Mechanistic aspects of the formation of guanidinohydantoin from spiroiminodihydantoin under acidic conditions.
نویسندگان
چکیده
Experimentally, it was observed that the oxidized guanine lesion spiroiminodihydantoin (Sp) contained in highly purified oligodeoxynucleotides slowly converts to guanidinohydantoin (Gh). The reaction is accelerated in the presence of acid. The possible mechanisms of this transformation have been analyzed computationally. Specifically, the potential energy surface for formation of Gh from Sp has been mapped using B3LYP density functional theory, the aug-cc-pVTZ and 6-31+G(d,p) basis sets, and the integral equation formalism for the polarizable continuum model (IEF-PCM) solvation model. The results favor a mechanism in which proton-assisted hydration of the C6 carbonyl group forming a gem-diol leads to ring opening of the iminohydantoin ring. The resulting species resembles a beta-ketoacid in its ability to decarboxylate; tautomerization of the resulting enol forms Gh. The results of these studies indicate that incubation of nucleosides or oligonucleotides containing Sp should be avoided in acidic media when high purity or an accurate assessment of the amounts of hydantoin lesions is desired.
منابع مشابه
Calculation of pKa values of nucleobases and the guanine oxidation products guanidinohydantoin and spiroiminodihydantoin using density functional theory and a polarizable continuum model.
An efficient computational method has been identified that uses B3LYP density functional theory, IEF-PCM solvation modeling with a modified UFF cavity, and Boltzmann weighting of tautomers to predict the site-specific and global pKa of DNA nucleobases and their oxidation products. The method has been used to evaluate the acidity of guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), two hig...
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عنوان ژورنال:
- Chemical research in toxicology
دوره 22 3 شماره
صفحات -
تاریخ انتشار 2009