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.{{cite journal|author1=Dénès, F. |author2=Pichowicz, M. |author3=Povie, G. |author4=Renaud, P. |title=Thiyl Radicals in Organic Synthesis|journal=Chemical Reviews|year=2014|volume=114|issue=5 |pages=2587–2693|doi=10.1021/cr400441m|pmid=24383397 }}
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:{{cite journal|author1=Hoyle, C. E. |author2=Lee, T. Y. |author3=Roper, T. |title=Thiol–enes: Chemistry of the Past with Promise for the Future|journal=Journal of Polymer Science Part A: Polymer Chemistry|year=2004|volume=42|issue=21 |pages=5301–5338|doi=10.1002/pola.20366|bibcode=2004JPoSA..42.5301H |doi-access=free}}
: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){{Cite journal |last1=Tartaro Bujak |first1=Ivana |last2=Mihaljević |first2=Branka |last3=Ferreri |first3=Carla |last4=Chatgilialoglu |first4=Chryssostomos |date=2016-11-01 |title=The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid |url=https://www.tandfonline.com/doi/full/10.1080/10715762.2016.1231401 |journal=Free Radical Research |language=en |volume=50 |issue=sup1 |pages=S18–S23 |doi=10.1080/10715762.2016.1231401 |pmid=27776460 |issn=1071-5762}} and decreases through the H· radical (k = 6.8 x 109 M−1s−1) 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.{{Cite journal |last1=Moosmann |first1=Bernd |last2=Hajieva |first2=Parvana |date=2022-04-29 |title=Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge |journal=Antioxidants |language=en |volume=11 |issue=5 |pages=885 |doi=10.3390/antiox11050885 |doi-access=free |issn=2076-3921 |pmc=9137623 |pmid=35624747}} In this process, thiyl radicals act as chain transfer catalysts by transferring the unpaired electron to a new lipid, thereby accelerating lipid peroxidation. Other substrates of thiyl radicals include other proteins (k = 1.4 x 105 M−1s−1),{{Cite journal |last1=Nauser |first1=Thomas |last2=Pelling |first2=Jill |last3=Schöneich |first3=Christian |date=2004-10-01 |title=Thiyl Radical Reaction with Amino Acid Side Chains: Rate Constants for Hydrogen Transfer and Relevance for Posttranslational Protein Modification |url=https://pubs.acs.org/doi/10.1021/tx049856y |journal=Chemical Research in Toxicology |language=en |volume=17 |issue=10 |pages=1323–1328 |doi=10.1021/tx049856y |issn=0893-228X|url-access=subscription }} monounsaturated fatty acids (MUFAs) (k = 1.6 x 105 M−1s−1),{{Cite journal |last1=Chatgilialoglu |first1=Chryssostomos |last2=Ferreri |first2=Carla |date=2005-06-01 |title=Trans Lipids: The Free Radical Path |url=https://pubs.acs.org/doi/10.1021/ar0400847 |journal=Accounts of Chemical Research |language=en |volume=38 |issue=6 |pages=441–448 |doi=10.1021/ar0400847 |pmid=15966710 |issn=0001-4842|url-access=subscription }} 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, caused damage to membrane proteins and was associated with a decline in polyunsaturated fatty acids (PUFAs) and a shortened lifespan.{{Cite journal |last1=Heymans |first1=Victoria |last2=Kunath |first2=Sascha |last3=Hajieva |first3=Parvana |last4=Moosmann |first4=Bernd |date=2021-11-08 |title=Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs |journal=Molecules |language=en |volume=26 |issue=21 |pages=6743 |doi=10.3390/molecules26216743 |doi-access=free |issn=1420-3049 |pmc=8586999 |pmid=34771157}}{{Cite journal |last1=Kunath |first1=Sascha |last2=Schindeldecker |first2=Mario |last3=De Giacomo |first3=Antonio |last4=Meyer |first4=Theresa |last5=Sohre |first5=Selina |last6=Hajieva |first6=Parvana |last7=von Schacky |first7=Clemens |last8=Urban |first8=Joachim |last9=Moosmann |first9=Bernd |date=September 2020 |title=Prooxidative chain transfer activity by thiol groups in biological systems |journal=Redox Biology |language=en |volume=36 |pages=101628 |doi=10.1016/j.redox.2020.101628 |pmc=7365990 |pmid=32863215}}
