The Role of Hydroxyl Radicals

The hydroxyl radical plays two essentially different roles (a) as a reactant mediating the transformations of xenobiotics and (b) as a toxicant that damages DNA. They are important in a number of environments (1) in aquatic systems under irradiation, (2) in the troposphere, which is discussed later, and (3) in biological systems in the context of superoxide dismutase and the role of iron. Hydroxyl radicals in aqueous media can be generated by several mechanisms  

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Van der Zee J, Dubbelman TMAR, Van SteveninckJ (1987) The role of hydroxyl radicals in the degradation of DNA by ozone. Free Rad Res Commun 2 279-284 Vieira AJSC,Telo JP (1997) EPR detection of oxygen radical anion in aqueous solution at room temperature. Redox Rep 3 349-350... 

Que BG, Downey KM, So AG (1980) Degradation of deoxyribonucleic acid by a 1,10-phenanthroline-copper complex the role of hydroxyl radicals. Biochemistry 19 5987-5991 Quintiliani M (1983) Cellular thiols and radiation response. In Balzani V (ed) Baxendale Memorial Symposium. Lo Scarabeo, Bologna, pp 81-108... 

J. Hoigne and H. Bader, The Role of Hydroxyl Radical Reactions in Ozonation Processes in Aqueous Solutions, Water Res, 10(377) (1976). 

The role of hydroxyl radicals in these ring and inter unit cleavage react ion s has been confirmed by adding peroxide stabilizers. When sodium silicate was present there was no reaction with either simple phenol model compounds or guaiacylglycerol-p-guaiacyl ether (Figure 12.1, Ila) [28,30,31]. 

Hoigne J. and Bader H., The role of hydroxyl radical reaction in ozonation processes in aqueous solution . Water research, 10, 377. (1976)... 

EPR has been used in studies of the role of hydroxyl radicals and their role in the toxicity of H202 to bacteria. In a study directed to the analysis of the role of Fe and the generation of H202 in E. coli (McCormick et al. 1998), hydroxyl radicals were specifically trapped by reaction with ethanol to give the a-hydroxyethyl radical that then forms a stable adduct with a-(4-pyridyl-l-oxide)-/V-f-butyl nitroxide (stable adducts are not formed either by superoxide or hydroxyl radicals). The role of redox-reactive iron used EPR to analyze the EPR-detectable ascorbyl radicals. 

Kanno T, Nakamura K, Ikai H, Kikuchi K, Sasaki K, Niwano Y (2012) Literature review of the role of hydroxyl radicals in chemically-induced mutagenicity and carcinogenicity for the risk assessment of a disinfection system utilizing photolysis of hydrogen peroxide. J Clin Biochem Nutr 51 9-14... 

Lelieveld J, Dentener F, Peters W, Krol MC (2004) On the role of hydroxyl radicals in the self cleansing capacity of the troposphere. Atmos Chem Phys 4 2337-2344... 

Hoehn RC, Rosenblatt AA, Gates DJ (1996) AWWA water quality technology conference, Boston Hoigne J, Bader H (1976) The role of hydroxyl radical reactions in ozonation processes in aqueous solutions. Water Res 10(5) 377-386... 

However, subsequent studies demonstrated that the formation of hydroxyl radicals, even if it takes place during lipid peroxidation, is of no real importance. Beloqui and Cederbaum [11] have found that although the glutathione-glutathione peroxidase system suppressed hydroxyl radical generation during the oxidation of 4-methylmercapto-2-oxo-butyrate, it exhibited a much smaller effect on microsomal lipid peroxidation. Therefore, hydroxyl radical formation is apparently unimportant in this process. Other authors also pointed out at an unimportant role of hydroxyl radicals in the initiation of microsomal lipid peroxidation [12 14], For example, it has been shown that Fe(EDTA), a most efficient catalyst of hydroxyl radical formation by the Fenton reaction, inhibited microsomal and liposomal lipid peroxidation, while the weak catalysts of this reaction Fe(ADP) and Fe(ATP) enhanced it [13]. 

Biaglow JE, Kachur AV (1997) The generation of hydroxyl radicals in the reaction of molecular oxygen with polyphosphate complexes of ferrous ion. Radiat Res 148 181-187 Biaglow JE, Field KD, Manevich Y, Tuttle S, Kachur A, Uckun F (1996) Role of guanosine triphosphate in ferric ion-linked Fenton chemistry. Radiat Res 145 554-562 Bielski BHJ (1991) Studies of hypervalent iron. Free Radical Res Commun 12/13 469-477 Bielski BHJ, Allen AO, Schwarz HA (1981) Mechanism of disproportionation of ascorbate radicals. J Am Chem Soc 103 3516-3518... 

