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The thyminylmethyl radical and the 2′-deoxyuridin-1′-yl radical were studied. The former radical was produced in laser flash photolysis (LFP) studies from two precursors derived from thyminylacetic acid, the N-hydroxypyridine-2-thione ester (PTOC ester), and the phenylselenyl ester. The thyminylmethyl radical has an absorbance in the range 315-340 nm. The rate constant for its reaction with octadecanethiol in THF at ambient temperature determined by LFP methods is (3.1 ( 0.6) × 10 7 M -1 s -1 . The 2′-deoxyuridin-1′-yl radical was produced in bulk photolyses from both diastereomers of the corresponding C1′ tert-butyl ketone, 1′-pivaloyl-2′-deoxyuridine, and in LFP studies from one diastereomer. Trapping of this C1′ radical with 2-mercaptoethanol, cysteine, or glutathione gave both anomers of 2′-deoxyuridine; the product ratios were similar in each case and insensitive to precursor identity or thiol concentrations. Rate constants for reactions of the 2′-deoxyuridin-1′-yl radical with thiols and metal ions were determined by LFP methods; the respective rate constants for reactions with 2-mercaptoethanol, cysteine, glutathione, CuCl 2 , and FeCl 3 in water at ambient temperature are (2.3 ( 0.5) × 10 6 , (2.9 ( 0.4) × 10 6 , (4.4 ( 0.3) × 10 6 , (7.9 ( 0.3) × 10 7 , and ca. 1 × 10 8 M -1 s -1 . The 2′-deoxyuridin-1′-yl radical was addressed computationally. The radical center is not planar, and an energy profile for interconversion of the two anomeric forms of the radical was produced. Computed vertical transitions for the thyminylmethyl radical and one anomer of the 2′-deoxyuridin-1′-yl radical are in good agreement with the experimentally measured UV-visible spectra.

The two diastereomeric forms (5'S) and (5'R) of 5',8-cyclo-2'-deoxyguanosine have been synthesized and fully characterized. They have been used as references for the investigation of gamma-irradiation of 2'-deoxyguanosine and photolysis of 8-bromo-2'-deoxyguanosine in aqueous solutions. The observed (5'R)/(5'S) ratio of 8:1 was obtained in both sets of experiments. The mechanism of the cyclization reaction is discussed in some detail, and the diastereomeric outcome is rationalized in terms of favorable hydrogen-bonded structures in the pro-(5'R) conformation.

Several pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-one ribonucleosides were prepared and tested for antiviral/antitumor activities. Appropriate heterocyclic bases were prepared by standard methodologies. Glycosylation of pyrazoles 6a-e,g,i and of pyrazolo[4,3-d]-1,2,3-triazin-4-ones 12f-1 mediated by silylation with hexamethyldisilazane, with 1-beta-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose, gave in good yields the corresponding glycosides 7a-e,g, 8g,i, 13f,h,k, and 14f, but could not be applied to compounds 12g,i,j,l. To overcome this occurrence, a different strategy involving the preparation, diazotization, and in situ cyclization of opportune pyrazole glycosides 9 and 10 was required. Moreover derivatives having the general formula 5 were considered not only as synthetic intermediates in the synthesis of 3 but also as carbon bioisosteres of ribavirin 4. All compounds were evaluated in vitro for cytostatic and antiviral activity. The pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides that resulted were substantially devoid of any activity; only 15h,k showed a moderate cytostatic activity against T-cells. However, pyrazole nucleosides 9b,c,e were potent and selective cytotoxic agents against T-lymphocytes, whereas 9e showed a selective, although not very potent, activity against coxsackie B1.