Thiyl radical

In chemistry, a thiyl radical has the formula RS, sometimes written RS• to emphasize that they are free radicals. R is typically an alkyl or aryl substituent. Because S–H bonds are about 20% weaker than C–H bonds, thiyl radicals are relatively easily generated from thiols RSH.[1] Thiyl radicals are intermediates in the thiol-ene reaction, which is the basis of some polymeric coatings and adhesives. They are generated by hydrogen-atom abstraction from thiols using initiators such as AIBN:[2]

RN=NR → 2 R• + N2
R• + R′SH → R′S• + RH

Thiyl radicals are also invoked as intermediates in some biochemical reactions.

Thiyl radical in biology

Reactivity of Thiyl Radicals

The formation of thiyl radicals in vivo primarily occurs through the action of various radicals on the amino acid cysteine incorporated into proteins. The rate of radical formation is highest with the OH· radical (k = 6.8 x 109 M-1s-1)[3] and decreases through the H· radical (k = 6.8 x 109 M-1s-1)[3] down to peroxyl radicals R-CHOO· (k = 4.2 x 103 M-1s-1). One of the most important substrates of thiyl radicals in biological systems is lipids, where thiyl radicals play a crucial role in lipid peroxidation.[4] In this process, thiyl radicals act as chain transfer catalysts by transferring the unpaired electron to a new lipid, thereby accelerating lipid peroxidation.[4] Other substrates of thiyl radicals include other proteins (k = 1.4 x 105 M-1s-1),[5] monounsaturated fatty acids (MUFAs) (k = 1.6 x 105 M-1s-1),[6] and ubiquinone (k = 2.5 x 103 M-1s-1). Interestingly, the addition of lipophilic thiols in cell culture or administration to C. elegans accelerated lipid peroxidation at the same initiation rate, caused damage to membrane proteins, and was associated with a decline in polyunsaturated fatty acids (PUFAs) and a shortened lifespan.[7][8]

Elimination of Thiyl Radicals

The most important phenolic antioxidants, such as ubiquinone or α-tocopherol, are not suitable scavengers of thiyl radicals.[4] Both substances are not sufficiently reactive,[9][10][11] and α-tocopherol is also not present in sufficient quantities to scavenge thiyl radicals. Nonetheless, both compounds have high rate constants for their reaction with peroxyl radicals, highlighting their evolutionary importance as scavengers.[12][13][14] Isoprenoid polyenes, such as carotenoids or lycopene, exhibit very high rate constants regarding thiyl radicals (up to 109 M-1s-1).[15] However, even with excessive supplementation, the effect of lycopene is not sufficient to adequately counteract lipid peroxidation.[4] The situation is significantly more promising in aqueous media: ascorbic acid and glutathione also have high rate constants (>108 M-1s-1) and are present in sufficiently high concentrations, so in aqueous environments, thiyl radicals can be effectively neutralized by the aforementioned antioxidants.

