View source for Radical (chemistry)

{{short description|Atom, molecule, or ion that has an unpaired valence electron; typically highly reactive}}
{{Redirect|Free radical|the aging theory|Free-radical theory of aging|other uses|Free radical (disambiguation)}}
{{about|free radicals|radicals within larger molecules|Moiety (chemistry)}}
[[File:Hydroxyl radical.svg|thumb|upright=0.5|The [[hydroxyl radical]], [[Lewis structure]] shown, contains one unpaired electron.]]
[[File:Hydroxide vs hydroxyl.svg|thumb| [[Lewis dot structure]] of a [[Hydroxide]] ion compared to a [[hydroxyl radical]]]]
In [[chemistry]], a '''radical''', also known as a '''free radical''', is an [[atom]], [[molecule]], or [[ion]] that has at least one [[unpaired electron|unpaired valence electron]].<ref>IUPAC Gold Book [http://goldbook.iupac.org/R05066.html ''radical (free radical)''] [http://www.iupac.org/goldbook/R05066.pdf PDF] {{Webarchive|url=https://web.archive.org/web/20170302220258/http://goldbook.iupac.org/R05066.html |date=2017-03-02}}</ref><ref>{{Cite journal |last=Hayyan |first=M. |last2=Hashim |first2=M.A. |last3=Anjkut |first3=I.M. |year=2016 |title=Superoxide Ion: Generation and Chemical Implications |journal=Chem. Rev. |volume=116 |issue=5 |pages=3029–85 |doi=10.1021/acs.chemrev.5b00407 |pmid=26875845 |doi-access=free}}</ref>
With some exceptions, these unpaired electrons make radicals highly [[chemical reaction|chemically reactive]]. Many radicals spontaneously [[dimer (chemistry)|dimerize]]. Most organic radicals have short lifetimes.

A notable example of a radical is the [[hydroxyl radical]] (HO'''·'''), a molecule that has one unpaired electron on the oxygen atom. Two other examples are [[triplet oxygen]] and [[methylene radical|triplet carbene]] ('''꞉'''{{chem|CH|2}}) which have two unpaired electrons.

Radicals may be generated in a number of ways, but typical methods involve [[redox reaction]]s. [[Ionizing radiation]], heat, electrical discharges, and [[electrolysis]] are known to produce radicals. Radicals are intermediates in many chemical reactions, more so than is apparent from the balanced equations. 

Radicals are important in [[combustion]], [[atmospheric chemistry]], [[polymerization]], [[Plasma (physics)|plasma]] chemistry, [[biochemistry]], and many other chemical processes. A majority of natural products are generated by radical-generating enzymes. In living organisms, the radicals [[superoxide]] and [[nitric oxide]] and their reaction products regulate many processes, such as control of vascular tone and thus blood pressure. They also play a key role in the intermediary metabolism of various biological compounds. Such radicals can even be messengers in a process dubbed [[redox signaling]]. A radical may be trapped within a [[Cage effect (chemistry)|solvent cage]] or be otherwise bound.

== Formation ==
Radicals are either (1) formed from spin-paired molecules or (2) from other radicals. Radicals are formed from spin-paired molecules through [[Homolysis (chemistry)|homolysis]] of weak bonds or electron transfer, also known as reduction. Radicals are formed from other radicals through substitution, [[addition]], and elimination reactions.

===Radical formation from spin-paired molecules===

====Homolysis====
[[File:Bromine homolysis.svg|thumb|Homolysis of a bromine molecule producing two bromine radicals]]
[[Homolysis (chemistry)|Homolysis]] makes two new radicals from a spin-paired molecule by breaking a covalent bond, leaving each of the fragments with one of the electrons in the bond.<ref name=":1" /> The homolytic [[Bond dissociation energy|bond dissociation energies]], usually abbreviated as "Δ''H''{{px1}}°" are a measure of bond strength. Splitting H<sub>2</sub> into 2&nbsp;H<sup>•</sup>, for example, requires a Δ''H''{{px1}}° of +435 [[Joule per mole|kJ/mol]], while splitting Cl<sub>2</sub> into two Cl<sup>•</sup> requires a Δ''H''{{px1}}° of +243 kJ/mol. For weak bonds, homolysis can be induced thermally. Strong bonds require high energy photons or even flames to induce homolysis.{{cn|date=February 2025}}

Some homolysis reactions are particularly important because they serve as an initiator for other radical reactions. One such example is the homolysis of halogens, which occurs under light and serves as the driving force for radical halogenation reactions.  Another notable reaction is the homolysis of dibenzoyl peroxide, which results in the formation of two benzoyloxy radicals and acts as an initiator for many radical reactions.<ref>{{Cite web |title=Diacyl Peroxides |url=https://polymerdatabase.com/polymer%20chemistry/Diaroyl%20Peroxides.html |access-date=2020-12-08 |website=polymerdatabase.com}}</ref>
[[File:Homolysis2.svg|thumb|center|upright=1.95|Homolysis of dibenzoyl peroxide producing two benzoyloxy radicals]]

====Reduction====
<!--[[Single-electron transfer]] and [[Single electron transfer]] redirect here-->
[[File: Lithium Naphthalenide.jpg|thumb|left|The deep colour of [[lithium naphthalene]] results from the lithium naphthanide radical.|120px]]
Classically, radicals form by one-electron [[redox|reduction]]s. Typically one-electron reduced organic compounds are unstable. Stability is conferred to the radical anion when the charge can be [[delocalization|delocalized]]. Examples include alkali metal [[lithium naphthalene|naphthenide]]s, [[anthracene|anthracenide]]s, and [[ketyl]]s.

