Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2'-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2:1 water:acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines for this coupling reaction. The coupling chemistry has been extended to 8-bromo-2'-deoxyadenosine (8-BrdA) and 5-iodo-2'-deoxyuridine (5-IdU), as well as the ribonucleosides 8-bromoguanosine and 8-bromoadenosine. Good to excellent yields of arylated adducts are obtained in all cases. With use of tri(4,6-dimethyl-3-sulfonatophenyl)phosphine (TXPTS), the Suzuki coupling of 8-BrdA and 5-IdU can be accomplished in less than 1 h at room temperature. This methodology represents an efficient and general method for halonucleoside arylation that does not require prior protection of the nucleoside.

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Incubation of Cr(VI) with ascorbate generated Cr(V), Cr(IV) and ascorbate-derived carbon-centered alkyl radicals, as well as formyl radicals. H2O2 caused generation of hydroxyl radicals (OH) and much higher levels of Cr(V), showing that .OH can be generated via a Cr(IV)-mediated Fenton-like reaction (Cr(IV) + H2O2-->Cr(V) + .OH + OH-). 1,10-Phenanthroline and deferoxamine inhibited the formation of both .OH and Cr(V) from the reaction of Cr(VI) with ascorbate in the presence of H2O2. Electrophoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. .OH radicals generated by Cr(V)- and Cr(IV)-mediated Fenton-like reactions also caused DNA double-strand breaks. HPLC measurements showed that .OH radicals generated by Cr(IV) and Cr(V) from H2O2 caused 2'-deoxyguanine hydroxylation to form 8-hydroxy-2'-deoxyguanine.

21 (26 mg, 39%) were separated by preparative TLC (C) and identified by comparison with authentic materials, prepared according to Le Men et al.26 X-ray Structure Determination. (A) Zwitterion 7a Hydrate (XR-1). Single crystals of XR-1 suitable for X-ray diffraction study were grown from a saturated MeOH solution. The structure was solved by direct methods (program multan so): the "best" E-map allowed to localize 27 heavy atoms over a total of 32. The remaining heavy atoms were located on a difference Fourier map. After isotropic refinement of heavy atoms, all hydrogen atoms, with the exclusion of those of solvation water, were located on a difference Fourier map. Hydrogen atoms at C(18) and C(25) gave problems in the least-squares process and then were fixed in calculated positions. Hydrogen atoms of solvated water were not clearly localized, because of the high thermal internal motion or the disorder of the same.(B) Isoxazolidine 8b Hydrobromide (XR-2). Single crystals of XR-2 were obtained by diffusion of diisopropyl ether into a saturated MeOH solution of 8b-HBr. The structure was solved