10.1021/ja9841254.s001
Rainer Glaser
Rainer
Glaser
Sundeep Rayat
Sundeep
Rayat
Michael Lewis
Michael
Lewis
Man-Shick Son
Man-Shick
Son
Sarah Meyer
Sarah
Meyer
Theoretical Studies of DNA Base Deamination. 2. Ab Initio Study of
DNA Base Diazonium Ions and of Their Linear, Unimolecular
Dediazoniation Paths<sup>†</sup><sup>,</sup><sup>§</sup>
American Chemical Society
1999
dediazoniation paths
transition state structure
DNA bases cytosine
DNA base diazonium ions
2. Ab Initio Study
DNA base acts
nucleophilic substitution
c structure
DNA base
Theoretical Studies
DNA Base Diazonium Ions
diazonium ions
product analyses
iminol tautomers
kcal
guaninediazonium ion 5
unimolecular dediazoniations
pyrimidine ring opening
diazonium ions 1
guaninediazonium ion
6 b
iminol tautomer HO
cation 6
cations 2
diazonium ion structure
DNA bases
unimolecular dissociation
unimolecular dediazoniation paths
ab initio study
DNA Base Deamination
1999-06-16 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Theoretical_Studies_of_DNA_Base_Deamination_2_Ab_Initio_Study_of_DNA_Base_Diazonium_Ions_and_of_Their_Linear_Unimolecular_Dediazoniation_Paths_sup_sup_sup_sup_sup_sup_/3673578
Deamination 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 <b>1</b>, <b>3</b>, and
<b>5</b>, derived by diazotization of the DNA bases cytosine, adenine, and guanine, respectively, and of their
unimolecular dediazoniations to form the cations <b>2</b>, <b>4</b>, and <b>6</b>, respectively. The dediazoniation paths of two
iminol tautomers of <b>1</b> and <b>5</b> 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 (<b>a</b> structure)
as well as for an electrostatically bound cation−dinitrogen complex (<b>b</b> structure), and these minima are separated
by a transition state structure (<b>c</b> 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 <b>HO-5</b>
of the guaninediazonium ion was found to be more stable than the guaninediazonium ion <b>5</b>. Moreover, it was
found that the unimolecular dissociation of <b>5</b> is accompanied by a concomitant pyrimidine ring opening leading
to <b>6b</b> rather than the generally discussed cation <b>6a</b>. 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−N<sub>2</sub><sup>+</sup> (3.7 kcal/mol) < A−N<sub>2</sub><sup>+</sup> (9.0 kcal/mol)
≈ G−N<sub>2</sub><sup>+</sup> (<10 kcal/mol) ≪ Ph−N<sub>2</sub><sup>+</sup> (26.6 kcal/mol), and mechanistic implications are discussed.