===Radical formation from other radicals===

====Abstraction====
[[File:Abstraction.svg|thumb|upright=1.95|Radical abstraction between a benzoyloxy radical and hydrogen bromide]]
[[Hydrogen atom abstraction|Hydrogen abstraction]] generates radicals. To achieve this reaction, the C-H bond of the H-atom donor must be weak, which is rarely the case in organic compounds. [[Allylic]] and especiall doubly allylic C-H bonds are prone to abstraction by O<sub>2</sub>. This reaction is the basis of [[drying oil]]s, such as [[linoleic acid]] derivatives.

====Addition====
[[File:radicaladdition.svg|thumb|upright=1.15|Radical addition of a bromine radical to a substituted alkene]]
In [[free-radical addition]]s, a radical adds to a spin-paired substrate. When applied to organic compounds, the reaction usually entails addition to an alkene. This addition generates a new radical, which can add to yet another alkene, etc. This behavior underpins [[radical polymerization]], technology that produces many [[plastic]]s.<ref>{{Cite journal |last=Gridnev |first=Alexei A. |last2=Ittel |first2=Steven D. |date=2001 |title=Catalytic Chain Transfer in Free-Radical Polymerizations |journal=Chemical Reviews |volume=101 |issue=12 |pages=3611–3660 |doi=10.1021/cr9901236 |pmid=11740917}}</ref><ref>{{Cite journal |last=Monroe |first=Bruce M. |last2=Weed |first2=Gregory C. |date=1993 |title=Photoinitiators for free-radical-initiated photoimaging systems |journal=Chemical Reviews |volume=93 |pages=435–448 |doi=10.1021/cr00017a019}}</ref>

====Elimination====
Radical elimination can be viewed as the reverse of radical addition. In radical elimination, an unstable radical compound breaks down into a spin-paired molecule and a new radical compound. Shown below is an example of a radical elimination reaction, where a benzoyloxy radical breaks down into a phenyl radical and a carbon dioxide molecule.<ref>{{Citation |last=Su |first=Wei-Fang |title=Radical Chain Polymerization |date=2013 |work=Principles of Polymer Design and Synthesis |volume=82 |pages=137–183 |editor-last=Su |editor-first=Wei-Fang |series=Lecture Notes in Chemistry |place=Berlin, Heidelberg |publisher=Springer |language=en |doi=10.1007/978-3-642-38730-2_7 |isbn=978-3-642-38730-2 |doi-access=free}}</ref>

[[File:radicalelimination.svg|thumb|upright=1.75|A radical elimination reaction of a benzoyloxy radical|center]]

== Stability==
A large variety of inorganic radicals, as well as a smaller number of organic radicals, are stable and in fact isolable.  [[Nitric oxide]] (NO) is well known example of an isolable inorganic radical, and [[Fremy's salt]] (Potassium nitrosodisulfonate, (KSO<sub>3</sub>)<sub>2</sub>NO) is a related example. Many [[sulfur mononitride|thiazyl]] radicals are known, despite limited π [[resonance stabilization]] (see below).<ref>{{Cite book |last=Oakley |first=Richard T. |title=Progress in Inorganic Chemistry |year=1988 |isbn=978-0-470-16637-6 |volume=36 |pages=299–391 |chapter=Cyclic and Heterocyclic Thiazenes |doi=10.1002/9780470166376.ch4 |access-date=2011-03-31 |chapter-url=http://www.chembio.uoguelph.ca/oakley/papers/rto_086.pdf |archive-url=https://web.archive.org/web/20150923202507/http://www.chembio.uoguelph.ca/oakley/papers/rto_086.pdf |archive-date=2015-09-23 |url-status=dead |department=Cyclic and Heterocyclic Thiazenes (section)}}</ref><ref>{{Cite book |last=Rawson |first=J |title=The Chemistry of Dithiadiazolylium and Dithiadiazolyl Rings**Dedicated to Dr. Z. V. Hauptman, in appreciation of his important contribution to sulfur-nitrogen and carbon-sulfur-nitrogen chemistry |last2=Banister |first2=A |last3=Lavender |first3=I |year=1995 |isbn=978-0-12-020762-6 |series=Advances in Heterocyclic Chemistry |volume=62 |pages=137–247 |doi=10.1016/S0065-2725(08)60422-5}}</ref>

The term "stable radical" bears a pernicious ambiguity.  Radicals' behavior varies with distinct thermodynamic and kinetic stabilities, and no general rule connects the two.  For example, [[resonance (chemistry)|resonance delocalization]] thermodynamically stabilizes [[benzylic|benzyl]] radicals, but those radicals undergo rapid, [[diffusion]]-limited dimerization.  Under normal conditions, their kinetic lifetime [[nanosecond#Common measurements|measures in nanoseconds]]<!--Weirdly, more examples there than in [[Orders of magnitude (time)]]-->.<ref name=GITerms/>  Conversely, H<sup>•</sup> is highly reactive (thermodynamically unstable), but also the [[elemental abundance#Universe|most abundant chemical in the universe]] (kinetically stable) [[collision theory|because]] it exists primarily in low-density environments.{{cn|date=February 2025}}  

Following Griller and Ingold's extremely influential 1976 review,<ref name=GITerms>{{Cite journal |last=Griller |first=David |last2=Ingold |first2=Keith U. |year=1976 |title=Persistent carbon-centered radicals |journal=Accounts of Chemical Research |volume=9 |pages=13–19 |doi=10.1021/ar50097a003}}</ref> modern chemists call a carbon-centered radical R<sup>•</sup> ''stabilized'' if the corresponding R&ndash;H bond is [[bond energy|weaker]] than in an [[alkane]]; the radical is ''persistent'' if the radical lifetime lasts longer than the encounter limit.{{sfn|Hicks|2010|p=231}}  Persistence is almost exclusively a steric effect.<ref name=GITerms/>  However, orbitals of high [[angular momentum quantum number|angular momentum]] (''d'' or ''f''), delocalization, and the [[α effect]] can all make organic radicals stabilized. 

