Radicals H-adduct

In this context it is worth considering that in the free-radical chemistry of DNA the C(6)- OH-adducts radicals are certainly of a greater importance than the C(6)-H-adduct radicals investigated here. If the benzene system is a good guide H02--elimination from hydroxycyclohexadienylperoxyl radicals is noticeably slower than that from cyclohexadienylperoxyl radicals (Pan et al. 1993a), i.e., the rate of H02--elimination from 5,6-dihydro-6-hydroxy-thymidine-5-per-oxyl radicals may even be slower. 

Radiolytic spin labeling of molecules adsorbed in zeolites occurs by ionization to form radical cations and by formation of H-adduct radicals by H atom addition. Ionization of adsorbed molecules is a two-step process, equations (1) and (2). Because the adsorbate loading used in experiments is low (typically one percent or less by weight), energy is absorbed by the matrix and not directly by the adsorbate. Holes (Z" ) created in the zeolite lattice migrate to adsorbate (A) by charge transfer. Stabilization of radical cations is made possible at low temperature by sequestration in the zeolite pores and by trapping of electrons by the matrix. 

In guanosine after the rapid protonation of the electron adduct by water [86, 88] at the heteroatom [at O , N 3) or N(7) k > lO s ], a rapid transformation occurs which is catalysed by phosphate buffer and which has been attributed to a protonation at C(8) [88]. This assignment is based upon solid-state EPR data [91], where the C(8)-H-adduct radical appears as the thermodynamically most stable H-adduct radical. The high solvent-kinetic-isotope effect of kn/ki) = 8 is a strong indication that a proton is transferred in the rate-determining step. The magnitude of the rate of phosphate buffer catalysis points to a protonation at carbon (for a similar reaction observed with the thymine radical anion see above). Other purines, e.g. hypoxanthine/inosine, behave in a similar way [89]. 

Figure 6 Electron affinities and ionization potentials of the DNA base OH and H adduct radicals calculated by scaling the Koopmans EAs and Koopmans IPs to experiment. These scales represent estimated vertical EAs and IPs. Double headings on the IP scale correspond to species with equal ionization potentials. Radical with electron affinities above 1.4eV are predicted to undergo reduction by thiols. Reproduced with piermission from ref. [145].

Iron(II) salts, usually in conjunction with catalytic amounts of copper(II) compounds, have also been used to mediate radical additions to dienes91,92. Radicals are initially generated in these cases by reductive cleavage of peroxyesters of hydroperoxides to yield, after rearrangement, alkyl radicals. Addition to dienes is then followed by oxidation of the allyl radical and trapping by solvent. Hydroperoxide 67, for example, is reduced by ferrous sulfate to acyclic radical 68, which adds to butadiene to form adduct radical 69. Oxidation of 69 by copper(H) and reaction of the resulting allyl cation 70 with methanol yield product 71 in 61% yield (equation 29). 

This quinone reacts in aqueous solution with OH and H adducts of cytosines and uracils by an electron transfer/addition mechanism, similar to Eq. 18 [28], Addition takes place at the quinone carbonyl oxygen to produce an anthroxyl radical. This then undergoes spontaneous C-O heterolysis ... 

As an example, the propagation steps for the reductive alkylation of alkenes are shown in Scheme 7.1. For an efficient chain process, it is important (i) that the RjSi radical reacts faster with RZ (the precursor of radical R ) than with the alkene, and (ii) that the alkyl radical reacts faster with the alkene (to form the adduct radical) than with the silicon hydride. In other words, the intermediates must be disciplined, a term introduced by D. H. R. Barton to indicate the control of radical reactivity [5]. Therefore, a synthetic plan must include the task of considering kinetic data or substituent influence on the selectivity of radicals. The reader should note that the hydrogen donation step controls the radical sequence and that the concentration of silicon hydride often serves as the variable by which the product distribution can be influenced. 

