Generation of free radicals

The dissociation energies of C-C, C-H, C-0 and C-X bonds are quite high, but the very weak 0-0 bonds of peroxides are cleaved at relatively low temperatures (Table 2.2). 

Organic azo compounds (R-N=N-R) also easily decompose to alkyl radicals and nitrogen. The thermodynamic stability of nitrogen provides an overall driving force for this decomposition. Homolysis of several weaker bonds initiates the carbon radical reactions 

Bond D(kcalmol ) T(°C) Bond Dfkcalmol ) TCO Bond D(kcalmol ) r(°c) 

Following are some of the methods used for the generation of free radicals. 

Cu also finds application in the Sandmeyer reaction involving the decomposition of diazonium salts. In this reaction the free radical Ar is formed as an intermediate. 

The halogens are quite readily homolyzed by light. The 58kcal mol required to break the Cl-Cl bond is furnished by light, which is absorbed. The energy of a quantum of light depends on the wavelength and can be derived from a simple formula (Eq. (4.2))  

Radicals may also result from chemical or electrochemical oxidation or reduction of stable molecules. Single-electron transfer processes initially generate radical cations (for oxidation) or radical anions (for reduction), which may then fragment to radicals and ions. For example, Sargent and coworkers determined that in 1,2-dimethoxyethane solutions the radical anion of naphthalene (sodium naph-thalenide, Na Ar ) transferred an electron to propyl iodide. Subsequent loss of 

There are several reactions that are used frequently to generate free radicals, both to study radical structure and reactivity and in synthetic processes. Some of the most general methods are outlined here. These methods will be encountered again when we discuss specific examples of free radical reactions. For the most part, we defer discussion of the reactions of the radicals until that point. 

Peroxides are a common source of radical intermediates. Commonly used initiators include benzoyl peroxide, f-butyl peroxybenzoate, di-f-butyl peroxide, and r-butyl hydroperoxide. Reaction generally occurs at relatively low temperature (80° -100°C). The oxygen-oxygen bond in peroxides is weak ( 30kcal/mol) and activation energies for radical formation are low. Dialkyl peroxides decompose thermally to give two alkoxy radicals.  

Diacyl peroxides are sources of alkyl radicals because the carboxyl radicals that are initially formed lose CO2 very rapidly. In the case of aroyl peroxides, products can be derived from either the carboxyl radical or the radical formed by decarboxylation. The decomposition of peroxides can also be accomplished by photochemical excitation. 

Peroxyesters are also sources of radicals. The acyloxy portion normally loses carbon dioxide, so peroxyesters yield an alkyl (or aryl) and alkoxy radical.  

The thermal decompositions described above are unimolecular reactions that should exhibit first-order kinetics. Peroxides often decompose at rates faster than expected for unimolecular thermal decomposition and with more complicated kinetics. This behavior is known as induced decomposition and occurs when part of the peroxide decomposition is the result of bimolecular reactions with radicals present in solution, as illustrated specifically for diethyl peroxide. 

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He/minthosporium (15). The mode of action is considered to be inhibition of the enzyme NADPH-cytochrome C reductase, which results in the generation of free radicals and/or peroxide derivatives of flavin which oxidize adjacent unsaturated fatty acids to dismpt membrane integrity (16) (see Enzyme inhibitors). 

Primary and secondary dialkyl peroxides undergo thermal decompositions more rapidly than expected owing to radical-induced decompositions (73). Such radical-induced peroxide decompositions result in inefficient generation of free radicals. 

This catalyst system is temperature-sensitive and does not function effectively at temperatures below 10°C but at temperatures over 35°C the generation of free radicals can be too prolific, giving rise to incomplete cross-linking formation. Redox systems are preferred for fabrication at temperatures ranging from 20—30°C (Fig. 5). 

KAGAN-MOLANDER Samanum reagent Lanthanide reagents, speoflcally samanum, lor generation of free radicals useful in cyclizations, reductions... 

The principal components of atmospheric chemical processes are hydrocarbons, oxides of nitrogen, oxides of sulfur, oxygenated hydrocarbons, ozone, and free radical intermediates. Solar radiation plays a crucial role in the generation of free radicals, whereas water vapor and temperature can influence particular chemical pathways. Table 12-4 lists a few of the components of each of these classes. Although more extensive tabulations may be found in "Atmospheric Chemical Compounds" (8), those listed in... 

The generation of free radicals usually does not immediately start polymerization in commercial adhesives. These contain small amounts of inhibitors, which are chemical compounds that prevent free radical polymerization. Inhibitors are purposely added to acrylic adhesives to obtain practical shelf life. Inhibitors stop polymerization by reacting with active free radicals to form a less reactive species... 

