View source for Biology:Radical

{{short description|Atom, molecule, or ion that has an unpaired valence electron; typically highly reactive}}
[[File:Hydroxyl radical.svg|thumb|upright=0.5|The hydroxyl radical, Lewis structure shown, contains one unpaired electron.]]
[[File:Hydroxide vs hydroxyl.svg|thumb|[[Chemistry:Hydroxide|Hydroxide]] ion compared to a hydroxyl radical]]
In [[Chemistry:Chemistry|chemistry]], a '''radical''', also known as a '''free radical''', is an [[Physics:Atom|atom]], [[Physics:Molecule|molecule]], or [[Physics:Ion|ion]] that has at least one [[Chemistry: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 | last1 = Hayyan | first1 = 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 [[Chemistry:Chemical reaction|chemically reactive]].  Many radicals spontaneously [[Chemistry:Dimer|dimerize]].  Most organic radicals have short lifetimes.

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

Radicals may be generated in a number of ways, but typical methods involve redox reactions, [[Physics:Ionizing radiation|Ionizing radiation]], heat, electrical discharges, and [[Chemistry:Electrolysis|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 [[Physics:Combustion|combustion]], [[Earth:Atmospheric chemistry|atmospheric chemistry]], [[Chemistry:Polymerization|polymerization]], [[Physics:Plasma|plasma]] chemistry, [[Biology:Biochemistry|biochemistry]], and many other chemical processes. A majority of natural products are generated by radical-generating enzymes.  In living organisms, the radicals [[Chemistry:Superoxide|superoxide]] and [[Chemistry:Nitric oxide|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 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 [[Chemistry:Homolysis|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]]
[[Chemistry:Homolysis|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"/> Because breaking a chemical bond requires energy, homolysis occurs under the addition of heat or light. The [[Physics:Bond-dissociation energy|bond dissociation energy]] associated with homolysis depends on the stability of a given compound, and some weak bonds are able to homolyze at relatively lower temperatures.

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====
[[File: Lithium Naphthalenide.jpg|thumb|left|The deep colour of [[Chemistry:Lithium naphthalene|lithium naphthalene]] results from the lithium naphthanide radical.|120px]]
Classically radicals form by one-electron [[Chemistry:Redox|reduction]]s.  Typically one-electron reduced organic compounds are unstable. Stability is conferred to the radical anion when the charge can be delocalized.  Examples include alkali metal [[Chemistry:Lithium naphthalene|naphthenide]]s, [[Chemistry:Anthracene|anthracenide]]s, and [[Chemistry:Ketyl|ketyl]]s.

===Radical formation from other radicals===

====Abstraction====
[[File:Abstraction.svg|thumb|upright=1.95|Radical abstraction between a benzoyloxy radical and hydrogen bromide]]
[[Chemistry:Hydrogen atom abstraction|Hydrogen abstraction]] generates radicals.  To achieve this reaction, the C-H bond of the H-atom donor must 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 [[Chemistry:Drying oil|drying oil]]s, such as [[Chemistry:Linoleic acid|linoleic acid]] derivatives.

====Addition====
[[File:radicaladdition.svg|thumb|upright=1.15|Radical addition of a bromine radical to a substituted alkene]]
In [[Chemistry:Free-radical addition|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 [[Chemistry:Radical polymerization|radical polymerization]], technology that produces many [[Chemistry:Plastic|plastic]]s.<ref>{{cite journal |doi=10.1021/cr9901236 |title=Catalytic Chain Transfer in Free-Radical Polymerizations |date=2001 |last1=Gridnev |first1=Alexei A. |last2=Ittel |first2=Steven D. |journal=Chemical Reviews |volume=101 |issue=12 |pages=3611–3660 |pmid=11740917 }}</ref><ref>{{cite journal |doi=10.1021/cr00017a019 |title=Photoinitiators for free-radical-initiated photoimaging systems |date=1993 |last1=Monroe |first1=Bruce M. |last2=Weed |first2=Gregory C. |journal=Chemical Reviews |volume=93 |pages=435–448 }}</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|pages=137–183|editor-last=Su|editor-first=Wei-Fang|series=Lecture Notes in Chemistry|volume=82|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==
<!--Single-electron transfer and Single electron transfer redirect here-->

