Mechanistic aspects of the formation of guanidinohydantoin from spiroiminodihydantoin under acidic conditions.
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.
Ye
Yu
Y
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.
Munk
Barbara H
BH
Muller
James G
JG
Cogbill
Alexander
A
Burrows
Cynthia J
CJ
Schlegel
H Bernhard
HB
D006146:Guanidines / Q000138:chemical synthesis*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006827:Hydantoins / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000737:chemistry*
D006146:Guanidines; D006827:Hydantoins; D013141:Spiro Compounds; C467338:guanidinohydantoin; C408822:spiroiminodihydantoin; D006151:Guanosine