FREE RADICALS

INTRODUCTIONGenerally, molecules bear bonding electron pairs and lone pairs (a non-bonding electron pair or unshared electron pair). Each bonding or non-bonding electron pair has two electrons, which are in opposite spin orientation, + 1/2 and - 1/2, in one orbital based on Paulis exclusion principle, whereas an unpaired electron is a single electron, alone in one orbital. A molecule that has an unpaired electron is called a free radical and is a paramagnetic species. Ethane is composed of two methyl groups connected by a covalent bond and is a very stable compound. The methyl anion and methyl cation have an ionic bond mainly between carbons and counter ions, respectively, and are not particularly unstable, though there are some rather moisture-sensitive species. However, the methyl radical is an extremely unstable and reactive species, because its octet rule on the carbon is not filled. The carbon atom in the methyl cation adopts sp2 hybridization and the structure is triangular (1200) and planar. The carbon atom in the methyl anion adopts sp3 hybridization and the structure is tetrahedral (109.50). However, the carbon atom in the methyl radical adopts a middle structure between the methyl cation and the methyl anion, and its pyramidal inversion rapidly occurs even at extremely low temperature. From the observation, it is apparent that free radicals are unique and rare species, and are present only under special and limited conditions. However, some of the free radicals are familiar to us in our lives. Thus,

molecular oxygen is a typical free radical, a biradical species. Standard and stable molecular oxygen is in triplet state (3O2), and the two unpaired electrons have the same spin orientation in two orbitals (parallel), respectively, having the same orbital energy, based on hunds rule. Nitrogen monoxide and nitrogen dioxide are also stable, free radical species. Moreover, the reactive species involved in immunity are oxygen free radicals, such as superoxide anion radical (O2-.) and singlet molecular oxygen (1O2). So, free radicals are very familiar to us in our lives and are very important chemicals. Molecular oxygen and nitrogen monoxide are specifically stable free radicals. However, in general radicals are reactive species, and radical coupling reaction, oligomerization, polymerization, etc. occur rapidly, and their control is not so easy. This is one of the main reasons why most organic chemists do not like radical reactions for organic synthesis. However, mild and excellent free radical reactions have recently been established.

FREE RADICAL FORMATIONAtoms are most stable in the ground state. An atom is considered to be "ground" when every electron in the outermost shell has a complimentary electron that spins in the opposite direction. By definition a free radical is any atom (e.g. oxygen, nitrogen) with at least one unpaired electron in the outermost shell, and is capable of independent existence. A free radical is easily formed when a covalent bond between entities is broken and one electron remains with each newly formed atom. Free radicals are highly reactive due to the presence of unpaired electron(s). The following literature review addresses only radicals with an oxygen center. Any free radical involving oxygen can be referred to as reactive oxygen species (ROS). Oxygen centered free radicals contain two unpaired electrons in the

outer shell. When free radicals steal an electron from a surrounding compound or molecule a new free radical is formed in its place. In turn the newly formed radical then looks to return to its ground state by stealing electrons with antiparallel spins from cellular structures or molecules. Thus the chain reaction continues and can be "thousand of events long." The electron transport chain (ETC), which is found in the inner mitochondrial membrane, utilizes oxygen to generate energy in the form of adenosine triphosphate (ATP). Oxygen acts as the terminal electron acceptor within the ETC. The literature suggests that anywhere from 2 to 5% of the total oxygen intake during both rest and exercise have the ability to form the highly damaging superoxide radical via electron escape. During exercise oxygen consumption increases 10 to 20 fold to 35-70 ml/kg/min. In turn, electron escape from the ETC is further enhanced. Thus, when calculated, .6 to 3.5 ml/kg/min of the total oxygen intake during exercise has the ability to form free radicals . Electrons appear to escape from the ETS at the ubiqunone-cytochrome c level. TYPES OF FREE RADICALS Most organic radicals are quite unstable and very reactive. There are two kinds of radicals, neutral radicals and charged radicals as shown below, i.e. a neutral radical , a cation radical and an anion radical . Moreover, there are two types of radicals, the radicals and the radicals. An unpaired electron in the radical is in the orbital, and an unpaired electron in the radical is in the orbital, respectively. Therefore, the radicals and above are radicals. t-Butyl radical is also radical, since this radical is stabilized by the hyperconjugation. However, the phenyl radical and the vinyl radical are typical s radicals.