===Stability of organic radicals===
[[File:Vitamin E radical.svg |thumb|upright=1.5|The radical derived from ''α-tocopherol'']]
Although organic radicals are generally stable intrinsically (in isolation), practically speaking their existence is only transient because they tend to dimerize. Some are quite long-lived. Generally organic radicals are stabilized by any or all of these factors: presence of electronegativity, delocalization, and steric hindrance.<ref>{{cite journal|doi=10.1021/ar50097a003|title=Persistent carbon-centered radicals|year=1976|last1=Griller|first1=David|first2=Keith U.|journal=Accounts of Chemical Research|volume=9|pages=13–19|last2=Ingold}}</ref>  The compound [[Chemistry:TEMPO|2,2,6,6-tetramethylpiperidinyloxyl]] illustrates the combination of all three factors.  It is a commercially available solid that, aside from being magnetic, behaves like a normal organic compound.

==== Electronegativity ====
Organic radicals are inherently electron deficient thus the greater the electronegativity of the atom on which the unpaired electron resides the less stable the radical.<ref name=":0">{{Cite book|last=Forrester|first=A.R.|title=Organic Chemistry of Stable Free Radicals|publisher=London: Academic Press|year=1968|pages=1–6}}</ref> Between carbon, nitrogen, and oxygen, for example, carbon is the most stable and oxygen the least stable.

Electronegativity also factors into the stability of carbon atoms of different hybridizations. Greater s-character correlates to higher electronegativity of the carbon atom (due to the close proximity of s orbitals to the nucleus), and the greater the electronegativity the less stable a radical.<ref name=":0" /> sp-hybridized carbons (50% s-character) form the least stable radicals compared to sp3-hybridized carbons (25% s-character) which form the most stable radicals.

==== Delocalization ====
The delocalization of electrons across the structure of a radical, also known as its ability to form one or more resonance structures, allows for the electron-deficiency to be spread over several atoms, minimizing instability. Delocalization usually occurs in the presence of electron-donating groups, such as hydroxyl groups (−OH), ethers (−OR), adjacent alkenes, and amines (−NH<sub>2</sub> or −NR), or electron-withdrawing groups, such as C=O or C≡N.<ref name=":1">{{Cite book|last1=Clayden, Jonathan|url=https://www.worldcat.org/oclc/761379371|title=Organic chemistry|date=2012|publisher=Oxford University Press|last2=Greeves |first2=Nick |last3=Warren |first3=Stuart G.|isbn=978-0-19-927029-3|edition=2nd |location=Oxford|oclc=761379371}}</ref>

[[File:Electron-Donating Diagram.svg|thumb|upright=1.3|Molecular orbital diagram of a radical with an electron-donating group]]
Delocalization effects can also be understood using [[Chemistry:Molecular orbital theory|molecular orbital theory]] as a lens, more specifically, by examining the intramolecular interaction of the unpaired electron with a donating group's pair of electrons or the empty π* orbital of an electron-withdrawing group in the form of a molecular orbital diagram. The HOMO of a radical is singly-occupied hence the orbital is aptly referred to as the SOMO, or the Singly-Occupied Molecular Orbital. For an electron-donating group, the SOMO interacts with the lower energy lone pair to form a new lower-energy filled bonding-orbital and a singly-filled new SOMO, higher in energy than the original. While the energy of the unpaired electron has increased, the decrease in energy of the lone pair forming the new bonding orbital outweighs the increase in energy of the new SOMO, resulting in a net decrease of the energy of the molecule. Therefore, electron-donating groups help stabilize radicals.
[[File:Electron-Withdrawing Diagram.svg|thumb|upright=1.3|Molecular orbital diagram of a radical with an electron-withdrawing group]]
With a group that is instead electron-withdrawing, the SOMO then interacts with the empty π* orbital. There are no electrons occupying the higher energy orbital formed, while a new SOMO forms that is lower in energy. This results in a lower energy and higher stability of the radical species. Both donating groups and withdrawing groups stabilize radicals.

