Open access peer-reviewed chapter - ONLINE FIRST

Functional Mimics of Glutathione Peroxidase: Spirochalcogenuranes, Mechanism and Its Antioxidant Activity

Written By

Devappa S. Lamani

Submitted: December 2nd, 2021 Reviewed: January 3rd, 2022 Published: April 14th, 2022

DOI: 10.5772/intechopen.102430

Chalcogens Edited by Dhanasekaran Vikraman

From the Edited Volume

Chalcogens [Working Title]

Prof. Dhanasekaran Vikraman

Chapter metrics overview

11 Chapter Downloads

View Full Metrics


The present chapter describe a series of synthetic organoselenium compounds such as ebselen analogues, diaryl selenides, spirodioxyselenurane, spirodiazaselenuranes and its Glutathione peroxidise (GPx) catalytic activity. These ebselen related compounds either by modifying the basic structure of ebselen or incorporating some structural features of the native enzyme, a number of small-molecules of selenium compounds as functional mimics of GPx are discussed. In addition to this, spirodioxyselenuranes and spirodiazaselenuranes are important class of hypervalent selenium compounds, whose stability highly depends on the nature of the substituents attached to the nitrogen atom. The glutathione peroxidase (GPx) mimetic activity of all the selenium compounds showed significantly by facilitating the oxidation of the selenium centre. In contrast to this, ebselen analogue shows significant antioxidant activity compared with spirodiazaselenuranes and its derivatives.


  • spirodiazaselenuranes
  • antioxidant activity
  • selenoenzymes
  • ebselene

1. Introduction

Selenium has been discovered by the Swedish scientist Jons Jakob Berzelius in 1818. The chemistry of selenium, the next element to sulfur in the chalcogen group, is very less explored as compared to the chemistry of sulfur [1]. The diethyl selenide was synthesized by Lowig in 1836 and it was obtained in pure form in 1869 ass first synthetic selenium compound [2, 3]. Selenium chemistry was initially mainly focused on the synthesis of simple diselenides (RSeSeR), selenols (RSeH) etc. However, due to the unpleasant odor of selenols and aliphatic selenides, and also its toxicity the selenium chemistry faced a serious setback. Furthermore, due to toxicity of selenium was associated with diseases such as liverstock disease [4], intoxication in experimental animals [5, 6, 7] etc., therefore, it was considered a toxic element. In 1954 by Pinsent was established with the beneficial effect of selenium for living organisms the discovery that certain bacteria grew faster in selenium fortified medium [8]. However, the exact role of selenium responsible for the growth of bacteria was not clear. Almost after 20 years of this discovery, in 1973, it was found that two bacterial enzymes, formate dehydrogenase and glycine reductase contain selenium in their active sites [9, 10]. Flohe and co-workers was discovered almost at the same time the importance of selenium to mammals [11]. They found that the mammalian enzyme glutathione peroxidase (GPx), contains a selenocysteine residue in its active site. Nowadays the major selenoenzymes discovered to date include formate dehydrogenases [12], hydrogenases [13, 14, 15, 16], glycine reductase [17] iodothyronine deiodinases (ID) [18, 19, 20, 21, 22], thioredoxin reductases (TrxR) [23, 24, 25, 26], selenophosphate synthetase [27], and selenoprotein P [28, 29], glutathione peroxidase (GPx) [30, 31, 32, 33].

1.1 Glutathione peroxidase

Glutathione peroxidase (GPx) an mammalian enzyme, contains selenocysteine residue in its active site, For the last four decades, an extensive research has been carried out on the mammalian antioxidant enzymes GPx [34]. The cGPx utilizes glutathione (GSH) as reducing substrate exclusively for the reduction of H2O2 and organic hydroperoxides such as tert-butyl hydroperoxide (t-BuOOH) and cumene hydroperoxide (Cum-OOH). This enzyme exhibits good activity with all phospholipid hydroperoxides, fatty acid hydroperoxides, t-BuOOH, Cum-OOH, cholesterol hydroperoxides, and H2O2. The crystal structure of GPx indicates that the Sec residue (Sec45) forms a ‘catalytic triad’ with other two amino acids, glutamine (Gln80) and tryptophan (Trp158) (Figure 1) [36].