Normally, radicals are stabilized by the hyperconjugation effect or the resonance effect. However, radicals are very reactive because there is no such stabilizing effectThis result can be explained by the Following fact. The bond dissociation energies of the CH bond in (CH3)3CH (isobutane) and C6H5H (benzene) are ,91 kcal/mol and ,112 kcal/mol, respectively. So, the bond dissociation Energy of the CH bond in benzene is 21 kcal/mol stronger than that in isobutane. This suggests that the phenyl radical is more unstable by about 21 kcal/mol than the tbutyl radical, and thereforeshould be more reactive.

Depiction 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

PROPERTIES OF FREE RADICALS 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 ,-unsaturated compounds (C=CC=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 -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. 1. Combustion Reaction

Probably the most familiar free-radical reaction for most people is combustion. The oxygen molecule is a stable diradical, best represented by O-O, which is stable because the spins of the electrons are parallel. The ground state of oxygen is an unreactive spin-unpaired (triplet) diradical, but an extremely reactive spin-paired (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". 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 is strongly dependent on the concentration of free 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. Propagation or termination reactions can be promoted to alter flammability. Tetraethyl lead was once commonly added to gasoline, because lead itself deactivates free radicals in the gasoline-air mixture. 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. The first thing to form is a

hydroperoxide radical (HOO), which reacts further into hydroperoxides that break up into hydroxide radicals.

Polymerization In addition to combustion, many polymerization reactions involve free radicals. As a result many plastics, enamels, and other polymers are formed through radical polymerization.
STRUCTURE OF FREE RADICALS

Although radicals are generally short-lived due to their reactivity, long-lived radicals exist,

The radical derived from -tocopherol.

and may be categorized as follows: Stable radicals The prime example of a stable radical is molecular dioxygen O2. Organic radicals can be long lived if they occur in a conjugated system, such as the radical derived from -tocopherol (vitamin E). There are also hundreds of examples of thiazyl radicals, which show remarkable kinetic and thermodynamic stability with only a very limited extent of resonance stabilization.[1][2] Persistent radicals Persistent radical compounds are those whose longevity is due to steric crowding around the radical center, which makes it physically difficult for the radical to react with another molecule.[3] Examples of these include Gomberg's triphenylmethyl radical, Fremy's salt (Potassium nitrosodisulfonate, (KSO3)2NO), nitroxides, (general formula R2NO) such as TEMPO, TEMPOL, verdazys, nitronyl nitroxides, and azephenylenyls and radicals derived from PTM (perchlorophenylmethyl radical) and TTM (tris(2,4,6trichlorophenylmethyl radical). The longest-lived free radical is melanin, which may persist for millions of years.[citation needed] Persistent radicals are generated in great quantity during combustion, and "may be responsible for the oxidative stress resulting in cardiopulmonary disease and probably cancer that has been attributed to exposure to airborne fine particles."[4] Diradicals Diradicals are molecules containing two radical centers. Multiple radical centers can exist in a molecule. Atmospheric

oxygen naturally exists as a diradical in its ground state as triplet oxygen. The high reactivity of atmospheric oxygen is due to its diradical state. Interestingly, non-radical states of dioxygen are actually less stable. The relative stability of the oxygen diradical is primarily due to the spin-forbidden nature of the triplet-singlet transition required for it to grab electrons. The diradical state of oxygen also results in its paramagnetic character, which is demonstrated by its attraction to an external magnet.[5]

IMPORTANCE OF FREE RADICAL

Free radicals are naturally produced by some systems within the body and have beneficial effects that cannot be overlooked. The immune system is the main body system that utilizes free radicals. Foreign invaders or damaged tissue is marked with free radicals by the immune system. This allows for determination of which tissue need to be removed from the body. Because of this some question the need for antioxidant supplementation, as they believe supplementation can actually decrease the effectiveness of the immune system.