Another well-known albeit weaker form of delocalization is [[Chemistry:Hyperconjugation|hyperconjugation]]. In radical chemistry, radicals are stabilized by hyperconjugation with adjacent alkyl groups. The donation of sigma (σ) C−H bonds into the partially empty radical orbitals helps to differentiate the stabilities of radicals on tertiary, secondary, and primary carbons. Tertiary carbon radicals have three σ C-H bonds that donate, secondary radicals only two, and primary radicals only one. Therefore, tertiary radicals are the most stable and primary radicals the least stable.
[[File:radical hyperconjugation.svg|thumb|center|upright=1.6|The relative stabilities of tertiary, secondary, primary and methyl radicals can be explained by hyperconjugation]]

==== Steric hindrance ====
[[File:N-hydroxypiperidine Radical Form.svg|thumb|upright=0.4|Radical form of ''N''-hydroxypiperidine]]
Most simply, the greater the steric hindrance the more difficult it is for reactions to take place, and the radical form is favored by default. For example, compare the hydrogen-abstracted form of [[Chemistry:N-Hydroxypiperidine|''N''-hydroxypiperidine]] to the molecule [[Chemistry:TEMPO|TEMPO]].<ref name=":1" /> TEMPO, or (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl, is too sterically hindered by the additional methyl groups to react making it stable enough to be sold commercially in its radical form. ''N''-Hydroxypiperidine, however, does not have the four methyl groups to impede the way of a reacting molecule so the structure is unstable.<ref name=":1" />

====Facile H-atom donors====
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 [[Chemistry:Tocopherol|α-tocopherol]] ([[Chemistry:Vitamin E|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.  
thumb|upright=1.1|[[TEMPO|2,2,6,6-Tetramethylpiperidinyloxyl is an example of a robust organic radical.]]

==Inorganic radicals==
A large variety of inorganic radicals are stable and in fact isolable.  Examples include most first-row transition metal complexes.

With regard to main group radicals, the most abundant radical in the universe is also the most abundant chemical in the universe, H<sup>•</sup>.  Most main group radicals are not however ''isolable'', despite their intrinsic stability.  Hydrogen radicals for example combine eagerly to form H<sub>2</sub>.  [[Chemistry:Nitric oxide|Nitric oxide]] (NO) is well known example of an isolable inorganic radical.  Fremy's salt (Potassium nitrosodisulfonate, (KSO<sub>3</sub>)<sub>2</sub>NO) is a related example. Many [[Chemistry:Tetrasulfur tetranitride|thiazyl]] radicals are known, despite limited extent of π resonance stabilization.<ref>{{cite book | last1 = Oakley | first1 = Richard T. | title = Progress in Inorganic Chemistry | volume = 36 | pages = 299–391 | year = 1988 | doi = 10.1002/9780470166376.ch4 | chapter-url = http://www.chembio.uoguelph.ca/oakley/papers/rto_086.pdf | department = Cyclic and Heterocyclic Thiazenes (section) | series = Progress in Inorganic Chemistry | isbn = 978-0-470-16637-6 | chapter = Cyclic and Heterocyclic Thiazenes | access-date = 2011-03-31 | archive-date = 2015-09-23 | archive-url = https://web.archive.org/web/20150923202507/http://www.chembio.uoguelph.ca/oakley/papers/rto_086.pdf | url-status = dead }}</ref><ref>{{cite book | last1 = Rawson | first1 = J | last2 = Banister | first2 = A | last3 = Lavender | first3 = I | volume = 62 | pages = 137–247 | year = 1995 | doi = 10.1016/S0065-2725(08)60422-5 | title = The Chemistry of Dithiadiazolylium and Dithiadiazolyl Rings  | series = Advances in Heterocyclic Chemistry | isbn = 978-0-12-020762-6  }}</ref>

Many radicals can be envisioned as the products of [[Chemistry:Bond cleavage|breaking of covalent bonds]] by [[Chemistry:Homolysis|homolysis]]. The homolytic 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.

