Free radicals
Radicals (often referred to as free radicals) are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative or zero charge. Even though they have unpaired electrons, by convention, metals and their ions or complexes with unpaired electrons are not radicals. With some exceptions, the unpaired electrons cause radicals to be highly chemically reactive.
On the other word, Free radical, radical (an atom or group of atoms with at least one unpaired electron; in the body it is usually an oxygen molecule that has lost an electron and will stabilize itself by stealing an electron from a nearby molecule) "in the body free radicals are high-energy particles that ricochet wildly and damage cells"
Free radicals play an important role in combustion, atmospheric chemistry, polymerization, plasma chemistry, biochemistry, and many other chemical processes, including human physiology. For example, superoxide and nitric oxide regulate many biological processes, such as controlling vascular tone. Such radicals can even be messengers in a phenomenon dubbed redox signaling. "Radical" and "free radical" are frequently used interchangeably, although a radical may be trapped within a solvent cage or be otherwise bound.
Formation
The formation of radicals may involve breaking of covalent bonds homolytically, a process that requires significant amounts of energy. For example, splitting H2 into 2H· has a ΔH° of +435 kJ/mol, and Cl2 into 2Cl· has a ΔH° of +243 kJ/mol. This is known as the homolytic bond dissociation energy, and is usually abbreviated as the symbol DH°. The bond energy between two covalently bonded atoms is affected by the structure of the molecule as a whole, not just the identity of the two atoms, and radicals requiring more energy to form are less stable than those requiring less energy. Homolytic bond cleavage most often happens between two atoms of similar electronegativity. In organic chemistry this is often the O-O bond in peroxide species or O-N bonds. Sometimes radical formation is spin-forbidden, presenting an additional barrier. However, propagation is a very exothermic reaction. Note that most species are electrically neutral although radical ions do exist.
Radicals may also be formed by single electron oxidation or reduction of an atom or molecule. An example is the production of superoxide by the electron transport chain.
Depicting radicals in chemical reactions
In chemical equations, free radicals are frequently denoted by a dot placed immediately to the right of the atomic symbol or molecular formula as follows:
Chlorine gas can be broken down by ultraviolet light to form atomic chlorine radicals.
Radical reaction mechanisms use single-headed arrows to depict the movement of single electrons:
The 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. It should be noted that the second electron of the breaking bond also moves to pair up with the attacking radical electron; this is not explicitly indicated in this case.
Free radicals take part in radical addition and radical substitution as reactive intermediates. Chain reactions involving free radicals can usually be divided into three distinct processes: initiation, propagation, and termination.
- Initiation reactions are those that result in a net increase in the number of free radicals. They may involve the formation of free radicals from stable species as in Reaction 1 above or they may involve reactions of free radicals with stable species to form more free radicals.
- Propagation reactions are those reactions involving free radicals in which the total number of free radicals remains the same.
- Termination reactions are those reactions resulting in a net decrease in the number of free radicals. Typically two free radicals combine to form a more stable species, for example: 2Cl·→ Cl2
Reactivity
Radical alkyl intermediates are stabilized by similar criteria as carbocations: the more substituted the radical center is, the more stable it is. This will direct their reactions: formation of a tertiary radical (R3C·) is favored over secondary (R2HC·), which is favored over primary (RH2C·). Radicals next to functional groups such as carbonyl, nitrile, and ether are more stable than tertiary alkyl radicals. Radicals attack double bonds, but unlike similar ions, they are not as much directed by electrostatic interactions. For example, the reactivity of nucleophilic ions with α,β-unsaturated compounds (C=C–C=O) is directed by the electron-withdrawing effect of the oxygen, resulting in a partial positive charge on the carbonyl carbon. There are two reactions that are observed in the ionic case: the carbonyl is attacked in a direct addition to carbonyl, or the vinyl is attacked in conjugate addition, and in either case, the charge on the nucleophile is taken by the oxygen. Radicals add rapidly to the double bond, and the resulting α-radical carbonyl is relatively stable; it can couple with another molecule or be oxidized. Nonetheless, the electrophilic/neutrophilic character of radicals has been shown in a variety of instances (e.g., in the alternating tendency of the copolymerization of maleic anhydride (electrophilic) and styrene (slightly nucleophilic).