[[image:2,2,6,6-Tetramethylpiperidinyloxyl.svg|thumb|left|upright=1.1|[[TEMPO|2,2,6,6-Tetramethylpiperidinyloxyl]] is a robust organic radical.]]
The radical of commerce [[TEMPO|2,2,6,6-tetramethylpiperidinyloxyl (TEMPO)]] illustrates these phenomena: the [[methyl]] substituents shield the [[N-Hydroxypiperidine|''N''-hydroxypiperidinyl]] core radical for persistence; and the [[vicinal (chemistry)|vicinal]] nitrogen and oxygen lone pairs weaken any bonds that might form to oxygen, keeping the radical stabilized.  Consequently TEMPO behaves, aside from its [[paramagnetism]], like a normal organic compound.<ref name=":1"/>{{bcn|date=February 2025}}  

=== Singly-occupied molecular orbitals ===
[[File:Electron-Donating Diagram.svg|thumb|upright=1.3|Molecular orbital diagram of a radical with an electron-donating group]]
[[File:Electron-Withdrawing Diagram.svg|thumb|upright=1.3|Molecular orbital diagram of a radical with an electron-withdrawing group]]
In [[molecular orbital theory]], a radical electronic structure is characterized by a [[HOMO|highest-energy filled molecular orbital]] that contains only an unpaired electron.  That orbital is called the "singly-occupied molecular orbital" or SOMO, and is traditionally filled spin-up [[without loss of generality]].<ref name=":1"/>{{rp|p=977}}  Radical compounds are thermodynamically unstable because [[Born-Oppenheimer approximation|fixed nuclear positions]] cannot simultaneously minimize the filled [[spin (physics)#Direction|spin-up]] orbital energies (which include the SOMO) and the filled spin-down orbital energies (which do not).  Thus a SOMO whose energy depends little on nuclear position can produce a relatively stabilized radical.{{cn|date=February 2025}}<!--Maybe a solid-state physics text?  This is similar, but not identical, to [[Marcus theory]]-->  Two common types of such SOMOs are a ''d'' orbital,<ref>{{cite journal|doi=10.1021/cr020406p|journal=Chemical Reviews|year=2003|volume=103|p=789|title=Persistent and stable radicals of the heavier main group elements and related species|first=Philip&nbsp;P.|last=Power|orig-date=19 July 2002|publisher=American Chemical Society}}</ref> which requires only [[Jahn-Teller distortion]];{{cn|date=February 2025}} and a SOMO delocalized over a large portion of the molecule or crystal,<ref name=CSA>{{cite book|first1=Francis&nbsp;A.|last1=Carey|first2=Richard&nbsp;J.|last2=Sundberg|title=Advanced Organic Chemistry|edition=2|volume=A: Structures and Mechanisms|publisher=Plenum|location=New York|year=1984|lccn=84-8229|isbn=0-306-41087-7}}</ref>{{rp|pp=649-650}} which requires little motion at each nucleus.{{cn|date=February 2025}}<!--Probably same as previous src, whatever that is-->  

SOMOs can in principle be of any type, but amongst the [[main group]] atoms, almost all known stable radicals have a [[π bond|π-type]] SOMO.{{Sfn|Hicks|2011|p=231}}  Consequently SOMOs delocalize like other π bonds: to nearby [[lone pair]]s on [[alcohol (chemistry)|hydroxyl groups]] (−OH), [[ethers]] (−OR), or [[amines]] (−NH<sub>2</sub> or −NR); to [[conjugated system|conjugated π bonds]] in [[alkene]]s, [[carbonyl]]s, or [[nitrile]]s; or in [[hyperconjugation]] to nearby [[hydrogen]]- or [[fluorine]]-rich moieties.<!--People don't usually think of trifluoromethyl electron withdrawal as hyperconjugation, but it is!--><ref>{{harvnb|Carey|Sundberg|1984}}, pp.&nbsp;649&ndash;650.  As {{wikicite|Smith (2023), ''March's Organic Chemistry'' (8<sup>th</sup>&nbsp;ed.) pp.&nbsp;254,&nbsp;256|ref={{harvid|Smith|2023}}}} notes, a contrary view is suggested in 
* Gronert, S. (2006) in ''J. Org. Chem.'', vol.&nbsp;71, pp.&nbsp;7045&ndash;;
* &mdash;&mdash;&mdash; (2007) in ''Org. Lett.'', vol.&nbsp;9, pp.&nbsp;2211&ndash;; and 
* Galli, C.; Guarnieri, A.; Koch, H.; Mencarelli, P.; and Rappoport, Z. (1997) ''J. Org. Chem.'', vol.&nbsp;62, pp.&nbsp;4072&ndash;.
</ref>  [[File:radical hyperconjugation.svg|thumb|center|upright=1.6|The relative stabilities of tertiary, secondary, primary and methyl radicals can be explained by hyperconjugation]]  Many of the above [[functional group]]s are [[electron-donating]], but electron donation is not necessary to achieve SOMO delocalization, and electron withdrawal functions just as well.<ref name=":1">{{Cite book |last=Clayden, Jonathan |url=https://www.worldcat.org/oclc/761379371 |title=Organic chemistry |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart G. |date=2012 |publisher=Oxford University Press |isbn=978-0-19-927029-3 |edition=2nd |location=Oxford |oclc=761379371}}</ref>{{rp|978}}  Indeed, radicals are particularly stable if they can delocalize into both an electron-withdrawing and an electron-donating group, the "[[capto-dative effect]]".<ref>{{harvnb|Carey|Sundberg|1984}}, p.&nbsp;651.  {{harvnb|Smith|2023}}, p.&nbsp;256 writes: "There is some evidence in favor of the captodative effect, some of it from [[Electron spin resonance|ESR]] studies. However, there is also experimental and theoretical evidence against it," with extensive citations on both sides.</ref>