= Elimination of Thiyl Radicals =
The most important phenolic antioxidants, such as ubiquinone or α-tocopherol, are inefficient scavengers of thiyl radicals. Both substances are not sufficiently reactive,{{Cite journal |last1=Denisova |first1=T. G. |last2=Denisov |first2=E. T. |date=May 2009 |title=Reactivity of natural phenols in radical reactions |url=http://link.springer.com/10.1134/S002315840903001X |journal=Kinetics and Catalysis |language=en |volume=50 |issue=3 |pages=335–343 |doi=10.1134/S002315840903001X |issn=0023-1584|url-access=subscription }}{{Cite journal |last1=Chatgilialoglu |first1=Chryssostomos |last2=Zambonin |first2=Laura |last3=Altieri |first3=Alessio |last4=Ferreri |first4=Carla |last5=Mulazzani |first5=Quinto G |last6=Landi |first6=Laura |date=December 2002 |title=Geometrical isomerism of monounsaturated fatty acids: thiyl radical catalysis and influence of antioxidant vitamins |url=https://linkinghub.elsevier.com/retrieve/pii/S0891584902011437 |journal=Free Radical Biology and Medicine |language=en |volume=33 |issue=12 |pages=1681–1692 |doi=10.1016/S0891-5849(02)01143-7|pmid=12488136 |url-access=subscription }} 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.{{Cite journal |last1=Granold |first1=Matthias |last2=Hajieva |first2=Parvana |last3=Toşa |first3=Monica Ioana |last4=Irimie |first4=Florin-Dan |last5=Moosmann |first5=Bernd |date=2018-01-02 |title=Modern diversification of the amino acid repertoire driven by oxygen |journal=Proceedings of the National Academy of Sciences |language=en |volume=115 |issue=1 |pages=41–46 |doi=10.1073/pnas.1717100115 |doi-access=free |issn=0027-8424 |pmc=5776824 |pmid=29259120|bibcode=2018PNAS..115...41G }}{{Cite journal |last1=Traber |first1=Maret G. |last2=Atkinson |first2=Jeffrey |date=July 2007 |title=Vitamin E, antioxidant and nothing more |journal=Free Radical Biology and Medicine |language=en |volume=43 |issue=1 |pages=4–15 |doi=10.1016/j.freeradbiomed.2007.03.024 |pmc=2040110 |pmid=17561088}}{{Cite journal |last1=Ohlow |first1=Maike J. |last2=Granold |first2=Matthias |last3=Schreckenberger |first3=Mathias |last4=Moosmann |first4=Bernd |date=2012-03-23 |title=Is the chromanol head group of vitamin E nature's final truth on chain-breaking antioxidants? |url=https://febs.onlinelibrary.wiley.com/doi/10.1016/j.febslet.2012.01.022 |journal=FEBS Letters |language=en |volume=586 |issue=6 |pages=711–716 |doi=10.1016/j.febslet.2012.01.022 |pmid=22281199 |bibcode=2012FEBSL.586..711O |issn=0014-5793}} Isoprenoid polyenes, such as carotenoids like lycopene, exhibit very high rate constants regarding thiyl radicals (up to 109 M−1s−1).{{Cite journal |last1=Mortensen |first1=Alan |last2=Skibsted |first2=Leif H. |last3=Sampson |first3=Julia |last4=Rice-Evans |first4=Catherine |last5=Everett |first5=Steven A. |date=1997-11-24 |title=Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants |url=https://febs.onlinelibrary.wiley.com/doi/10.1016/S0014-5793%2897%2901355-0 |journal=FEBS Letters |language=en |volume=418 |issue=1–2 |pages=91–97 |doi=10.1016/S0014-5793(97)01355-0 |pmid=9414102 |bibcode=1997FEBSL.418...91M |issn=0014-5793|url-access=subscription }} However, even with supplementation, the effect of lycopene is not sufficient to adequately counteract lipid peroxidation. 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.