Some other interesting observations regarding free radicals in these systems are noteworthy. In many instances, multiple conformations of radicals are found at lower but not higher temperatures. This indicates that the radicals exist in shallow energy wells at low temperature this phenomenon was observed very early, in the 4 K ENDOR investigation of radical formation in amino acids.23 Unlike the process in DNA. In which it is well understood that the thymine anion radical protonates at C6 to form T(C6)H-, in the crystalline state there is a not clear link between pyrimidine electron adducts and H-addition radicals. We finally note that a deuterium isotope effect of protonation/deprotonation processes was found in cytosine.HCl and 2 -deoxycytidine.HCl, as evidenced by a lower propensity for these processes to occur in partially deuterated systems than in predated ones. 

The rate of fluorine displacement from fluorotoluenes by H-atoms has been measured in single-pulse shock tubes at 988-114 K.158 The addition of CF3 to CgFsCl has been studied.159 The intermediate adduct radical (CF3C6F5C1) was shown to react with an additional CF3 to give CF3CI and C6F5CF3. A range of fluorinated biphenyls can be produced by the reaction of pentafluorobenzene radicals with both electron-rich and -poor aromatics. The isomeric ratios of biphenyls produced indicated an efficient homolytic chain process.160... 

The phosphate-adduct radical is also formed, when the reaction is initiated by S04 [reaction (18)] in the presence of phosphate ions (Behrens et al. 1988). This may either be due to an Sn2 substitution reaction [reaction (19)] or a reaction of the phosphate ion with the radical cation [reaction (17)] formed either by an elimination of S042- plus H+ [reaction (20)] and subsequent protonation of the N(3)-centered radical [equilibrium (22)] or by S042- elimination [reaction (21)], as envisaged originally. The reaction of the radical cation with phosphate would then give rise to the observed radical [reaction (23)]. 

On the other hand, the C(6)- OH-adduct formed in reaction (61) has oxidizing properties (note its mesomeric form with the radical at oxygen quantum-mechanical calculations indicate that it is the most oxidizing radical among all conceivable OH- and H-adducts of the nudeobases Colson and Sevilla 1995). The yield of this oxidizing radical can be determined with the help of a strong re-ductant such as TMPD [reaction (63) the TMPD radical cation is monitored e(565 nm) = 12,500 dm3 mol-1 cm-1]. 

Photolysis of 5,6-dihydro-5-selenophenyl-dTyd (Tallman et al. 1998) also affords the C (6) H -adduct, and in the presence of 02 the corresponding peroxyl radical [reactions (170) and (171)]. The latter may undergo H02 -elimination giving rise to Thd [reaction (172)] or, in the presence of tributyltinhydride, yields 5,6-dihydro-5-hydroxy-dTyd [reaction (173)]. The ratio of these two products depends on the tributyltinhydride concentration, and from such data the ratio of the rate constants of reactions (172) and (173) has been calculated at 1.3 x 10 2 mol dm-3. 

The mechanism presented here is somewhat at variance with that proposed by the authors (Yamamoto et al. 1995) who suggested that the /BuOI I-derived radical adds to the primarily formed electron-adduct radical. Since this has been shown above to have only a very short lifetime, it will not be capable of undergoing bimolecular recombination reactions. An isomerization of C(8)-H -adduct [reaction (183)] followed by an addition of the tert-butanol-derived radical and water elimination [reactions (184) and (185)] is not in conflict with the above pulse radiolysis results [note that the tautomerization reaction (183) cannot be excluded on the basis of the pulse radiolysis data]. 

Whenever H--adducts are observed, they must not necessarily have H- as precursor. Protonation of the radical anion must always be considered as an alter-native/additional route. In crystals, the radical cations may serve as the proton source, while in frozen aqueous solutions the solvent will provide the proton. 

Single-crystals and powders. In Ura, the N(l)-centered radical is observed (Zeh-ner et al. 1976). Based on our present knowledge, one may suggest that it arises most likely from the deprotonation of the radical cation. The radical anion is protonated at 0(4). The C(5) -TP-adduct primarily formed is converted with light of A > 400 nm into the thermodynamically more stable C(6)-H -adduct [reaction (303)]. This is also observed with other pyrimidines (Flossmann et al. 1976). 