In the electron-donating case, the SOMO interacts with the lower energy lone pair to form a new, lower-energy, filled, delocalized bond orbital and a new, higher-energy antibonding SOMO (in net, a [[three-electron bond]]).  Because the new bonding orbital contains more electrons than the SOMO, the resulting electronic state reduces molecular energy.<ref name=":1"/>{{rp|979}}  

In the electron-withdrawing case, the SOMO interacts with an empty σ* or π* antibonding orbital.  That antibonding orbital has less energy than the isolated SOMO, as does the resulting [[hybrid orbital]].<ref name=":1"/>{{rp|978}}

=== Common equilibria ===
[[File:Vitamin E radical.svg |thumb|upright=1.5|The radical derived from ''[[tocopherol|α-tocopherol]]'']]
The stability of many (or most) organic radicals is not indicated by their isolability but is manifested in their ability to function as donors of H<sup>•</sup>. This property reflects a weakened bond to hydrogen, usually O−H but sometimes N−H or C−H. This behavior is important because these H<sup>•</sup> donors serve as antioxidants in biology and in commerce. Illustrative is [[tocopherol|α-tocopherol]] ([[vitamin E]]). The tocopherol radical itself is insufficiently stable for isolation, but the parent molecule is a highly effective hydrogen-atom donor. The C−H bond is weakened in [[triphenylmethyl]] (trityl) derivatives.{{cn|date=February 2025}}

Most main-group radicals are in notional equilibrium with [[closed-shell]] dimers.  For example, [[nitrogen dioxide]] equilibrates with [[dinitrogen tetroxide]], and [[tributyltin]] radicals equilibrate with {{ill|hexabutyldistannane|de|Hexabutyldistannan}}.  Consequently radicals may be stabilized when the [[dimer (chemistry)|dimeric]] bond is weak.  For example, compounds with a radical localized to atoms with adjacent lone pairs experience a powerful α effect when dimerized, such that the dimer may practically never form.<ref name=HicksColl>{{cite book|pp=317-318|title=Stable Radicals|editor-first=Robin&nbsp;G.|editor-last=Hicks|publisher=Wiley|year=2010|isbn=978-0-470-77083-2}}</ref>  Likewise, the [[quinone|quinonic]] loss of aromaticity in [[Gomberg's dimer]] predisposes the compound towards homolysis.

In other cases, radical dimers may form a "[[π dimer]]", analogous to a [[donor-acceptor complex]] but without charge transfer.<ref>{{cite journal|url=https://pubs.rsc.org/en/content/articlepdf/2007/ob/b617142g|title=What's new in stable radical chemistry?|first=Robin&nbsp;G.|last=Hicks|orig-date=23 Nov 2006|date=30 Mar 2007|doi=10.1039/b617142g|journal=Organic & Biomolecular Chemistry|publisher=The Royal Society of Chemistry|volume=5|pp=1324-1328,1331-1335}}</ref><!--TBH probably a better src than that-->

==Diradicals==
[[Diradical]]s are molecules containing two radical centers. [[Dioxygen]] (O<sub>2</sub>) is an important example of a stable diradical. [[Singlet oxygen]], the lowest-energy non-radical state of dioxygen, is less stable than the diradical due to [[Hund's rule of maximum multiplicity]]. The relative stability of the oxygen diradical is primarily due to the [[Quantum chemistry|spin-forbidden]] nature of the triplet-singlet transition required for it to grab electrons, i.e., "'''oxidize'''". The diradical state of oxygen also results in its paramagnetic character, which is demonstrated by its attraction to an external magnet.<ref>However, [[paramagnetism]] does not necessarily imply radical character.{{cn|date=February 2025}}</ref> Diradicals can also occur in [[Transition metal oxo complex|metal-oxo complexes]], lending themselves for studies of [[spin forbidden reactions]] in [[transition metal]] chemistry.<ref>{{Cite journal |last=Linde |first=C. |last2=Åkermark |first2=B. |last3=Norrby |first3=P.-O. |last4=Svensson |first4=M. |date=1999 |title=Timing is Critical: Effect of Spin Changes on the Diastereoselectivity in Mn(Salen)-Catalyzed Epoxidation |journal=Journal of the American Chemical Society |volume=121 |issue=21 |pages=5083–84 |doi=10.1021/ja9809915}}</ref> [[Carbene]]s in their triplet state can be viewed as diradicals centred on the same atom, while these are usually highly reactive [[persistent carbene]]s are known, with N-heterocyclic carbenes being the most common example.

Triplet [[carbene]]s and [[nitrene]]s are diradicals. Their chemical properties are distinct from the properties of their singlet analogues.

