Purines radicals from

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

The purine radical cations are strong Bronsted acids, and thus rapidly de-protonate in neutral aqueous solutions [47, 48]. For instance, the adenosine radicals generated by reaction with S04 radicals were identified as neutral radicals, A(-H) . A change in pH from 1 to 13 does not affect the transient absorption spectra of these species based on this result, it was inferred that the pKa of A is <1 [49]. The solution pH exerts pronounced effects on the transient absorption spectra of the 2AP radicals assigned to the following equilibrium ... 

The lung also possesses nonenzymatic antioxidants such as vitamin E, beta-carotene, vitamin C, and uric acid. Vitamin E is lipid-soluble and partitions into lipid membranes, where it is positioned optimally for maximal antioxidant effectiveness. Vitamin E converts superoxide anion, hydroxyl radical, and lipid peroxyl radicals to less reactive oxygen metabolites. Beta-carotene also accumulates in cell membranes and is a metabolic precursor to vitamin A. Furthermore, it can scavenge superoxide anion and react directly with peroxyl-free radicals, thereby serving as an additional lipid-soluble antioxidant. Vitamin C is widely available in both extracellular and intracellular spaces where it can participate in redox reactions. Vitamin C can directly scavenge superoxide and hydroxyl radical. Uric acid formed by the catabolism of purines also has antioxidant properties and primarily scavenges hydroxyl radical and peroxyl radicals from lipid peroxidation. 

E. Radicals from Purines, Indolizines, and Cyclazines 1. Purines... 

Purine radical cations are relatively stable, so that the highest intensity ion in the mass spectrum is due to the molecular ion. Subsequent fragmentation depends on the nature of the substituents. The only common fragmentation reaction to all purines appears to be the elimination of HCN from the molecular or fragment ions. Multiple expulsions of HCN also occur as major processes in the mass spectra of a number of purine analogs, including 6-sulfanyl-purine, 7-deazaadenine, or purine itself. ... 

Maki, Y., Makino, X, Hirota, K., and Sako, M., Distinct solvent-dependence in the photoreactions of purine nucleosides with pyrimido[5,4-g]pteridinetetraone N-oxide. Possible generation of hydroxyl radical from the excited N-oxide in alcohols. Heterocycles, 35, 325,1993. 

A different strategy has been applied in our work, that emphasizes the importance of DNA stability on hole transfer within double-stranded DNA. This work is based on determination of the overall yield of oxidized nucleosides that arise from the conversion of initially generated purine and pyrimidine radical cations within DNA exposed to two-photon UVC laser pulses. On the one hand, this work benefits from the excellent current knowledge of chemical reactions involving the radical cations of DNA bases, and on the other hand, from major analytical improvements that include recent availability of the powerful technique of high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (CLHP-ESI-MS/MS) [16-18]. 

The two overwhelming oxidation products of the purine moiety of dGuo 37 arising from the transformation of guanine radical cations 38 were isolated and identified as 2,2-diamino-4-[(2-deoxy-/l-D-eryfhro-pentofura-nosyl)amino]-5(2H)-oxazolone (41) and its precursor 2-amino-5-[(2-deoxy-... 

The primary conclusion that follows from the effect of base sequence on the efficiency of radical cation migration through duplex DNA is that base pairs cannot be considered in isolation. For example, the effect of placing a T in a sequence of purines depends critically on the nature and number of purines. In this regard, the effect of base sequence on radical cation transport emerges from examination of collective properties of the DNA. This is a clear indication that the charge is delocalized over several base pairs, a conclusion that is supported by extensive quantum calculations. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

The hydroxyl radical can also abstract a single electron from dG to generate the base radical cation (G ). In duplex DNA, the G " " will be stabilized by its delocalization into adjacent bases. Both calculations and kinetic measurements " indicate that GG sequences have a lower oxidation potential than an isolated G. Nucleo-bases on the 3 -side of G determine the extent of G formation, and here purines are more effective than pyrimidines at lowering the oxidation potential of G, which accounts for the GG effect and that GA sites are also reactive. ... 

Lipoxygenases (LOX), cycloxygenases (COXs), and xanthine oxidase (XO) are metalloen-zymes whose catalytic cycle involves ROS such as lipid peroxyl radicals, superoxide, and hydrogen peroxide. LOXs and COXs catalyze important steps in the biosynthesis of leuco-trienes and prostaglandins from arachidonic acid, which is an important cascade in the development of inflammatory responses. XO catalyzes the ultimate step in purine biosynthesis, the conversion of xanthine into uric acid. XO inhibition is an important issue in the... 

Although a signal was detected also in irradiated pyrimidine solutions under similar conditions, it was attributed to dissociation products of the pyrimidine molecule and not to photoionization. If the purine solutions contained ethanol, then the signal of the CH3CHOH radical could also be detected this did not happen in ethanolic pyrimidine solutions. The possible importance of photoionization as the primary process in the photochemistry of nucleic acid derivatives has been supported by Kearns, from a study of photoionization in anthracene single crystals.115 He concluded that anthracene photoionization occurred via the interaction of two singlet excitons. 

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