In IMeUra, a predominating radical is the -CH2 radical (Flossmann et al. 1973, 1975a,b). A -CH2 radical (here, allylic) is also observed with Thy and 5MeCyt (Hiittermann 1970 Hiittermann et al. 1971 Dulcic and Herak 1973). Radical cations are likely precursors, while the precursor of the Thy C(6)-H--adduct that is commonly observed (Henriksen and Snipes 1970) could be the Thy radical anion (Symons 1990 see above). 

The ENDOR technique applied to an X-irradiated dAdo single-crystal allowed a complete analysis of the EPR parameters of the major radicals formed in that system (Nelson et al. 1998). The hole deprotonates at N(6) while the electron gain center protonates at N(3) -H-adducts are formed at C(2) and C(8). The thermodynamically more stable radical is the C(8) -H-adduct (see above), but in Ade light can convert the C(8) H-adduct into the C(2) -H-adduct [Zehner et al. 1977 reaction (304)]. 

Candeias LP, Steenken S (2000) Reaction of HO with guanine derivatives in aqueous solution formation of two different redox-active OH-adduct radicals and their unimolecular transformation reactions. Properties of G(-H) Chem Eur J 6 475-484... 

Deeble DJ, von Sonntag C (1985) TheUV absorption spectra of theC(5) and C(6) OH adduct radicals of uracil and thymine derivatives. A pulse radiolysis study. Z Naturforsch 40c 925-928 Deeble DJ, von Sonntag C (1987) Radioprotection of pyrimidines by oxygen and sensitization by phosphate a feature of their electron adducts. Int J Radiat Biol 51 791-796 Deeble DJ, Das S, von Sonntag C (1985) Uracil derivatives sites and kinetics of protonation of the radical anions and the UV spectra of theC(5) and C(6) H-atom adducts. J Phys Chem 89 5784-5788... 

It is reasonable to assume that the H-- and -OH-adducts at C(5) of C bind to C(8) of the neighboring G, and the resulting adduct radical is oxidized in subsequent free-radical termination reactions. While the H--adduct product (on the right)... 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

Photohydroalkylations are in most cases carbon-centered radical conjugate additions onto electron-deficient olefins [7]. Scheme 3.3 summarizes in detail the pathways for the photogeneration of radicals from R-H(Y) 1. In path a, a photocatalyst P (when excited) cleaves homolytically a suitable C—H bond, and the resultant radical adds to the olefin 2 to form the adduct radical 3. a,(3-Unsaturated nitriles, ketones, and esters... 

Radicals of the cyclohexadienyl type show moderately intense peaks at 300-350 nm (e 3000-4000 M -1 cm-1). Radicals of this type are produced by addition of H or OH to benzene and its derivatives, and their spectral parameters are affected by the substituent. In general, it is found that both the OH and H adducts have very similar absorption spectra and extinction coefficients. The electron adducts usually absorb at somewhat lower wavelengths. The effects of substituents on the absorption maxima, as expressed by the bathochromic shifts [( ArH — Arx)IvAth where v is the wave... 

H atoms (H ) tend to abstract hydrogen atoms from C-H bonds, particularly if these are activated by neighboring functionalities such as sulfur atoms. The sulfur atom in thioethers was not usually considered as the primary target of H atom despite some, mostly recent, reports showing that bimolecular homolytic substitutions with H atom might occur with thioethers. Because these sulfur atoms are hypervalent, they can form adducts with H atoms. Radical chemistry studies on 1,3,5-trithiane (1,3,5-TT), performed by pulse radiolysis,... 

Similar to Cyt, the purine radical anions are also rapidly protonated by water [cf. reaction (15)]. The primary H adducts thus formed rmdergo a series of tautomerization reactions, eventually reaching thermodynamically more favorable H adducts [cf. reactions (16) and (17)]. ... 

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