==Occurrence of radicals==
===Combustion===
[[File:Spectrum of blue flame.png|thumb|upright=1.5|Spectrum of the blue flame from a [[butane]] torch showing excited molecular radical band emission and [[Swan bands]]]]
{{main|Combustion#Reaction mechanism}}
A familiar radical reaction is [[combustion]]. The [[oxygen]] molecule is a stable [[diradical]], best represented by <sup>•</sup>O–O<sup>•</sup>. Because [[Spin (physics)|spins]] of the electrons are parallel, this molecule is stable. While the [[ground state]] of oxygen is this unreactive spin-unpaired ([[Triplet oxygen|triplet]]) diradical, an extremely reactive spin-paired ([[Singlet oxygen|singlet]]) state is available. For combustion to occur, the [[energy barrier]] between these must be overcome. This barrier can be overcome by heat, requiring high temperatures. The triplet-singlet transition is also "[[Forbidden mechanism|forbidden]]". This presents an additional barrier to the reaction. It also means molecular oxygen is relatively unreactive at room temperature except in the presence of a catalytic heavy atom such as iron or copper.

Combustion consists of various radical chain reactions that the singlet radical can initiate. The [[flammability]] of a given material strongly depends on the concentration of radicals that must be obtained before initiation and propagation reactions dominate leading to [[combustion]] of the material. Once the combustible material has been consumed, termination reactions again dominate and the flame dies out. As indicated, promotion of propagation or termination reactions alters flammability. For example, because lead itself deactivates radicals in the gasoline-air mixture, [[tetraethyl lead]] was once commonly added to gasoline. This prevents the combustion from initiating in an uncontrolled manner or in unburnt residues ([[engine knocking]]) or premature ignition ([[preignition]]).

When a hydrocarbon is burned, a large number of different oxygen radicals are involved. Initially, [[hydroperoxyl|hydroperoxyl radical]] (HOO<sup>•</sup>) are formed. These then react further to give [[organic hydroperoxide]]s that break up into [[hydroxyl radical]]s (HO<sup>•</sup>).

===Polymerization===
Many [[polymerization]] reactions are initiated by radicals. Polymerization involves an initial radical adding to non-radical (usually an alkene) to give new radicals. This process is the basis of the [[radical chain reaction]]. The art of polymerization entails the method by which the initiating radical is introduced. For example, [[methyl methacrylate]] (MMA) can be polymerized to produce [[Poly(methyl methacrylate)]] (PMMA – Plexiglas or Perspex) via a repeating series of [[Free-radical addition|radical addition]] steps:
[[image:PMMA-Wachstum.svg|upright=3.35|center|thumb|Radical intermediates in the formation of polymethacrylate (plexiglas or perspex)]]

Newer radical polymerization methods are known as [[living polymerization|living radical polymerization]]. Variants include reversible addition-fragmentation chain transfer ([[RAFT (chemistry)|RAFT]]) and atom transfer radical polymerization ([[ATRP (chemistry)|ATRP]]).

Being a prevalent radical, O<sub>2</sub> reacts with many organic compounds to generate radicals together with the [[hydroperoxide]] radical. [[Drying oil]]s and alkyd paints harden due to radical crosslinking initiated by oxygen from the atmosphere.

===Atmospheric radicals===
{{See also|Oxygen cycle|Ozone-oxygen cycle}}
The most common radical in the lower atmosphere is molecular dioxygen. [[Photodissociation]] of source molecules produces other radicals. In the lower atmosphere, important radical are produced by the photodissociation of [[nitrogen dioxide]] to an oxygen atom and [[nitric oxide]] (see {{EquationNote|eq. 1.1}} below), which plays a key role in [[Photochemical smog|smog]] formation—and the photodissociation of ozone to give the excited oxygen atom O(1D) (see {{EquationNote|eq. 1.2}} below). The net and return reactions are also shown ({{EquationNote|eq. 1.3}} and {{EquationNote|eq. 1.4}}, respectively).
{{NumBlk|:|<chem>NO2 ->[h \nu] NO + O</chem>|{{EquationRef|eq. 1.1}}}}
{{NumBlk|:|<chem>O + O2 -> O3</chem>|{{EquationRef|eq. 1.2}}}}
{{NumBlk|:|<chem>NO2 + O2 ->[h \nu] NO + O3</chem>|{{EquationRef|eq. 1.3}}}}
{{NumBlk|:|<chem>NO + O3 -> NO2 + O2</chem>|{{EquationRef|eq. 1.4}}}}
In the upper atmosphere, the photodissociation of normally unreactive [[chlorofluorocarbon]]s (CFCs) by solar [[ultraviolet radiation]] is an important source of radicals (see eq. 1 below). These reactions give the [[chlorine]] radical, Cl<sup>•</sup>, which catalyzes the conversion of [[ozone]] to O<sub>2</sub>, thus facilitating [[ozone depletion]] ({{EquationNote|eq. 2.2}}–{{EquationNote|eq. 2.4}} below).
{{NumBlk|:|<chem>CFCS ->[h \nu] Cl^\bullet</chem>|{{EquationRef|eq. 2.1}}}}
{{NumBlk|:|<chem>Cl^\bullet {}+ O3 -> ClO^\bullet {}+ O2</chem>|{{EquationRef|eq. 2.2}}}}
{{NumBlk|:|<chem>O3 ->[h \nu] O + O2</chem>|{{EquationRef|eq. 2.3}}}}
{{NumBlk|:|<chem>O {}+ ClO^\bullet -> Cl^\bullet {}+ O2</chem>|{{EquationRef|eq. 2.4}}}}
{{NumBlk|:|<chem>2O3 ->[h \nu] 3O2</chem>|{{EquationRef|eq. 2.5}}}}
Such reactions cause the depletion of the [[ozone layer]], especially since the chlorine radical is free to engage in another reaction chain; consequently, the use of chlorofluorocarbons as [[refrigerant]]s has been restricted.