Figure 1.

(a) Catalytic triad at the active site of GPx; (b) active site of glutathione peroxidase (PDB code 1GP1) determined by X-ray crystallography [35].

The crystal structure of the seleninic acid form of human pGPx also indicates that Gln79 and Trp153 are located within hydrogen bonding distance of the selenium atom (Figure 1). These residues appear to play an important functional role in their catalytic mechanisms.

A catalytic cycle of GPx (Figure 2) starts with the oxidation of the selenol (ESeH) moiety of Sec residue by peroxide to generate the selenenic acid (ESeOH) [37, 38], which reacts with cellular thiol (glutathione, GSH) to generate a selenenyl sulfide intermediate (ESeSG).

Figure 2.

Proposed mechanism for the GPx-catalyzed reduction of H2O2.

Another equivalent of GSH cleaves the -Se-S- bond in the selenenyl sulfide intermediate to regenerate the selenol with elimination of glutathione disulfide (GSSG). The cellular level concentration of GSH is maintained by glutathione reductase (GR) [39], which reduces GSSG to GSH by using NADPH as cofactor. The overall catalytic mechanism, two equivalents of NADPH is consumed to reduce one equivalent of peroxide. At very high concentrations of hydroperoxide the selenium centre in GPx may be overoxidized to produce seleninic acid (ESeO2H) and selenonic acid (ESeO3H). Whereas the oxidation of selenenic acid to seleninic acid is reversible in the presence of GSH, the further oxidation to selenonic acid may inactivate the enzyme.


2. Mimics and models of glutathione peroxidase

2.1 Ebselen analogues as GPx mimics/models

Synthetic selenium compounds with significant GPx activity have potential therapeutic applications (Figure 3). The first synthetic compound that has been shown to mimic the GPx activity was ebselen ([2-phenyl-1,2-benzisoselenazole-3)-(2H)-one] (1) [40, 41, 42, 43]. Furthermore, the synthesis of such compounds may help in understanding the chemistry at the active site of GPx. The initial success of ebselen was mainly due to its very low toxicity and high stability of the selenazole moiety does not allow the elimination of selenium during the biotransformations. Therefore, the selenium metabolism of this compound does not interfere with the organism and as a result ebselen used in clinical trials for the treatment of patients suffering from active ischemia stroke.

Figure 3.

Some representative examples of Ebselen analogues as GPx mimics.

In literature there were a several animal model studies have demonstrated that ebselen reduces oxidative stress in ischemia-reperfusion in heart and that it exhibits promising neuroprotective effect in brain. In addition to this, ebselen can be toxic to cells suggested in recent evidences. It has been shown that ebselen inhibits certain cell growth and induces apoptosis. However, the mechanism underlying the toxicity of ebselen is not known, the cellular glutathione (GSH) level appears to be depleted by ebselen. The GSH depletion increases the susceptibility of cells to oxidant injury as the reduced GSH is important for cell survival.

After the discovery that ebselen exhibits significant antioxidant activity by mimicking the active site of GPx, much attention has been devoted to the design and synthesis of novel analogues of ebselen. The ebselen homolog 2, tetrahedral carbon is incorporated into the heterocycle, retains the Se-N bond essential for the GPx activity. The selenazole model system 3has been used extensively to understand the antioxidant redox chemistry of selenocysteine at the active site of GPx and several such compounds has been synthesized and evaluated for its GPx activity (Figure 4) [44].

Figure 4.

Proposed catalytic cycle of ebselen and related compounds [45,46].

According to this mechanism the corresponding selenenyl sulfide is mainly the reaction of ebselen 1with a thiol (RSH). The obtained intermediate compound is found to be unstable in the assay system, and therefore, undergoes a disproportionation reaction to generate the stable diselenide. Subsequent reaction of with peroxide produces the selenenic acid and seleninic acid. During this mechanism when RSH is depleted in the reaction mixture, the seleninic acid and interestingly, the selenenic acid having a free N-H moiety undergoes cyclization to regenerate ebselen1 [45].

