Theoretical Studies of DNA Base Deamination. 2. Ab Initio Study of DNA Base Diazonium Ions and of their Linear, Unimolecular Dediazoniation Paths


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 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.



Keywords and Phrases

adenine derivative; cytosine derivative; diazonium compound; guanine derivative; chemical reaction; chemical structure; deamination; DNA cross linking; DNA modification; molecular model; molecular stability; reaction analysis; structure analysis

International Standard Serial Number (ISSN)

0002-7863; 1520-5126

Document Type

Article - Journal

Document Version


File Type





© 1999 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Jun 1999