===In biology===
{{See also|Dioxygen in biological reactions}}
[[File:DeoxyadenosylRadical.png|thumb|Structure of the [[deoxyadenosyl radical]], a common biosynthetic intermediate<ref>{{Cite journal |last=Broderick, J.B. |last2=Duffus, B.R. |last3=Duschene, K.S. |last4=Shepard, E.M. |year=2014 |title=Radical S-Adenosylmethionine Enzymes |journal=Chemical Reviews |volume=114 |issue=8 |pages=4229–317 |doi=10.1021/cr4004709 |pmc=4002137 |pmid=24476342}}</ref>]]
[[Image:Lignin structure.svg|thumb|upright=2.25|An approximate structure of [[lignin]], which constitutes about 30% of plant matter. It is formed by radical reactions.]]
Radicals play important roles in biology. Many of these are necessary for life, such as the intracellular killing of bacteria by phagocytic cells such as [[granulocyte]]s and [[macrophage]]s. Radicals are involved in [[signal transduction|cell signalling]] processes,<ref>{{Cite journal |vauthors=Pacher P, Beckman JS, Liaudet L |year=2007 |title=Nitric oxide and peroxynitrite in health and disease |journal=Physiol. Rev. |volume=87 |issue=1 |pages=315–424 |doi=10.1152/physrev.00029.2006 |pmc=2248324 |pmid=17237348}}</ref> known as [[redox signaling]]. For example, radical attack of [[linoleic acid]] produces a series of [[13-hydroxyoctadecadienoic acid]]s and [[9-hydroxyoctadecadienoic acid]]s, which may act to regulate localized tissue inflammatory and/or healing responses, pain perception, and the proliferation of malignant cells. Radical attacks on arachidonic acid and docosahexaenoic acid produce a similar but broader array of signaling products.<ref>{{Cite journal |last=Njie-Mbye |first=Ya Fatou |last2=Kulkarni-Chitnis |first2=Madhura |last3=Opere |first3=Catherine A. |last4=Barrett |first4=Aaron |last5=Ohia |first5=Sunny E. |year=2013 |title=Lipid peroxidation: pathophysiological and pharmacological implications in the eye |journal=Frontiers in Physiology |volume=4 |pages=366 |doi=10.3389/fphys.2013.00366 |pmc=3863722 |pmid=24379787 |doi-access=free}}</ref>

Radicals may also be involved in [[Parkinson's disease]], senile and drug-induced [[deafness]], [[schizophrenia]], and [[Alzheimer's]].<ref>{{Cite journal |last=Floyd |first=R.A. |year=1999 |title=Neuroinflammatory processes are important in neurodegenerative diseases: An hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development |journal=Free Radical Biology and Medicine |volume=26 |issue=9–10 |pages=1346–55 |doi=10.1016/s0891-5849(98)00293-7 |pmid=10381209}}</ref> The classic free-radical syndrome, the iron-storage disease [[hemochromatosis]], is typically associated with a constellation of free-radical-related symptoms including movement disorder, psychosis, skin pigmentary [[melanin]] abnormalities, deafness, arthritis, and diabetes mellitus. The [[free-radical theory]] of aging proposes that radicals underlie the [[Senescence|aging process]] itself. Similarly, the process of mito[[hormesis]] suggests that repeated exposure to radicals may extend life span.

Because radicals are necessary for life, the body has a number of mechanisms to minimize radical-induced damage and to repair damage that occurs, such as the [[enzyme]]s [[superoxide dismutase]], [[catalase]], [[glutathione peroxidase]] and [[glutathione reductase]]. In addition, [[antioxidant]]s play a key role in these defense mechanisms. These are often the three vitamins, [[vitamin A]], [[vitamin C]] and [[vitamin E]] and [[polyphenol antioxidant]]s. Furthermore, there is good evidence indicating that [[bilirubin]] and [[uric acid]] can act as antioxidants to help neutralize certain radicals. Bilirubin comes from the breakdown of [[red blood cell]]s' contents, while uric acid is a breakdown product of [[purine]]s. Too much bilirubin, though, can lead to [[jaundice]], which could eventually damage the central nervous system, while too much uric acid causes [[gout]].<ref>An overview of the role of radicals in biology and of the use of electron spin resonance in their detection may be found in {{Cite book |last=Rhodes C.J. |title=Toxicology of the Human Environment – the critical role of free radicals |publisher=Taylor and Francis |year=2000 |isbn=978-0-7484-0916-7 |location=London}}</ref>