Back and co-workers [46], reported the catalytic cycle of di(3-hydroxy-propyl) selenide 9and acts an efficient catalyst for the reduction of t-BuOOH in the presence of BnSH. The compound 9involves the formation of an unusual spirodioxyselenurane 10. The oxidation of compound 9with t-BuOOH produces the transient selenoxide 10, which undergoes a spontaneous cyclization to produce the dioxyselenurane 11isolated compound structure was confirmed by spectroscopic methods and single X-ray crystallography.

The reaction of 11with BnSH produces an intermediate 12, which upon reaction with second equivalent of BnSH regenerates the selenide 9with elimination of BnSSBn (Figure 5). When t-BuOOH is present in the reaction mixture, compound 10is recyclized to compound 11. Although the reactivity of compound 9was only about 15times higher than that of ebselen under indentical condition, the catalytic mechansium involves the formation of an unusual spiro compound [47].

Figure 5.

Catalytic cycle of selenide9[47].


3. Spirochalcogenuranes

3.1 Spirodioxyselenuranes/spirodiazaselenurane and its analogues as GPx mimics/models

Lesser and Weiss in 1914 reported the first example of a spirodioxyselenurane 13. After this initial study, several spirodioxyselenuranes such as 14–19have been reported in the literature [48, 49, 50]. This type of hypervalent selenium compounds attracted significant attention in recent years due to their interesting structural and stereochemical properties [51]. The selenium center in spirodioxyselenuranes generally shows trigonal bipyramidal geometry around central atom with the lone pair lying in the equatorial plane and the electronegative oxygen atoms occupying the apical positions [52]. In contrast to the well-studied spirodioxyselenuranes, spirodiazaselenuranes that contain two nitrogen substituents are extremely rare. Back and co-workers [53] few years ago, demonstrated the relative instability of spirodiazaselenuranes. They reported that the oxidation of the selenium center in 2,2′-selenobis(benzamide) by H2O2 does not produce the expected spirodiaza derivative 8, but it results in the formation of azaselenonium hydroxide 23[54]. The azaselenonium cation contains one Se–N bond and the compound is stabilized by a noncovalent interaction between the selenium atom and the carbonyl oxygen atom of the other amide moiety (Figure 6).

Figure 6.

Some representative examples of stable spirochalcogenuranes [47,50,53,55].

In continuation selenium compounds in 2004 Back and co-workers reported for the first time that spirodioxyselenurane and its tellurium analogue exhibit very good antioxidant activity by mimicking the glutathione peroxidase (GPx) enzyme which protects the organism from oxidative damage by catalyzing the reduction of peroxides using thiol as the cofactor [47, 56]. Subsequently, a series of spirodioxyselenuranes with different stereochemistry and ring size has been reported [50, 54]. Very recently, we have reported the first example of a hydrolytically stable spirodiazaselenurane 24and its tellurium analogue 25bearing two nitrogen substituents in the apical positions [57]. In continuation of our research work on selenium compounds we have synthesized different substituted spirodiazaselenurane and its analogues and its Antioxidant activity [58, 59]. Very recently, Singh and co-workers have synthesized and characterized a new pincer type bicyclic diazaselenurane 26where the two amide groups are present in the same phenyl ring forming the bicycles [55].

3.2 Glutathione peroxidase (GPx) activity

Back and co-workers reported that spirodioxyselenurane 11exhibit excellent antioxidant property by mimicking glutathione peroxidise enzyme [47]. The effect of different substituents attached to the nitrogen atom was one of the objectives of this study to understand the antioxidant activity of selenides and spirodiazaselenuranes. Therefore, the GPx-like catalytic activity of compounds 27was studied using glutathione (GSH) as thiol cofactor and hydrogen peroxide (H2O2) as substrate [57, 58]. The reduction of H2O2 by the selenides mechanism may involve a redox shuttle between the selenides and spirodiazaselenuranes via the corresponding intermatidates selenoxides (Figure 5). As previously described, the reactions of compounds 27with H2O2 produce the corresponding selenoxides 28which upon elimination of a water molecule generate the spirodiazaselenuranes 29. Selenides 27regenerate by GSH due to the reductive cleave of the Se-N bonds in compounds 30(Path A, Figure 7). This pathway is particularly favored at higher concentrations peroxide.