==Diradicals==
[[Chemistry:Diradical|Diradical]]s are molecules containing two radical centers. [[Chemistry:Dioxygen|Dioxygen]] (O<sub>2</sub>) is an important example of a stable diradical. [[Chemistry:Singlet oxygen|Singlet oxygen]], the lowest-energy non-radical state of dioxygen, is less stable than the diradical due to [[Chemistry:Hund's rule of maximum multiplicity|Hund's rule of maximum multiplicity]]. The relative stability of the oxygen diradical is primarily due to the [[Chemistry: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, [[Physics:Paramagnetism|paramagnetism]] does not necessarily imply radical character.</ref> Diradicals can also occur in [[Chemistry:Transition metal oxo complex|metal-oxo complexes]], lending themselves for studies of spin forbidden reactions in [[Chemistry:Transition metal|transition metal]] chemistry.<ref>{{Cite journal|last1=Linde|first1=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> [[Chemistry:Carbene|Carbene]]s in their triplet state can be viewed as diradicals centred on the same atom, while these are usually highly reactive [[Chemistry:Persistent carbene|persistent carbene]]s are known, with N-heterocyclic carbenes being the most common example.

Triplet [[Chemistry:Carbene|carbene]]s and [[Chemistry:Nitrene|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 [[Chemistry:Butane|butane]] torch showing excited molecular radical band emission and Swan bands]]
A familiar radical reaction is [[Physics:Combustion|combustion]]. The [[Chemistry:Oxygen|oxygen]] molecule is a stable [[Chemistry:Diradical|diradical]], best represented by <sup>•</sup>O–O<sup>•</sup>. Because [[Physics:Spin|spins]] of the electrons are parallel, this molecule is stable.  While the [[Physics:Ground state|ground state]] of oxygen is this unreactive spin-unpaired ([[Chemistry:Triplet oxygen|triplet]]) diradical, an extremely reactive spin-paired ([[Chemistry: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 "[[Physics: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 [[Physics:Combustion|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 ([[Engineering:Engine knocking|engine knocking]]) or premature ignition (preignition).

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

===Polymerization===
Many [[Chemistry:Polymerization|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, [[Chemistry:Methyl methacrylate|methyl methacrylate]] (MMA) can be polymerized to produce [[Chemistry:Poly(methyl methacrylate)|Poly(methyl methacrylate)]] (PMMA - Plexiglas or Perspex) via a repeating series of [[Chemistry:Free-radical addition|radical addition]] steps:  
upright=3.35|center|thumb|Radical intermediates in the formation of polymethacrylate (plexiglas or perspex)

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

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

===Atmospheric radicals===
The most common radical in the lower atmosphere is molecular dioxygen. [[Astronomy:Photodissociation|Photodissociation]] of source molecules produces other radicals. In the lower atmosphere, important radical are produced by the photodissociation of [[Chemistry:Nitrogen dioxide|nitrogen dioxide]] to an oxygen atom and [[Chemistry:Nitric oxide|nitric oxide]] (see {{EquationNote|eq. 1.1}} below), which plays a key role in 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 [[Earth:Chlorofluorocarbon|chlorofluorocarbon]]s (CFCs) by solar ultraviolet radiation is an important source of radicals (see eq. 1 below). These reactions give the [[Chemistry:Chlorine|chlorine]] radical, Cl<sup>•</sup>, which catalyzes the conversion of [[Chemistry:Ozone|ozone]] to O<sub>2</sub>, thus facilitating [[Earth:Ozone depletion|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 [[Physics:Ozone layer|ozone layer]], especially since the chlorine radical is free to engage in another reaction chain; consequently, the use of chlorofluorocarbons as [[Chemistry:Refrigerant|refrigerant]]s has been restricted.