===Reactive oxygen species===
[[Reactive oxygen species]] or ROS are species such as [[superoxide]], [[hydrogen peroxide]], and [[hydroxyl radical]], commonly associated with cell damage. ROS form as a natural by-product of the normal metabolism of [[oxygen]] and have important roles in cell signaling.
Two important oxygen-centered radicals are [[superoxide]] and [[hydroxyl radical]]. They derive from molecular oxygen under reducing conditions. However, because of their reactivity, these same radicals can participate in unwanted side reactions resulting in cell damage. Excessive amounts of these radicals can lead to cell injury and [[death]], which may contribute to many diseases such as [[cancer]], [[stroke]], [[myocardial infarction]], [[diabetes]] and major disorders.<ref>{{Cite journal |last=Rajamani Karthikeyan |last2=Manivasagam T |last3=Anantharaman P |last4=Balasubramanian T |last5=Somasundaram ST |year=2011 |title=Chemopreventive effect of Padina boergesenii extracts on ferric nitrilotriacetate (Fe-NTA)-induced oxidative damage in Wistar rats |journal=J. Appl. Phycol. |volume=23 |issue=2 |pages=257–63 |doi=10.1007/s10811-010-9564-0 |s2cid=27537163}}</ref> Many forms of [[cancer]] are thought to be the result of reactions between radicals and [[DNA]], potentially resulting in [[mutation]]s that can adversely affect the [[cell cycle]] and potentially lead to malignancy.<ref>{{Cite journal |last=Mukherjee |first=P.K. |last2=Marcheselli |first2=V.L. |last3=Serhan |first3=C.N. |last4=Bazan |first4=N.G. |year=2004 |title=Neuroprotecin D1: A docosahexanoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress |journal=Proceedings of the National Academy of Sciences of the USA |volume=101 |issue=22 |pages=8491–96 |bibcode=2004PNAS..101.8491M |doi=10.1073/pnas.0402531101 |pmc=420421 |pmid=15152078 |doi-access=free}}</ref> Some of the symptoms of [[Senescence|aging]] such as [[atherosclerosis]] are also attributed to radical induced oxidation of cholesterol to 7-ketocholesterol.<ref>{{Cite journal |last=Lyons |first=MA |last2=Brown |first2=AJ |year=1999 |title=7-Ketocholesterol |journal=Int. J. Biochem. Cell Biol. |volume=31 |issue=3–4 |pages=369–75 |doi=10.1016/s1357-2725(98)00123-x |pmid=10224662}}</ref> In addition radicals contribute to [[alcohol (drug)|alcohol]]-induced [[liver]] damage, perhaps more than alcohol itself. Radicals produced by [[cigarette]] [[smoke]] are implicated in inactivation of [[alpha 1-antitrypsin]] in the [[lung]]. This process promotes the development of [[emphysema]].

[[Oxybenzone]] has been found to form radicals in sunlight, and therefore may be associated with cell damage as well. This only occurred when it was combined with other ingredients commonly found in sunscreens, like [[titanium oxide]] and [[octyl methoxycinnamate]].<ref>{{Cite journal |last=Serpone |first=N |last2=Salinaro |first2=A |last3=Emeline |first3=AV |last4=Horikoshi |first4=S |last5=Hidaka |first5=H |last6=Zhao |first6=JC |year=2002 |title=An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents |journal=Photochemical & Photobiological Sciences |volume=1 |issue=12 |pages=970–81 |doi=10.1039/b206338g |pmid=12661594 |s2cid=27248506}}</ref>

ROS attack the [[polyunsaturated fatty acid]], [[linoleic acid]], to form a series of [[13-hydroxyoctadecadienoic acid]] and [[9-hydroxyoctadecadienoic acid]] products that serve as signaling molecules that may trigger responses that counter the tissue injury which caused their formation. ROS attacks other polyunsaturated fatty acids, e.g. [[arachidonic acid]] and [[docosahexaenoic acid]], to produce a similar series of signaling products.<ref>{{Cite journal |last=Njie-Mbye |first=Ya Fatou |last2=Kulkarni-Chitnis |first2=Madhura |last3=Opere |first3=Catherine A. |last4=Barrett |first4=Aaron |last5=Ohia |first5=Sunny E. |year=2013 |title=Lipid peroxidation: pathophysiological and pharmacological implications in the eye |journal=Frontiers in Physiology |volume=4 |page=366 |doi=10.3389/fphys.2013.00366 |pmc=3863722 |pmid=24379787 |doi-access=free}}</ref>

Reactive oxygen species are also used in controlled reactions involving singlet dioxygen <math>{}^{1}\mathrm{O}_2</math> known as type II [[photooxygenation]] reactions after [[Dexter electron transfer|Dexter]] energy transfer ([[triplet-triplet annihilation]]) from natural triplet dioxygen <math>{}^{3}\mathrm{O}_2</math> and triplet excited state of a photosensitizer. Typical chemical transformations with this singlet dioxygen species involve, among others, conversion of cellulosic biowaste into new [[Polymethine dyes|poylmethine]] dyes.<ref>{{Cite journal |last=Desvals |first=Arthur |last2=Fortino |first2=Mariagrazia |last3=Lefebvre |first3=Corentin |last4=Rogier |first4=Johann |last5=Michelin |first5=Clément |last6=Alioui |first6=Samy |last7=Rousset |first7=Elodie |last8=Pedone |first8=Alfonso |last9=Lemercier |first9=Gilles |last10=Hoffmann |first10=Norbert |date=2022-05-16 |title=Synthesis and characterization of polymethine dyes carrying thiobarbituric and carboxylic acid moieties |url=https://hal.archives-ouvertes.fr/hal-03653553v2/file/NJC%20polymethine%2027042022%20%20red%20hal%202%20V.pdf |journal=New Journal of Chemistry |language=en |volume=46 |issue=19 |pages=8971–8980 |doi=10.1039/D2NJ00684G |issn=1369-9261 |s2cid=248165785}}</ref>

==Depiction in chemical reactions==
<!-- "Mass spectrum analysis" links here --> 
In chemical equations, radicals are frequently denoted by a dot placed immediately to the right of the atomic symbol or molecular formula as follows:

:<math>\mathrm{Cl}_2 \; \xrightarrow{UV} \; 2 {\mathrm{Cl} ^\bullet} </math>

Radical [[reaction mechanism]]s use single-headed arrows to depict the movement of single electrons:

[[File:Internal radical.svg|centre|thumb|upright=1.8|Example of an arrow-pushing mechanism for an internal radical reaction.]]