Figure 7.

Proposed mechanism for GPx activity of compounds27–30[57,58].

The nucleophilic attack of the thiol at the selenium center may produce the intermediates 30which upon reaction with GSH can regenerate the selenides at higher concentrations of GSH. The nucleophilic attack of GSH at the selenium center is expected to favor due to noncovalent interactions between the selenium and one of the carbonyl oxygen. It should be noted that the mechanism shown in Figure 7 is different from that of GPx and other diselenide-based mimetics that utilize a selenol moiety for the reduction of peroxides.

3.3 Mechanism of spirocyclization

Detailed mechanistic studies of spirodiazaselenuranes and structural characterization were carried out by using 77Se NMR spectroscopy. It was observed in the previous studies the presence of aromatic substituents cyclization process is very rapid at room temperature (25°C) on the nitrogen atoms as apical position [58]. To detect intermediates at room temperature (25°C) the cyclizations of the selenides to the corresponding spiro compounds were too fast. However, the formation of selenoxide could be observed when the cyclization is blocked by replacing the N-H moiety in compound 29with an N-Et group. Therefore, the oxidation of selenide 29by H2O2 produced the selenoxide 30with very good yield.

However, it was observed when a solution of compound 31in acetonitrile with H2O2 was kept for a week, formation of the corresponding spirodioxyselenurane 32. The mechanism for the formation of 33may proceed via the initial attack of a water molecule at the selenium center in compound 31followed by a nucleophilic attack of the selenium-bound oxygen atom at the carbonyl carbon of one of the amide moieties, leading to the formation of an intermediate 32(Figure 8) [59]. Although the formation of a spirodioxyselenurane has been proposed for a selenide having an N-methyl-N-phenylamide moiety [55, 58, 59] the conversion of 31into 33suggests that such mechanism can be generalized for diaryl selenides having different substituents on the amide nitrogen atom as mentioned in Figure 9.

Figure 8.

Formation of spirodioxyselenurane from diaryl selenide by an oxidation-elimination mechanism [58].

Figure 9.

Stepwise mechanism for the formation of Spirodiazachalcogenuranes from diaryl selenide [58,60].


4. Conclusions

In conclusion, a series of ebselen, diaryl selenides and spirodiazaselenuranes and its glutathione peroxidase (GPx) activity were discussed. A detailed mechanistic study suggests that the spirocyclization occurs viathe formation of selenoxide intermediates. The glutathione peroxidase (GPx) mimetic activity of the selenides and the spirodiazaselenuranes indicates that the substituents attached to nitrogen atom have significant effect on the activity. Therefore, the selenoxide intermediates involved in the cyclization process could be isolated at the room temperature when it reacts with methyl halide. The comparison of the GPx-like activity showed that the antioxidant activity of diaryl selenids shows significant antioxidant activity due to oxidation of selenium and followed by the addition of H2O2 leads to spiro-compounds. Therefore, these compounds can provide a better protection against reactive oxygen species like H2O2 and peroxynitrite.



This study was supported by the Department of Science and Technology (DST), New Delhi. DSL thanks the UGC for the award of Dr. D. S. Kothari postdoctoral research fellowship and Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore. In addition author thanks to Prof. CNR Rao Research Centre Basaveshwar Science College, Bagalkot for support and encouragements.