References

  1. ^ Dénès, F.; Pichowicz, M.; Povie, G.; Renaud, P. (2014). "Thiyl Radicals in Organic Synthesis". Chemical Reviews. 114 (5): 2587–2693. doi:10.1021/cr400441m. PMID 24383397.
  2. ^ Hoyle, C. E.; Lee, T. Y.; Roper, T. (2004). "Thiol–enes: Chemistry of the Past with Promise for the Future". Journal of Polymer Science Part A: Polymer Chemistry. 42 (21): 5301–5338. Bibcode:2004JPoSA..42.5301H. doi:10.1002/pola.20366.
  3. ^ a b Tartaro Bujak, Ivana; Mihaljević, Branka; Ferreri, Carla; Chatgilialoglu, Chryssostomos (2016-11-01). "The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid". Free Radical Research. 50 (sup1): S18 – S23. doi:10.1080/10715762.2016.1231401. ISSN 1071-5762. PMID 27776460.
  4. ^ a b c d Moosmann, Bernd; Hajieva, Parvana (2022-04-29). "Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge". Antioxidants. 11 (5): 885. doi:10.3390/antiox11050885. ISSN 2076-3921. PMC 9137623. PMID 35624747.
  5. ^ Nauser, Thomas; Pelling, Jill; Schöneich, Christian (2004-10-01). "Thiyl Radical Reaction with Amino Acid Side Chains: Rate Constants for Hydrogen Transfer and Relevance for Posttranslational Protein Modification". Chemical Research in Toxicology. 17 (10): 1323–1328. doi:10.1021/tx049856y. ISSN 0893-228X.
  6. ^ Chatgilialoglu, Chryssostomos; Ferreri, Carla (2005-06-01). "Trans Lipids: The Free Radical Path". Accounts of Chemical Research. 38 (6): 441–448. doi:10.1021/ar0400847. ISSN 0001-4842. PMID 15966710.
  7. ^ Heymans, Victoria; Kunath, Sascha; Hajieva, Parvana; Moosmann, Bernd (2021-11-08). "Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs". Molecules. 26 (21): 6743. doi:10.3390/molecules26216743. ISSN 1420-3049. PMC 8586999. PMID 34771157.
  8. ^ Kunath, Sascha; Schindeldecker, Mario; De Giacomo, Antonio; Meyer, Theresa; Sohre, Selina; Hajieva, Parvana; von Schacky, Clemens; Urban, Joachim; Moosmann, Bernd (September 2020). "Prooxidative chain transfer activity by thiol groups in biological systems". Redox Biology. 36: 101628. doi:10.1016/j.redox.2020.101628. PMC 7365990. PMID 32863215.
  9. ^ Denisova, T. G.; Denisov, E. T. (May 2009). "Reactivity of natural phenols in radical reactions". Kinetics and Catalysis. 50 (3): 335–343. doi:10.1134/S002315840903001X. ISSN 0023-1584.
  10. ^ Chatgilialoglu, Chryssostomos; Zambonin, Laura; Altieri, Alessio; Ferreri, Carla; Mulazzani, Quinto G; Landi, Laura (December 2002). "Geometrical isomerism of monounsaturated fatty acids: thiyl radical catalysis and influence of antioxidant vitamins". Free Radical Biology and Medicine. 33 (12): 1681–1692. doi:10.1016/S0891-5849(02)01143-7. PMID 12488136.
  11. ^ Tartaro Bujak, Ivana; Mihaljević, Branka; Ferreri, Carla; Chatgilialoglu, Chryssostomos (2016-11-01). "The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid". Free Radical Research. 50 (sup1): S18 – S23. doi:10.1080/10715762.2016.1231401. ISSN 1071-5762. PMID 27776460.
  12. ^ Granold, Matthias; Hajieva, Parvana; Toşa, Monica Ioana; Irimie, Florin-Dan; Moosmann, Bernd (2018-01-02). "Modern diversification of the amino acid repertoire driven by oxygen". Proceedings of the National Academy of Sciences. 115 (1): 41–46. Bibcode:2018PNAS..115...41G. doi:10.1073/pnas.1717100115. ISSN 0027-8424. PMC 5776824. PMID 29259120.
  13. ^ Traber, Maret G.; Atkinson, Jeffrey (July 2007). "Vitamin E, antioxidant and nothing more". Free Radical Biology and Medicine. 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMC 2040110. PMID 17561088.
  14. ^ Ohlow, Maike J.; Granold, Matthias; Schreckenberger, Mathias; Moosmann, Bernd (2012-03-23). "Is the chromanol head group of vitamin E nature's final truth on chain-breaking antioxidants?". FEBS Letters. 586 (6): 711–716. Bibcode:2012FEBSL.586..711O. doi:10.1016/j.febslet.2012.01.022. ISSN 0014-5793. PMID 22281199.
  15. ^ Mortensen, Alan; Skibsted, Leif H.; Sampson, Julia; Rice-Evans, Catherine; Everett, Steven A. (1997-11-24). "Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants". FEBS Letters. 418 (1–2): 91–97. Bibcode:1997FEBSL.418...91M. doi:10.1016/S0014-5793(97)01355-0. ISSN 0014-5793. PMID 9414102.
Stub icon

This organic chemistry article is a stub. You can help Wikipedia by expanding it.