Reactivity Pattern of Bromonucleosides Induced by 2-Hydroxypropyl Radicals: Photochemical, Radiation Chemical, and Computational Studies

Abstract

The bromonucleosides (BrdX's) 5-bromo-2'-deoxyuridine (BrdU), 5-bromo-2'-deoxycytidine (BrdC), 8-bromo-2'-deoxyadenosine (BrdA), and 5-bromo-2'-deoxyguanosine (BrdG) may substitute for ordinary nucleosides in DNA. As indicated by electron-stimulated desorption experiments, such a modified biopolymer is greater than 2-3-fold more sensitive to damage induced by excess electrons. The other major product of water radiolysis, the (•)OH radical, may form a number of other radicals in chemical reactions with the complex content of the cell. Thus, the well-proved BrdU-labeled DNA radiosensitivity may be, at least in part, related to secondary organic radicals. Therefore, in the current study, the propensity of BrdX's to damage induced by 2-hydroxypropyl radical (OHisop(•))-a prototype radical species-was investigated. The HPLC and LC-MS analyses revealed the formation of two major products from the brominated pyrimidine nucleosides, a native nucleoside and an adduct of BrdX and OHisop(•) , and only an adduct of BrdX from the bromopurine nucleosides. Quantum chemical calculations ascribed this evident difference between purines and pyrimidines to the electron transfer from OHisop(•) to BrdX that is especially favorable in pyrimidines.

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

“…This is why the reactivity of halogenated 2 0 -deoxynucleosides (brominated (BrdX) or iodinated (IdX)) toward organic radicals and solvated electrons (both types of species are produced during the radiolysis of cellular environment) was investigated in the current project. Using HPLC and LC-MS techniques, it was demonstrated that beside the substitution of bromine atom by 2-hydroxypropyl radical (OHisop ), electron transfer from OHisop to BrdX takes place only for 5-bromo-2 0 -deoxyuridine (BrdU) and 5-bromo-2 0 -deoxycytydine (BrdC) due to larger electron affinity (EA) of pyrimidines than purines [76]. The larger EA of brominated pyrimidines also accounts for more efficient damage induced by hydrated electrons in the trimeric oligonucleotides, TBrdXT, labeled with BrdU or BrdC [77].…”