The early work of Kennerly and Patterson [16] on catalytic decomposition of hydroperoxides by sulphur-containing compounds formed the basis of the preventive (P) mechanism that complements the chain breaking (CB) process. Preventive antioxidants (sometimes referred to as secondary antioxidants), however, interrupt the second oxidative cycle by preventing or inhibiting the generation of free radicals [17]. The most important preventive mechanism is the nonradical hydroperoxide decomposition, PD. Phosphite esters and sulphur-containing compounds, e.g., AO 13-18, Table la are the most important classes of peroxide decomposers. 

The species (M)S- -Me(CO)n-i arises from Eq. (7) and reacts with suitable halides (e.g., CCI4) with a generation of free radicals ... 

In the presence of radical initiators such as benzoyl peroxide (BPO), azobisisobutyronitrile (AIBN), persulfates (S208 ), etc., grafting of vinyl monomers onto polymeric backbones involves generation of free radical sites by hydrogen abstraction and chain transfer processes as described below ... 

The effect of Fe(II) on grafting of 2-hydroxyethyl methacrylate onto polyester fibers in the presence of benzoyl peroxide was investigated [59]. It was found that increasing the iron ion concentration decreases the graft yield. This suggest that excess Fe(ll) ions participate in the generation of free radical species and the iron ions seem to contribute to the termination and, consequently, decrease the graft yield. 

Ionizing radiation is unselective and has its effect on the monomer, the polymer, the solvent, and any other substances present in the system. The radiation sensitivity of a substrate is measured in terms of its G value or free radical yield G(R). Since radiation-induced grafting proceeds by generation of free radicals on the polymer as well as on the monomer, the highest graft yield is obtained when the free radical yield for the polymer is much greater than that for the monomer. Hence, the free radical yield plays an important role in grafting process [85]. 

Equation (l) shows the rate of polymerization is controlled by the radical concentration and as described by Equation (2) the rate of generation of free radicals is controlled by the initiation rate. In addition. Equation (3) shows this rate of generation is controlled by the initiator and initiator concentration. Further, the rate of initiation controls the rate of propagation which controls the rate of generation of heat. This combined with the heat transfer controls the reaction temperature and the value of the various reaction rate constants of the kinetic mechanism. Through these events it becomes obvious that the initiator is a prime control variable in the tubular polymerization reaction system. 

In addition to heat and light, generation of free radicals can be accomplished by using 7-rays, X-rays or through electrochemical means. In general, however, these methods do not tend to be so widely used as those involving benzoyl peroxide or AIBN as initiators. 

Hydroperoxidases protect the body against harmful peroxides. Accumulation of peroxides can lead to generation of free radicals, which in turn can dismpt membranes and perhaps cause cancer and atherosclerosis. (See Chapters 14 and 45.)... 

Peroxidation of lipids containing polyunsaturated fatty acids leads to generation of free radicals that may damage tissues and cause disease. 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

Finally, AIDS dementia has parallels with cerebral ischemia or stroke and again the key mechanism appears to involve overactivation of glutamate receptors, in particular the NMDA receptor, followed by excessive influx of calcium and the generation of free radicals. 

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

X-Ray irradiation of quartz or silica particles induces an electron-trap lattice defect accompanied by a parallel increase in cytotoxicity (Davies, 1968). Aluminosilicate zeolites and clays (Laszlo, 1987) have been shown by electron spin resonance (e.s.r.) studies to involve free-radical intermediates in their catalytic activity. Generation of free radicals in solids may also occur by physical scission of chemical bonds and the consequent formation of dangling bonds , as exemplified by the freshly fractured theory of silicosis (Wright, 1950 Fubini et al., 1991). The entrapment of long-lived metastable free radicals has been shown to occur in the tar of cigarette smoke (Pryor, 1987). 

The major limitation of nitrate therapy is the development of tolerance with continuous use. The loss of anti-anginal effects may occur within the first 24 hours of continuous nitrate therapy. While the cause of tolerance is unclear, several mechanisms have been proposed. These include depletion of the sulfhydryl groups necessary for the conversion of nitrates to nitric oxide, activation of neurohormonal systems, increased intravascular volume, and generation of free radicals that degrade nitric oxide. The most effective method to avoid tolerance and maintain the anti-anginal efficacy of nitrates is to allow a daily nitrate-free interval of at least 8 to 12 hours. Nitrates do not provide protection from ischemia during the nitrate-free period. Therefore, the nitrate-free... 

Enhanced generation of free radicals due to some catalysts such as FeSC>4 or elemental iron. 

The main feature of the PCL measuring method is combination of the simple and reliable photochemical generation of free radicals with their very sensitive... 

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