  1. 1. Berzelius JJ. Undersökning af enny Mineral-kropp, funnen ide orenare sorterna af detvid Fahlun tillverkade svafle, Discovery of Selenium. Afhandlingar i Fysik, Kemi och Mineralogi. 1818;6:42
  2. 2. Löwig CJ.Poggendorff’sUeber schwefelwasserstoff-und selenwasserstoffäther (about hydrogen sulfide and selenium hydrogen ether). Annals of Physics. 1836;37:552
  3. 3. Rathke B. Ueber das Selenmercaptan. Justus Liebigs Annalen der Chemie. 1869;152:211
  4. 4. Hutton JG. The correlation of certain lesions in animals with certain soil types. Journal of the American Chemical Society. 1931;23:1076
  5. 5. Franke KW. A toxicant occurring naturally in certain samples of plant foodstuffs. I. Results obtained in preliminary feeding trials. The Journal of Nutrition. 1934;8:597
  6. 6. Franke KW, Potter VR. A new toxicant occurring naturally in certain samples of plant foodstuffs. IX. Toxic effects of orally ingested selenium. The Journal of Nutrition. 1934;8:615
  7. 7. Franke KW, Painter EP. A new toxicant occurring naturally in certain samples of plant foodstuffs. XIV. The effect of selenium containing foodstuffs on growth and reproduction of rats at various ages. The Journal of Nutrition. 1936;10:599
  8. 8. Pinsent J. The need for selenite and molybdate in the formation of formic dehydrogenase by members of thecoli-aerogenesgroup of bacteria. The Biochemical Journal. 1954;57:10
  9. 9. Andreesen R, Ljungdahl L. Formate dehydrogenase ofClostridium thermoaceticum: Incorporation of Selenium-75, and the effects of selenite, Molybdate, and tungstate on the enzyme. Journal of Bacteriology. 1973;116:867
  10. 10. Turner DC, Stadtman TC. Purification of protein components of the clostridial glycine reductase system and characterization of protein a as a selenoprotein. Archives of Biochemistry and Biophysics. 1973;154:366
  11. 11. Flohe L, Günzler EA, Schock HH. Glutathione peroxidase-selenoenzyme. FEBS Letters. 1973;32:132
  12. 12. Boyington JC, Gladyshev VN, Khangulov SV, Stadtman TC, Sun PD. Crystal structure of formate dehydrogenase H: Catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 cluster. Science. 1997;275:1305
  13. 13. Wilting R, Schorling S, Persson BC, Bock A. Selenoprotein synthesis in archaea: Identification of an mRNA element ofMethanococcus jannaschiiprobably directing selenocysteine insertion. Journal of Molecular Biology. 1997;266:637
  14. 14. Garcin E, Vernede X, Hatchikian EC, Volbeda A, Frey M, Fontecilla-Camps JC. The crystal structure of a reduced[NiFeSe] hydrogenase provides an image of the activity catalytic center. Structure. 1999;7:557
  15. 15. Pfeiffer M, Bingemann R, Klein A. Fusion of two subunits does not impair the function of a [NiFeSe]-hydrogenase in the archaeonMethanococcus voltae Eur. Journal of Biochemistry. 1998;256:447
  16. 16. Wagner M, Sonntag D, Grimm R, Pich A, Eckerskorn C, Söhling B, et al. Substrate-specific selenoprotein B of glycine reductase fromEubacterium acidaminophilum. European Journal of Biochemistry. 1999;260:38
  17. 17. Behne D, Kyriakopoulos A, Meinhold H, Köhrle J. Identification of type I iodothyronine 5′-deiodinase as a selenoenzyme. Biochemical and Biophysical Research Communications. 1990;173:1143
  18. 18. Arthur JR, Nicol F, Beckett GJ. Hepatic iodothyronine 5′-deiodinase. The role of selenium. Biochemical Journal. 1990;272:537
  19. 19. Davey JC, Becker KB, Schneider MJ, Germain DL, Galton VA. Cloning of a cDNA for the type II Iodothyronine Deiodinase. The Journal of Biological Chemistry. 1995;270:26786
  20. 20. Croteau W, Whittemore SK, Schneider MJ, Germain DL. Cloning and expression of a Cdna for a mammalian type III Iodothyronine Deiodinase. The Journal of Biological Chemistry. 1995;270:16569
  21. 21. Lescure A, Gautheret D, Carbon P, Krol A. Novel selenoproteins identified in silico and in viva by using a conserved RNA structural motif. The Journal of Biological Chemistry. 1999;274:38147