===In biology===
[[File:DeoxyadenosylRadical.png|thumb|Structure of the [[Chemistry:Deoxyadenosyl radical|deoxyadenosyl radical]], a common biosynthetic intermediate<ref>{{cite journal|author1=Broderick, J.B. |author2=Duffus, B.R. |author3=Duschene, K.S. |author4=Shepard, E.M. |title=Radical S-Adenosylmethionine Enzymes|journal=Chemical Reviews|year=2014|volume=114|issue=8|pages=4229–317|doi= 10.1021/cr4004709|pmid=24476342|pmc=4002137}}</ref>]]
[[Image:Lignin structure.svg|thumb|upright=2.25|An approximate structure of [[Biology:Lignin|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 granulocytes and [[Biology:Macrophage|macrophage]]s. Radicals are involved in [[Biology:Signal transduction|cell signalling]] processes,<ref>{{cite journal |vauthors=Pacher P, Beckman JS, Liaudet L |title=Nitric oxide and peroxynitrite in health and disease |journal=Physiol. Rev. |volume=87 |issue=1 |pages=315–424 |year=2007 |pmid=17237348 |doi=10.1152/physrev.00029.2006 |pmc=2248324}}</ref> known as redox signaling.  For example, radical attack of [[Chemistry:Linoleic acid|linoleic acid]] produces a series of 13-hydroxyoctadecadienoic acids and 9-hydroxyoctadecadienoic acids, 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|doi=10.3389/fphys.2013.00366 | pmid=24379787 | pmc=3863722 | volume=4 | pages=366 | title=Lipid peroxidation: pathophysiological and pharmacological implications in the eye | journal=Frontiers in Physiology| year=2013 | last1=Njie-Mbye | first1=Ya Fatou | last2=Kulkarni-Chitnis | first2=Madhura | last3=Opere | first3=Catherine A. | last4=Barrett | first4=Aaron | last5=Ohia | first5=Sunny E. | doi-access=free }}</ref>

Radicals may also be involved in [[Medicine:Parkinson's disease|Parkinson's disease]], senile and drug-induced [[Medicine:Deafness|deafness]], [[Medicine:Schizophrenia|schizophrenia]], and Alzheimer's.<ref>{{cite journal | last1 = Floyd | first1 = 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 [[Chemistry:Melanin|melanin]] abnormalities, deafness, arthritis, and diabetes mellitus. The free-radical theory of aging proposes that radicals underlie the [[Biology:Senescence|aging process]] itself. Similarly, the process of mito[[Biology:Hormesis|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 [[Biology:Enzyme|enzyme]]s [[Biology:Superoxide dismutase|superoxide dismutase]], [[Biology:Catalase|catalase]], [[Biology:Glutathione peroxidase|glutathione peroxidase]] and [[Biology:Glutathione reductase|glutathione reductase]]. In addition, [[Biology:Antioxidant|antioxidant]]s play a key role in these defense mechanisms. These are often the three vitamins, [[Chemistry:Vitamin A|vitamin A]], [[Biology:Vitamin C|vitamin C]] and [[Chemistry:Vitamin E|vitamin E]] and polyphenol antioxidants. Furthermore, there is good evidence indicating that [[Chemistry:Bilirubin|bilirubin]] and [[Chemistry:Uric acid|uric acid]] can act as antioxidants to help neutralize certain radicals. Bilirubin comes from the breakdown of [[Biology:Red blood cell|red blood cell]]s' contents, while uric acid is a breakdown product of [[Chemistry:Purine|purine]]s. Too much bilirubin, though, can lead to [[Medicine:Jaundice|jaundice]], which could eventually damage the central nervous system, while too much uric acid causes [[Medicine:Gout|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|author=Rhodes C.J.|title=Toxicology of the Human Environment – the critical role of free radicals|publisher=Taylor and Francis|place= London|year= 2000|isbn= 978-0-7484-0916-7}}</ref>