In intramolecular reactions, precise control can be achieved despite the extreme reactivity of radicals. Radicals will attack the closest reactive site the most readily. Therefore, when there is a choice, a preference for five-membered rings is observed: four-membered rings are too strained, and collisions with carbons five or more atoms away in the chain are infrequent.
Atmospheric radicals
The most common radical in the lower atmosphere is molecular dioxygen. Other free radicals are produced through photodissociation of source molecules. In the lower atmosphere, the most important examples of free radical production are the photodissociation of nitrogen dioxide to give an oxygen atom and nitric oxide, which plays a key role in smog formation—and the photodissociation of ozone to give the excited oxygen atom O(1D). In the upper atmosphere, a particularly important source of radicals is the photodissociation of normally unreactive chlorofluorocarbons by solar ultraviolet radiation, or by reactions with other stratospheric constituents. These free radicals, among them the hydroxyl radical OH· predominates, then react with ozone in a catalytic chain reaction, in which destroys the ozone but regenerates the free radical, allowing it to participate in additional reactions. Such reactions are believed to be the primary cause of depletion of the ozone layer and this is why the use of chlorofluorocarbons as refrigerants has been restricted.
Free radicals in biology
Free radicals play an important role in a number of biological processes, some of which are necessary for life, such as the intracellular killing of bacteria by phagocytic cells such as granulocytes and macrophages. Free radicals have also been implicated in certain cell signalling processes. This is dubbed redox signaling.
The two most important oxygen-centered free radicals are superoxide and hydroxyl radical. They are derived from molecular oxygen under reducing conditions. However, because of their reactivity, these same free radicals can participate in unwanted side reactions resulting in cell damage. Excessive amounts of these free radicals can lead to cell injury and death, which results in many diseases such as cancer, stroke, myocardial infarction, diabetes and major disorders. Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy. Some of the symptoms of aging such as atherosclerosis are also attributed to free-radical induced oxidation of many of the chemicals making up the body. In addition free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself. Radicals in cigarette smoke have been implicated in inactivation of alpha 1-antitrypsin in the lung. This process promotes the development of emphysema.
Free radicals may also be involved in Parkinson's disease, senile and drug-induced deafness, schizophrenia, and Alzheimer's. 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 free radicals underlie the aging process itself, whereas the process of mitohormesis suggests that repeated exposure to free radicals may extend life span.
Because free radicals are necessary for life, the body has a number of mechanisms to minimize free radical induced damage and to repair damage that occurs, such as the enzymes superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. In addition, antioxidants play a key role in these defense mechanisms. These are often the three vitamins, vitamin A, vitamin C and vitamin E and polyphenol antioxidants. Further, there is good evidence bilirubin and uric acid can act as antioxidants to help neutralize certain free radicals. Bilirubin comes from the breakdown of red blood cells' contents, while uric acid is a breakdown product of purines. Too much bilirubin, though, can lead to jaundice, which could eventually damage the central nervous system, while too much uric acid causes gout.
Reactive oxygen species
Reactive oxygen species or ROSs are species such as superoxide, hydrogen peroxide, and hydroxyl radical and are associated with cell damage. ROSs forms as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling.
Diagnostics
Free radical diagnostic techniques include:
A widely-used technique for studying free radicals, and other paramagnetic species, is electron spin resonance spectroscopy (ESR). This is alternately referred to as "electron paramagnetic resonance" (EPR) spectroscopy. It is conceptually related to nuclear magnetic resonance, though electrons resonate with higher-frequency fields at a given fixed magnetic field than do most nuclei.
- Nuclear magnetic resonance using a phenomenon called CIDNP
- Chemical labeling
Chemical labelling by quenching with free radicals, e.g. with nitric oxide (NO) or DPPH (2,2-diphenyl-1-picrylhydrazyl), followed by spectroscopic methods like X-ray photoelectron spectroscopy (XPS) or absorption spectroscopy, respectively.
- Use of free radical markers
Stable, specific or non-specific derivates of physiological substances can be measured e.g. lipid peroxidation products (isoprostanes, TBARS), amino acid oxidation products (meta-tyrosine, ortho-tyrosine, hydroxy-Leu, dityrosine etc.), peptide oxidation products (oxidized glutathione - GSSG)
- Indirect method
Measurement of the decrease in the amount of antioxidants (e.g. TAS, reduced glutathione - GSH)
Using a chemical species that reacts with free radicals to form a stable product that can then be readily measured (Hydroxyl radical and salicylic acid)
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