32645-65-1

Abstract Ultrasound is extensively used in medical field for a number of applications including targeted killing of cancer cells. DNA is one of the most susceptible entities in any kind of free radical induced reactions in living systems. In the present work, the transformation of thymidine (dT) induced by ultrasound (US) was investigated using high resolution mass spectrometry (LC-Q-ToF-MS). dT was subjected to sonolysis under four different frequencies (200, 350, 620 and 1000 kHz) and at three power densities (10.5, 24.5 and 42 W/mL) in aerated as well as argon saturated conditions. A total of twenty modified nucleosides including non-fully characterized dT dimeric compounds were detected by LC-Q-ToF-MS. Out of these products, seven were obtained only in the argon atmosphere and two only in the aerated conditions. Among the identified products, there were base modified products and sugar modified products. The products were formed by the reaction of hydroxyl radical and hydrogen atom. Under aerated conditions, the reactions proceed via the formation of hydroperoxides, while in argon atmosphere disproportionation and radical recombinations predominate. The study provides a complete picture of sonochemical transformation pathways of dT which has relevance in DNA damage under ultrasound exposure.

The main reactions of 6-hydroxy-5,6-dihydrothymid-5-yl radicals, specifically obtained by electron capture dissociation of the trans diastereomers of 5-bromo-6-hydroxy-5,6-dihydrothymidine, were determined in aqueous solutions on the basis of final product analysis.In oxygen-free aqueous solutions a complex mixture of both monomeric and dimeric decomposition products was produced.It is worth mentioning the radiation-induced formation of modified nucleosides which involves the transient generation of 5-(2'-deoxyuridyl)methyl radical.This may be explained in terms of initial formation of 6-hydroxy-5,6-dihydrothymid-5-yl radicals, followed by dehydration and subsequent deprotonation.

Oxidation of thymidine by KHSO5 gave thymidine glycols, while a similar treatment with Na2S2O8 gave 5-hydroxymethyl-2'-deoxyuridine.