  22. 22. Tamura T, Stadtman TC. A new selenoprotein from human lung adenocarcinoma cells: Purification, properties, and thioredoxin reductase activity. Proceedings of the National Academy of Sciences of the United States of America. 1996;93:1006
  23. 23. Lee SR, Kim JR, Kwon KS, Yoon HW, Leveine RL, Ginsburg A, et al. Molecular cloning and Charactrisation of a Mitochandrial Selenocysteine-containing Thioredoxin Reductase from rat liver. The Journal of Biological Chemistry. 1999;274:4722
  24. 24. Mustacich D, Powis G. Thioredoxin reductase. The Biochemical Journal. 2000;346:1
  25. 25. Watabe S, Makino Y, Ogawa K, Hiroi T, Yamamoto Y, Takahashi SY. Mitochondrial thioredoxin reductase in bovine adrenal cortex its purification, properties, nucleotide/amino acid sequences, and identification of selenocysteine. European Journal of Biochemistry. 1999;264:74
  26. 26. Mills GC. Hemoglobin catabolism I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. The Journal of Biological Chemistry. 1957;229:189
  27. 27. Motsenbocker MA, Tappel AL. Effect of dietary selenium on plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase in the rat. The Journal of Nutrition. 1984;114:279
  28. 28. Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochimica et Biophysica Acta. 1982;710:197
  29. 29. Takahashi K, Avissar N, Whittin J, Cohen H. Purification and characterization of human plasma glutathione peroxidase: A selenoglycoprotein distinct from the known cellular enzyme. Archives of Biochemistry and Biophysics. 1987;256:677
  30. 30. Chu FF, Doroshow JH, Esworthy RS. Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. Journal of Biological Chemistry. 1993;268:2571
  31. 31. Gromer S, Eubel JK, Lee BL, Jacob J. Human selenoproteins at a glance. Cellular and Molecular Life Sciences. 2005;62:2414
  32. 32. Flohé L. Glutathione peroxidase brought into focus in into focus. In: Pryor WA, editor. Free Radicals in Biology. Vol. 5. New York: Academic Press; 1982. p. 223
  33. 33. Maiorino M, Roveri A, Coassin M, Ursini F. Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51). Biochemical Pharmacology. 1988;37:2267
  34. 34. Epp O, Ladenstein R, Wendel A. The refined structure of the selenoenzyme Gultathione peroxidase at 0.2-nm resolution. European Journal of Biochemistry. 1983;133:51-69
  35. 35. Nogueira CW, Rocha JBT. Organoselenium and organotellurium compounds: Toxicology and pharmacology. In: Rappoport Z, editor. The Chemistry of Organic Selenium and Tellurium Compounds. Vol. 1, 2, Part-II, Chapter 21. New York: Wiley; 2012
  36. 36. Mukherjee AJ, Zade SS, Singh HB, Sunoj RB. Organoselenium chemistry: Role of intramolecular interactions. Chemical Reviews. 2010;110:4357
  37. 37. Müller A, Cadenas E, Graf P, Sies H. A novel biologically active seleno-organic compound-1: Gultathione peroxidase-like activity in vitro and antioxidant capacity of PZ-51(Ebselen). Biochemical Pharmacology. 1984;33:3235
  38. 38. Sies H, Matsumoto H. Ebselen as a glutathione peroxidase mimic and as a scavenger of peroxynitrite. Advances in Pharmacology. 1997;38:229-246
  39. 39. Fong MC, Schiesser CH. Reactions of 2,2′-diselenobis(N-alkylbenzamides) with peroxides: A free-radical synthesis ofEbselenand related analogues. Tetrahedron Letters. 1995;36:7329
  40. 40. Mugesh G, Singh HB. Synthetic organoselenium compounds as antioxidants: Glutathione peroxidase activity. Chemical Society Reviews. 2000;29:347
  41. 41. Mugesh G, Panda A, Singh HB, Punekar NS, R. J. Butcher gultathione peroxidase-like activity of diaryl diselenides-a mechanistic study. Journal of the American Chemical Society. 2001;123:839
  42. 42. Bhabak KP, Mugesh G. Synthesis, characterization and antioxidant activity of some ebselen analogues. Chemistry—A European Journal. 2007;13:4594
