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).<ref>{{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 }} </ref> Thiyl radicals are regularly invoked as intermediates in some biochemical reactions.

==Formation== Thiyl radicals are generated by hydrogen-atom abstraction from thiols. The radical initiator AIBN is proposed to generate thiyl radicals from thiols:<ref>{{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}}</ref> :RN=NR → 2 R^• + N₂ :R^• + R′SH → R′S^• + RH

Thiyl radicals rapidly formation by the action of OH^'''·''' radical (k = 6.8 × 10⁹ M⁻¹s⁻¹) on thiols.<ref name=":0">{{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}}</ref> and decreases through the H^'''·''' radical (k = 6.8 × 10⁹ M⁻¹s⁻¹)<ref name=":0" /> down to peroxyl radicals R-CHOO^'''·''' (k = 4.2 × 10³ M⁻¹s⁻¹).

==Structure== Thiyl radicals have rarely been isolated and purified. Claims of their existence have been often disputed, reflecting their high reactivity.<ref name=Block/>

===Reactions=== The main reaction of thiyl radicals their reversion to disulfides:<ref name=Block>{{cite journal |last1=Sneeden |first1=Eileen Y. |last2=Hackett |first2=Mark J. |last3=Cotelesage |first3=Julien J. H. |last4=Prince |first4=Roger C. |last5=Barney |first5=Monica |last6=Goto |first6=Kei |last7=Block |first7=Eric |last8=Pickering |first8=Ingrid J. |last9=George |first9=Graham N. |title=Photochemically Generated Thiyl Free Radicals Observed by X-ray Absorption Spectroscopy |journal=Journal of the American Chemical Society |date=2017 |volume=139 |issue=33 |pages=11519–11526 |doi=10.1021/jacs.7b05116 |pmid=28750509 |bibcode=2017JAChS.13911519S |osti=1394076 }}</ref> :{{chem2| 2 RS* -> RS\sSR}} Thiyl radicals are intermediates in the thiol-ene reaction, which is the basis of some polymeric coatings and adhesives. Thiyl radicals catalyze diverse reactions involving unsaturated substrates.<ref>{{cite journal|author1=Kosaka, S. |author2=Kurebayashi,K. |author3=Yamato, N. |author4=Tanaka, H. |author5=Haruta, N. |author6=Yamamoto, M.|title= Thiyl Chemistry: Cysteine-Catalyzed Maleate Isomerization via Aqueous Thiyl Radical Processes|journal=Green Chemistry|year=2025|volume=27|issue=10 |pages=2743–2750|doi=10.1039/d4gc06310d }}</ref>

== Thiyl radical in biology == Thiyl radicals in vivo primarily are derived from the amino acid residue cysteine.

Thiyl radicals are involved in the mechanism of action of ribonucleotide reductase, an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides.<ref name="pmid1412696">{{cite journal |last1=Stubbe |first1=Joanne |last2=Nocera |first2=Daniel G. |last3=Yee |first3=Cyril S. |last4=Chang |first4=Michelle C. Y. |title=Radical Initiation in the Class I Ribonucleotide Reductase: Long-Range Proton-Coupled Electron Transfer? |journal=Chemical Reviews |date=2003 |volume=103 |issue=6 |pages=2167–2202 |doi=10.1021/cr020421u |pmid=12797828 }}</ref> It catalyzes this formation by removing the 2'-hydroxyl group of the ribose ring of nucleoside diphosphates (or triphosphates depending on the class of RNR).

Other important substrates of thiyl radicals in biological systems are lipids, where thiyl radicals promote peroxidation.<ref name=":1">{{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 |page=885 |doi=10.3390/antiox11050885 |doi-access=free |issn=2076-3921 |pmc=9137623 |pmid=35624747}}</ref> In this process, thiyl radicals act as chain transfer catalysts by transferring the unpaired electron to a new lipid, thereby.<ref name=":1" /> Other substrates of thiyl radicals include other proteins (k = 1.4 × 10⁵ M⁻¹s⁻¹),<ref>{{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 }}</ref> monounsaturated fatty acids (MUFAs) (k = 1.6 × 10⁵ M⁻¹s⁻¹),<ref>{{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 }}</ref> and ubiquinone (k = 2.5 × 10³ M⁻¹s⁻¹). 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.<ref>{{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 |page=6743 |doi=10.3390/molecules26216743 |doi-access=free |issn=1420-3049 |pmc=8586999 |pmid=34771157}}</ref><ref>{{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 |article-number=101628 |doi=10.1016/j.redox.2020.101628 |pmc=7365990 |pmid=32863215}}</ref>

=== Elimination of thiyl radicals === Phenolic antioxidants, such as ubiquinone or α-tocopherol, are inefficient scavengers of thiyl radicals.<ref name=":1" /><ref>{{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 }}</ref><ref>{{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 }}</ref><ref name=":0"/> 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.<ref>{{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 }}</ref><ref>{{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}}</ref><ref>{{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}}</ref> Isoprenoid polyenes, such as carotenoids like lycopene, react at very high rates with thiyl radicals (up to 10⁹ M⁻¹s⁻¹).<ref>{{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 }}</ref> In aqueous media ascorbic acid and glutathione react rapidly with thiyl radicals (>10⁸ M⁻¹s⁻¹) and are present in high concentrations. Thus, in aqueous environments, thiyl radicals can be effectively neutralized by these antioxidants.

==References== <references />

Category:Free radicals Category:Organosulfur compounds