and may in fact be the key metabolite responsible for selenium’s anticancer activity{{cite journal | last1 = Ip | first1 = C. | last2 = Dong | first2 = Y. | last3 = Ganther | first3 = H. E. | year = 2002 | title = New concepts in selenium chemoprevention | journal = Cancer Metastasis Rev. | volume = 21 | issue = 3–4 | pages = 281–289 | doi = 10.1023/A:1021263027659 | pmid = 12549766 | s2cid = 7636317}} through generation of superoxide.{{cite journal | last1 = Spallholz | first1 = J.E. | last2 = Shriver | first2 = B.J. | last3 = Reid | first3 = T.W. | year = 2001 | title = Dimethyldiselenide and methylseleninic acid generate superoxide in an In vitro chemiluminescence assay in the presence of glutathione: Implications for the anticarcinogenic activity of L-selenomethionine and L-Se-methylselenocysteine | journal = Nutrition and Cancer | volume = 40 | issue = 1 | pages = 34–41 | doi = 10.1207/S15327914NC401_8 | pmid = 11799920 | s2cid = 26915557}} The reduction of methaneseleninic acid by mammalian thioredoxin reductase has been studied.{{cite journal | last1 = Snider | first1 = G. | last2 = Grout | first2 = L. | last3 = Ruggles | first3 = E. L. | last4 = Hondal | first4 = R. J. | year = 2010 | title = Methaneseleninic acid is a substrate for truncated mammalian thioredoxin reductase: Implications for the catalytic mechanism and redox signaling | journal = Biochemistry | volume = 49 | issue = 48 | pages = 10329–10338 | doi = 10.1021/bi101130t | pmid=21038895 | pmc=3018153}}

{{reflist}}

Category:Organoselenium compounds

Category:Organic acids

Category:Selenium(II) compounds