  43. 43. Bhabak KP, Mugesh G. Antioxidant activity of the anti-inflammantry compound ebselen; a reversible cyclisation pathway via selenenic and seleninic acid intermadates. Chemistry—A European Journal. 2008;14:8640
  44. 44. Bhabak KP, Mugesh G. Amide-based glutathione peroxidase mimics: Effect of secondry and tertiary amid sustituenets on antioxidant activity. Chemistry, an Asian Journal. 2009;4:974
  45. 45. Wirth T, Fragale G, Spichty M. Mechanistic course of the asymmetric Methoxyselenenylation reaction. Journal of the American Chemical Society. 1998;120:3376
  46. 46. Back TG, Moussa Z. Remarkable activity of a novel cyclic seleninate ester as glutathione peroxidase mimetic and its facile in situ generation from allyl-3-hydroxypropyl selenide. Journal of the American Chemical Society. 2003;125:13455
  47. 47. Back TG, Moussa Z, Parvez M. The exceptional glutathione peroxidase-like activity of Di(3-hydroxypropyl) Selenide and the unexpected role of a novel Spirodioxaselenanonane intermediate in the catalytic cycle. Angewandte Chemie, International Edition. 2004;43:1268
  48. 48. Lesser R, Weiss R. Über Selenoxanthon und Selenoxanthon-carbonsäure. Über selenhaltige aromatische Verbindungen ÜberBer.Dtsch. Chemische Berichte. 1914;47:2510-2525
  49. 49. Kapovits I, Kalman A. Formation and structure of a four-co-ordinate Organo-Sulphur (IV) compound. Chemical Communications. 1971;12:649-650
  50. 50. Takaguchi Y, Furukawa N. First synthesis and structural determination of 1, 1′-spirobis(3H-2, 1-benzoxatellurole)-3, 3′-dione ([10-Te-4(C202)]). Heteroatom Chemistry. 1995;6:481-484
  51. 51. Bhabak KP, Mugesh G. Functional mimics of glutathione peroxidase: Bioinspired synthetic antioxidants. Accounts of Chemical Research. 2010;43:1408-1419
  52. 52. Zhang Z, Takahashi S, Saito S, Koizumi T. First synthesis and stereochemistry of enantiomerically pure spiroselenurane and spirotellurane using the 2-exo-hydroxy-10-bornyl group as a chiral ligand. Tetrahedron: Asymmetry. 1998;9:3303-3317
  53. 53. Zhang J, Saito S, Koizumi T. Acidic and basic hydrolysis of an optically pure Spiro-λ4-sulfurane: Completely opposite Stereochemical outcome. Journal of the American Chemical Society. 1998;120:1631-1632
  54. 54. Kapovits I, Rabai J, Szabó D, Czako K, Kucsman A, Argay G, et al. Diaryldiacyloxyspirosulfuranes. Part 3. Sulfuranes with five-, six- and Sevenmembered Spirorings: Syntheses and molecular structures. Journal of Chemical Society, Perkin Transactions. 1993;2:847-853
  55. 55. Selvakumar K, Singh HB, Goel N, Singh UP, Butcher RJ. Synthesis and structural characterization of pincer type bicyclic diacyloxy- and diazaselenuranes. Dalton Transactions. 2011;40:9858-9867
  56. 56. Jacob C, Giles GI, Giles NM, Sies H. Sulfur and selenium: The role of oxidation state in protein structure and function. Angewandte Chemie, International Edition. 2003;42:4742-4758
  57. 57. Back TG, Kuzma D, Parvez M. Aromatic derivatives and tellurium analogues of cyclic Seleninate esters and spirodioxyselenuranes that act as glutathione peroxidase Mimetics. The Journal of Organic Chemistry. 2005;70:9230-9236
  58. 58. Sarma BK, Manna D, Minoura M, Mugesh G. Synthesis, structure, Spirocyclization mechanism, and glutathione peroxidase-like antioxidant activity of stable spirodiazaselenurane and spirodiazatellurane. Journal of the American Chemical Society. 2010;132:5364-5374
  59. 59. Lamani DS, Bhowmick D, Mugesh G. Substituent effects on the stability and antioxidant activity of spirodiazaselenuranes. Molecules. 2015;20:12959-12978
  60. 60. Lamani DS, Bhowmick D, Mugesh G. Spirodiazaselenuranes: Synthesis, structure and antioxidant activity. Organic & Biomolecular Chemistry. 2012;10:7933-7943

Written By

Devappa S. Lamani

Submitted: December 2nd, 2021 Reviewed: January 3rd, 2022 Published: April 14th, 2022