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Theoretical Studies of DNA Base Deamination. 2. Ab Initio Study of DNA Base Diazonium Ions and of Their Linear, Unimolecular Dediazoniation Paths†,§
journal contribution
posted on 1999-06-16, 00:00 authored by Rainer Glaser, Sundeep Rayat, Michael Lewis, Man-Shick Son, Sarah MeyerDeamination of the DNA bases cytosine, adenine, and guanine can be achieved by way of diazotization
and the diazonium ions of the DNA bases are considered to be the key intermediates. The DNA base diazonium
ions are thought to undergo nucleophilic substitution by water or other available nucleophiles. Cross-link
formation is thought to occur if the amino group of a neighboring DNA base acts as the nucleophile. All
mechanistic hypotheses invoking DNA base diazonium ions are based on product analyses and deduction and
analogy to the chemistry of aromatic primary amines while none of the DNA base diazonium ions has been
observed or characterized directly. We report the results of an ab initio study of the diazonium ions 1, 3, and
5, derived by diazotization of the DNA bases cytosine, adenine, and guanine, respectively, and of their
unimolecular dediazoniations to form the cations 2, 4, and 6, respectively. The dediazoniation paths of two
iminol tautomers of 1 and 5 also were considered. The unimolecular dediazoniation paths were explored and
none of these corresponds to a simple Morse-type single-minimum potential. Instead, double-minimum potential
curves are found in most cases, that is, minima exist both for a classical diazonium ion structure (a structure)
as well as for an electrostatically bound cation−dinitrogen complex (b structure), and these minima are separated
by a transition state structure (c structure). Depending on the DNA base, either minimum may be preferred
and each minimum may or may not be bound with respect to the free fragments. The iminol tautomer HO-5
of the guaninediazonium ion was found to be more stable than the guaninediazonium ion 5. Moreover, it was
found that the unimolecular dissociation of 5 is accompanied by a concomitant pyrimidine ring opening leading
to 6b rather than the generally discussed cation 6a. This discovery leads to the proposition of a mechanism
that is capable of accounting for all available experimental and theoretical data. The stabilities of the DNA
base diazonium ions toward dediazoniation follow the order C−N2+ (3.7 kcal/mol) < A−N2+ (9.0 kcal/mol)
≈ G−N2+ (<10 kcal/mol) ≪ Ph−N2+ (26.6 kcal/mol), and mechanistic implications are discussed.
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dediazoniation pathstransition state structureDNA bases cytosineDNA base diazonium ions2. Ab Initio StudyDNA base actsnucleophilic substitutionc structureDNA baseTheoretical StudiesDNA Base Diazonium Ionsdiazonium ionsproduct analysesiminol tautomerskcalguaninediazonium ion 5unimolecular dediazoniationspyrimidine ring openingdiazonium ions 1guaninediazonium ion6 biminol tautomer HOcation 6cations 2diazonium ion structureDNA basesunimolecular dissociationunimolecular dediazoniation pathsab initio studyDNA Base Deamination
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