Panganamala, R.V., Sharma, H.M., Heikki, J.C., Geer, J.C., and Cornwell, D.G. 1976. Role of hydroxyle radical scavenger dimethylsulfoxide, alcohols and methional in the inhibition of prostaglandin biosynthesis. Prostaglandins 11, 599. 

The presence of hydroxyl radical scavengers also plays a key role in the overall fate of the peroxide. Scavenging of hydroxyl radical minimizes the occurrence of reactions (5), (6), and (11). Organic scavengers generally react with hydroxyl radical in one of the two following types of reactions ... 

As previously discussed, the concentration of Fe2+ is an important factor in the rate of hydroxyl radical formation from hydrogen peroxide. Consequently, any process that can speed the reduction of Fe3+ to Fe2+ will increase the formation rate of hydroxyl radical. UV or visible radiation can play this role by photoreducing iron. However, the photo-Fenton process involves three additional mechanisms that can contribute to pollutant degradation (a) direct photolysis of H202 to yield two hydroxyl radicals (Eq. (22)) (b) photolysis of Fe(OH)2+ to form hydroxyl radical (Eq. (23)) and (c) degradation of pollutants by direct photolysis (i.e., absorption of a photon by the pollutant molecule followed by decomposition of the photoexcited pollutant molecule). 

Recent reports show unexpected information on the role of free radicals in the health effects of nanotubes currently employed in many industries.31 Unlike asbestos and most toxic particles, nanotubes do not release but blunt free radicals, which are considered one of the features imparting toxicity to particulates. Multi-wall carbon nanotubes (MWCN) in aqueous suspension do not generate oxygen or carbon centered free radicals detectable with the spintrapping technique. Conversely, when in contact with an external source of hydroxyl (HO) or superoxide radicals (CL h MWCN exhibit a remarkable radical scavenging capacity (Figure 3). It is therefore possible that the inflammatory reaction reported in vivo should be ascribed to MWCN features other than particle derived free radical generation. 

To assess the damaging role of hydroxyl radical generation in in vitro systems it is obviously important to be able to detect, identify and quantitate it accurately. Since hydroxyl radical generation in vivo has... 

In contrast to the water phase the HO radicals can have a much longer lifetime in gaseous media, i.e. up to 1 s for the OH and 60 s for the HO radical, respectively (Fabian, 1989). Despite the low concentration of OH radicals of about 10 molecules per cm in the sunlit troposphere (Ehhalt, 1999) they play an important role in controlling the removal of many organic natural and manmade compounds from the atmosphere (Eisele et al., 1997, Eisele and Bradshaw, 1993). Even in indoor environments, the formation of hydroxyl radicals is possible by ozone/alkene reactions (Atkinson et al., 1995). Steady-state indoor hydroxyl radical concentrations of about 6.7x10 ppb equivalent to 1.7x10 molecules cm were calculated at an ozone concentration of 20 ppb (Weschler and Shields, 1996). 

The central role of hydroxyl radicals in atmospheric chemistry is well illustrated by examining the atmospheric cycles of methane and carbon monoxide. A quantitative assessment of both of these species was carried out in the 1920s in Belgium by Marcell Migeotte, who detected their absorption lines in the spectrum of infrared solar radiation reaching Earth s surface. 

The examples of hydroxyl radical addition products identified in single crystals of adenine and guanine base derivatives confirm that water can play an important role in the radiation damage mechanism. It should be noted that the new mechanism has attracted some criticism [38]. The main objection is that nonplanar geometries were calculated for the gas phase radicals whereas planar structures are expected experimentally due to the hydrogen-bonding scheme... 

Muller M, and Sorrell TC. (1997). Oxidative stress and the mobilisation of arachidonic acid in stimulated human platelets role of hydroxyl radical. Prostaglandins 54,493-509. 

For the sake of completeness, attention is drawn to the following (1) the interactive role of hydroxyl radicals, superoxide, and Fe levels in wild and mutant strains of Escherichia coli lacking Fe and Mn superoxide dismutase is discussed in Sections 5.2.4 and 5.5.5 and (2) the possible role of hydroxyl radicals in mediating the transformations accomplished by the brown-rot fungus Gleophyllum striatum which is supported by the overall similarity in the structures of the fungal metabolites with those produced with Fenton s reagent (Wetzstein et al. 1997). 

Analytical procedures for hydroxyl radicals noted in Section 2.3 and have been used to demonstrate the role of the anticancer drug 2,5-bis(l-azacyclo-propyl)-3,6-bis(carboethoxyamino)benzo-l,4-quinone in mediating the production of hydroxyl radicals in JB6 mouse epidermal cells (Li et al. 1997). 

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