===Reactive oxygen species===
[[Biology:Reactive oxygen species|Reactive oxygen species]] or ROS are species such as [[Chemistry:Superoxide|superoxide]], [[Chemistry:Hydrogen peroxide|hydrogen peroxide]], and [[Chemistry:Hydroxyl radical|hydroxyl radical]], commonly associated with cell damage. ROS form as a natural by-product of the normal metabolism of [[Chemistry:Oxygen|oxygen]] and have important roles in cell signaling.
Two important oxygen-centered radicals are [[Chemistry:Superoxide|superoxide]] and [[Chemistry:Hydroxyl radical|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 [[Biology:Death|death]], which may contribute to many diseases such as [[Medicine:Cancer|cancer]], [[Medicine:Stroke|stroke]], [[Medicine:Myocardial infarction|myocardial infarction]], [[Medicine:Diabetes|diabetes]] and major disorders.<ref>{{cite journal |author1=Rajamani Karthikeyan |author2=Manivasagam T |author3=Anantharaman P |author4=Balasubramanian T |author5=Somasundaram ST |title=Chemopreventive effect of Padina boergesenii extracts on ferric nitrilotriacetate (Fe-NTA)-induced oxidative damage in Wistar rats |journal=J. Appl. Phycol.| year=2011|doi=10.1007/s10811-010-9564-0 |volume=23 |issue=2 |pages=257–63|s2cid=27537163 }}
</ref> Many forms of [[Medicine:Cancer|cancer]] are thought to be the result of reactions between radicals and [[Biology:DNA|DNA]], potentially resulting in [[Biology:Mutation|mutation]]s that can adversely affect the [[Biology:Cell cycle|cell cycle]] and potentially lead to malignancy.<ref>{{cite journal | last1 = Mukherjee | first1 = 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 | doi = 10.1073/pnas.0402531101 | pmid=15152078 | pmc=420421| bibcode = 2004PNAS..101.8491M | doi-access = free }}</ref> Some of the symptoms of [[Biology:Senescence|aging]] such as [[Medicine:Atherosclerosis|atherosclerosis]] are also attributed to radical induced oxidation of cholesterol to 7-ketocholesterol.<ref>{{cite journal |pmid=10224662 | volume=31 | issue=3–4 | title=7-Ketocholesterol | year=1999 | journal=Int. J. Biochem. Cell Biol. | pages=369–75 | last1 = Lyons | first1 = MA | last2 = Brown | first2 = AJ | doi = 10.1016/s1357-2725(98)00123-x }}</ref> In addition radicals contribute to [[Chemistry:Alcohol (drug)|alcohol]]-induced [[Biology:Liver|liver]] damage, perhaps more than alcohol itself. Radicals produced by [[Engineering:Cigarette|cigarette]] [[Earth:Smoke|smoke]] are implicated in inactivation of alpha 1-antitrypsin in the [[Medicine:Lung|lung]]. This process promotes the development of emphysema.

