Sugars Radicals

Under low oxygen conditions, C5 -sugar radicals can react with the base residue on the same nucleotide. In purine nucleotides, the carbon-centered radical 91 can add to the C8-position of the nucleobase (Scheme 8.31). Oxidation of the intermediate nucleobase radical 92 yields the 8,5 -cyclo-2 -deoxypurine lesion 93197,224,225,230-233 Similarly, in pyrimidine nucleotides, the C5 -radical can add to the C6-position of nucleobase. Reduction of the resulting radical intermediate yields the 5, 6-cyclo-5,6-dihydro-2 -deoxypyrimidine lesion 94,234-236... 

Scheme 1 Generation of guanine radical cation 4 and sugar radical cation 7...

Scheme 3 Charge transfer from the sugar radical cation to guanine (G)... 

It would be interesting to test with other Rh(III) complexes, whether the direct oxidation of the base (by photo-electron transfer) could also be a primary step responsible for photocleavages. Indeed, as outlined before in Sect. 5, radiation studies have shown that the radical cation of the base can produce the sugar radical, itself leading to strand scission [122]. Moreover base release, as observed with the Rh(III) complexes, can also take place from the radical cation of the base [137]. Direct base oxidation and hydrogen abstraction from the sugar could be two competitive pathways leading to strand scission and/or base release. 

Some time ago, an allyl-like radical was observed in irradiated crystals of 5 -dCMP [26]. This radical was thought to be a sugar radical, although no likely scheme was proposed for its formation. It now appears that this radical is formed on 5-methyl cytosine impurities in these crystals [27]. This radical forms by deprotonation at the methyl group of the cytosine cation, 5meCyt(Me—H) , and may have important consequences in the radiation chemistry of DNA since the ionization potential of 5-methyl cytosine is lower than that of either cytosine or thymine. 

More recently, this same group has studied DNA with high-field EPR (245 GHz) [51]. This study shows nice spectra of the Thy(Me—H) radical. Also, the authors discuss the effects of hydration levels on the production of the various base radicals. A more recent paper by Weiland and Hiittermann [52] considers the same base radicals in DNA at 77 K and then looks at the transformation of these radicals into the more stable room-temperature products. Among these are Cl and C3 sugar radicals, dRib(Cl —H), and dRib(C3 -H) , respectively. 

Thus we find that the hole is deeply trapped by two distinctly different mechanisms. One that requires no activation energy, sugar radical formation occurs even at 4 K, and the other that does, HO addition to the guanine radical cation. Similarly, the excess electron is irreversibly trapped by two distinct mechanisms, one that is activated and the other which is not. 

Radical 15, C4 (-H) , could be only tentatively identified. ENDOR spectra indicated that it was present in two slightly different conformations at 10 K. At 150 K, the ENDOR line associated with the 2.89 mT coupling decreased in intensity and that associated with the 2.80 mT line increased, indicating the radical relaxes into a more stable conformation at 150 K. A variety of small couplings were observed, but not characterized, in both conformations of 15. An unidentified likely sugar radical was detected in 2 -deoxycytidine hydrochloride through observation, in both deuterated and undeuterated crystals, of a nearly axially symmetric 0-type coupling with Aiso = 3.21 mT. It appears to exist in three different conformations at 10 K at 150 K, one of these conformations seems to disappear, and two appear to increase in concentration. 

Analogous addition of a sugar radical to an unsaturated sulfone has been described by the same authors in the course of pseudomonic acid synthesis. For this, UV irradiation of the iodosugar was used to generate a secondary radical [120],... 

Oxidation of Nucleobase/Sugar Radicals by Radiation Sensitizers 301... 

Photolysis of G + leads to the formation of sugar radicals (Adhikary et al. 2005). Product studies from solid state irradiation of Thd are also available (Gromova et al. 1999). As discussed above, the Thd radical cation is expected to deproton-ate at N(3) and at methyl, and the ensuing structural elements indeed dominate the product spectrum parts of which is shown below. 

Parr KD, Wetmore SD (2004) The properties of DNA C4 -centered sugar radicals the importance of the computational model. Chem Phys Lett 389 75-82 Patterson LK, Bansal KM (1972) Pulse radiolysis studies of 5-halouracils in aqueous solutions. J Phys Chem 76 2392-2399... 

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