Characterization of γ-Radiation Induced Decomposition Products of Thymidine-Containing Dinucleoside Monophosphates by Nuclear Magnetic Resonance Spectroscopy

Abstract

To study the chemical and biochemical influence of loss of base aromaticity, dinucleoside monophosphates containing cis-5R, 6S-thymidine glycol (T^g) and 5R and 5S 5, 6-dihydrothymidine (T^h) were prepared from d-ApT and d-TpA by KMnO₄ oxidation and rhodium-catalysed hydrogenation, respectively. One and two dimensional ¹H NMR techniques were used to characterize the solution conformation of each of the modified dinucleoside monophosphates for comparison with the unmodified compounds. Coupling constant data show that all sugar moieties adopt a predominantly 2′-endo conformation. Estimates of proton-proton distances from two-dimensional NOE experiments reveal that most of the glycosidic bonds prefer the anti conformation. Analysis of the C5′-C4′ (γ) torsion angle of the hydroxymethyl group using ³J_H4′H5′ and ³J_H4′H5″ data indicate that these modifications to thymine have little effect on they conformer populations. Although, in general, additions at C5 and C6 of thymine in d-ApT and d-TpA profoundly distort the pyrimidine, they do not otherwise significantly alter the conformation of these compounds relative to the unsubstituted dinucleoside monophosphates. The one exception is the thymine glycol of d-T_gpA, which appears to have a higher syn population than the parent compound.