The [[Homolysis (chemistry)|homolytic]] cleavage of the breaking bond is drawn with a "fish-hook" arrow to distinguish from the usual movement of two electrons depicted by a standard curly arrow. The second electron of the breaking bond also moves to pair up with the attacking radical electron.

Radicals also take part in [[radical addition]] and [[radical substitution]] as [[reactive intermediate]]s. [[Chain reaction#Chemical chain reactions|Chain reactions]] involving radicals can usually be divided into three distinct processes. These are ''initiation'', ''propagation'', and ''termination''.
*''Initiation'' reactions are those that result in a net increase in the number of radicals. They may involve the formation of radicals from stable species as in Reaction 1 above or they may involve reactions of radicals with stable species to form more radicals.
*''Propagation'' reactions are those reactions involving radicals in which the total number of radicals remains the same.
*''Termination'' reactions are those reactions resulting in a net decrease in the number of radicals. Typically two radicals combine to form a more stable species, for example:
*:2 Cl<sup>•</sup> → Cl<sub>2</sub>

==History and nomenclature==
[[File:Gombergm01.jpg|upright|thumb|[[Moses Gomberg]] (1866–1947), the founder of radical chemistry]]
Until late in the 20th century the word "radical" was used in chemistry to indicate any connected group of atoms, such as a [[methyl|methyl group]] or a [[carboxyl]], whether it was part of a larger molecule or a molecule on its own. A radical is often known as an [[R group (disambiguation)|R group]]. The qualifier "free" was then needed to specify the unbound case. Following recent nomenclature revisions, a part of a larger molecule is now called a [[functional group]] or [[substituent]], and "radical" now implies "free". However, the old nomenclature may still appear in some books.

The term radical was already in use when the now obsolete [[radical theory]] was developed. [[Louis-Bernard Guyton de Morveau]] introduced the phrase "radical" in 1785 and the phrase was employed by [[Antoine Lavoisier]] in 1789 in his [[Traité Élémentaire de Chimie]]. A radical was then identified as the root base of certain acids (the Latin word "radix" meaning "root"). Historically, the term ''radical'' in [[radical theory]] was also used for bound parts of the molecule, especially when they remain unchanged in reactions. These are now called [[functional group]]s. For example, [[methanol|methyl alcohol]] was described as consisting of a methyl "radical" and a hydroxyl "radical". Neither are radicals in the modern chemical sense, as they are permanently bound to each other, and have no unpaired, reactive electrons; however, they can be observed as radicals in [[mass spectrometry]] when broken apart by irradiation with energetic electrons.

In a modern context the first [[organic compound|organic]] (carbon–containing) radical identified was the [[triphenylmethyl radical]], (C<sub>6</sub>H<sub>5</sub>)<sub>3</sub>C<sup>•</sup>. This species was discovered by [[Moses Gomberg]] in 1900. In 1933 [[Morris S. Kharasch]] and [[Frank R. Mayo|Frank Mayo]] proposed that free radicals were responsible for [[anti-Markovnikov addition]] of [[hydrogen bromide]] to [[allyl bromide]].<ref>{{Cite journal |last=Kharasch |first=M. S. |year=1933 |title=The Peroxide Effect in the Addition of Reagents to Unsaturated Compounds. I. The Addition of Hydrogen Bromide to Allyl Bromide |journal=Journal of the American Chemical Society |volume=55 |issue=6 |pages=2468–2496 |doi=10.1021/ja01333a041}}</ref><ref>{{Cite journal |last=Yan |first=M |last2=Lo |first2=JC |last3=Edwards |first3=JT |last4=Baran |first4=PS |year=2016 |title=Radicals: Reactive Intermediates with Translational Potential |journal=J Am Chem Soc |volume=138 |issue=39 |pages=12692–12714 |doi=10.1021/jacs.6b08856 |pmc=5054485 |pmid=27631602}}</ref>

In most fields of chemistry, the historical definition of radicals contends that the molecules have nonzero electron spin. However, in fields including [[spectroscopy]] and [[astrochemistry]], the definition is slightly different. [[Gerhard Herzberg]], who won the Nobel prize for his research into the electron structure and geometry of radicals, suggested a looser definition of free radicals: "any transient (chemically unstable) species (atom, molecule, or ion)".<ref>G. Herzberg (1971), "The spectra and structures of simple free radicals", {{ISBN|0-486-65821-X}}.</ref> The main point of his suggestion is that there are many chemically unstable molecules that have zero spin, such as C<sub>2</sub>, C<sub>3</sub>, CH<sub>2</sub> and so on. This definition is more convenient for discussions of transient chemical processes and astrochemistry; therefore researchers in these fields prefer to use this loose definition.<ref>[http://www.free-radicals-symposium-05.ch/index2.html 28th International Symposium on Free Radicals] {{webarchive|url=https://web.archive.org/web/20070716014949/http://www.free-radicals-symposium-05.ch/index2.html |date=2007-07-16}}.</ref>

==See also==
* [[Electron pair]]
* [[Globally Harmonized System of Classification and Labelling of Chemicals]]
* [[Hofmann–Löffler reaction]]
;Free radical research
* [[Free Radical Centre|ARC Centre of Excellence for Free Radical Chemistry and Biotechnology]]

==References==
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[[Category:Free radicals| ]]
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[[Category:Biological processes]]
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[[Category:Environmental chemistry]]
[[Category:Senescence]]