Oxidatively produced DNA damage is a physiological process that has been associated with many human conditions. Of the four DNA bases, guanine is the most easily oxidized and exhibits a large number of oxidation products. The focus of this Microreview is on the structure of the proposed intermediates and final products of guanine oxidation, as determined by spectroscopic methods and independent synthetic studies. The major and minor primary and secondary oxidative DNA lesions that arise from the oxidation of guanine under a variety of conditions, as well as associated structures, are described and all the relevant information regarding the isolation, characterization, and independent synthesis or generation of these lesions in synthetic oligonucleotides is presented. Finally, information on the biological studies that have been advanced, based on the basic molecular information obtained by the aforementioned studies, is provided. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

8-Oxo-7,8-dihydroguanine (8-oxo-G) is the major lesion of oxidatively generated DNA damage. Despite two decades of intense study, several fundamental properties remain to be defined. Its isoelectronic 8-aminoguanine (8-NH(2)-G) has also received considerable attention from a biological point of view, although its chemistry involving redox processes remains to be discovered. We investigated the one-electron oxidation and one-electron reduction reactions of 8-oxo-G and 8-NH(2)-G derivatives. The reactions of hydrated electrons (e(aq)(-)) and azide radicals (N(3)(*)) with both derivatives were studied by pulse radiolysis techniques, and the transient absorption spectra were assigned to specific tautomers computationally by means of time-dependent DFT (TD-B3LYP/6-311G**//B1B95/6-31+G**) calculations. The protonated electron adducts of 8-NH(2)-G and 8-oxo-G showed a substantial difference in their absorption spectra, the unpaired electron being mainly delocalized in the imidazolyl ring and in the six-membered ring, respectively. On the other hand, the deprotonated forms of one-electron oxidation of 8-NH(2)-G and 8-oxo-G showed quite similar spectral characteristics. In a parallel study, the one-electron reduction of 8-azidoguanine (8-N(3)-G) afforded the same transient of one-electron oxidation of 8-NH(2)-G, which represents another example of generation of one-electron oxidized guanine derivatives under reducing conditions. Moreover, the fate of transient species was investigated by radiolytic methods coupled with product studies and allowed self- and cross-termination rate constants associated with these reactions to be estimated.

The atropenantiomers of stable 1,2,3,4-tetrahalo-1,3-butadiene derivatives (where halogeno stands for bromine or iodine) were separated with use of chiral HPLC. The barriers for the enantiomerization process were determined on-line by dynamic HPLC (DHPLC) or off-line by classical kinetic measurements. In the case of the tetrachloro compound, the barrier was too low for DHPLC and its value was obtained by dynamic NMR experiments. The obtained barriers for chloro, bromo, and iodo derivatives correlate with the van der Waals radii of the halogens. The absolute configuration of the isolated enantiomers of the tetraiodo and tetrabromo compounds was assigned by comparison of the experimental and conformations averaged calculated VCD spectra. The identification of a signature band of the absolute configuration of the butadiene core, the sign and location of which are independent from the different conformations and substituents, allowing the safe assignment of the absolute configuration of the enantiomers of chiral 1,3-butadienes, is also reported.

The data concerning the structure, synthesis and reactivity of six-membered ring spiranes exhibiting carbocycles and heterocycles with oxygen atoms are reviewed. The structural aspects are discussed using specific stereogenic elements and stereochemistry descriptors for spiranes with six-membered rings. The data are supported by high field NMR investigations and molecular structures obtained by X-ray diffractometry. The general procedures and access to spiranes with carbocycles and with heterocycles with oxygen are commented.