[[Chemistry:Oxybenzone|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 [[Chemistry:Titanium oxide|titanium oxide]] and [[Chemistry:Octyl methoxycinnamate|octyl methoxycinnamate]].<ref>{{cite journal | last1 = Serpone | first1 = 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 [[Chemistry:Polyunsaturated fatty acid|polyunsaturated fatty acid]], [[Chemistry:Linoleic 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. [[Chemistry:Arachidonic acid|arachidonic acid]] and [[Chemistry:Docosahexaenoic acid|docosahexaenoic acid]], to produce a similar series of signaling products.<ref>{{cite journal | doi = 10.3389/fphys.2013.00366 | volume=4 | title=Lipid peroxidation: pathophysiological and pharmacological implications in the eye | journal=Frontiers in Physiology| year=2013 | last1=Njie-Mbye | first1=Ya Fatou | last2=Kulkarni-Chitnis | first2=Madhura | last3=Opere | first3=Catherine A. | last4=Barrett | first4=Aaron | last5=Ohia | first5=Sunny E. | page=366 | 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 [[Physics:Photooxygenation|photooxygenation]] reactions after [[Physics:Dexter electron transfer|Dexter]] energy transfer ([[Physics:Triplet-triplet annihilation|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 poylmethine dyes.<ref>{{Cite journal |last1=Desvals |first1=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 |s2cid=248165785 |issn=1369-9261}}</ref>

==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 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. 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 [[Chemistry:Functional group|functional group]] or [[Chemistry:Substituent|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 [[Chemistry:Radical theory|radical theory]] was developed. Louis-Bernard Guyton de Morveau introduced the phrase "radical" in 1785 and the phrase was employed by [[Biography:Antoine Lavoisier|Antoine Lavoisier]] in 1789 in his [[Chemistry:Traité Élémentaire de Chimie|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 [[Chemistry:Radical theory|radical theory]] was also used for bound parts of the molecule, especially when they remain unchanged in reactions. These are now called [[Chemistry:Functional group|functional group]]s. For example, [[Chemistry: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 [[Physics:Mass spectrometry|mass spectrometry]] when broken apart by irradiation with energetic electrons.

In a modern context the first [[Chemistry:Organic compound|organic]] (carbon–containing) radical identified was the [[Chemistry:Triphenylmethyl radical|triphenylmethyl radical]], (C<sub>6</sub>H<sub>5</sub>)<sub>3</sub>C<sup>•</sup>.  This species was discovered by [[Biography:Moses Gomberg|Moses Gomberg]] in 1900. In 1933 Morris S. Kharasch and Frank Mayo proposed that free radicals were responsible for anti-Markovnikov addition of [[Chemistry:Hydrogen bromide|hydrogen bromide]] to [[Chemistry:Allyl bromide|allyl bromide]].<ref>{{cite journal | doi = 10.1021/ja01333a041 | volume=55 | title=The Peroxide Effect in the Addition of Reagents to Unsaturated Compounds. I. The Addition of Hydrogen Bromide to Allyl Bromide | year=1933 | journal=Journal of the American Chemical Society | pages=2468–2496 | last1 = Kharasch | first1 = M. S.| issue=6 }}</ref><ref>{{cite journal | doi = 10.1021/jacs.6b08856 | pmid = 27631602 | volume=138 | title=Radicals: Reactive Intermediates with Translational Potential | pmc=5054485 | year=2016 | journal=J Am Chem Soc | pages=12692–12714 | last1 = Yan | first1 = M | last2 = Lo | first2 = JC | last3 = Edwards | first3 = JT | last4 = Baran | first4 = PS| issue = 39 }}</ref>

In most fields of chemistry, the historical definition of radicals contends that the molecules have nonzero electron spin. However, in fields including [[Physics:Spectroscopy|spectroscopy]] and [[Chemistry:Astrochemistry|astrochemistry]], the definition is slightly different. [[Biography:Gerhard Herzberg|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>

==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 [[Physics:Reaction mechanism|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 [[Chemistry:Homolysis|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 [[Chemistry:Radical substitution|radical substitution]] as [[Chemistry:Reactive intermediate|reactive intermediate]]s. [[Philosophy: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>

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

==References==
{{reflist|30em}}


[[Category:Free radicals| ]]
[[Category:Biological processes]]
[[Category:Biomolecules]]
[[Category:Chemical bonding]]
[[Category:Environmental chemistry]]
[[Category:Senescence]]

{{Sourceattribution|Radical (chemistry)|1}}