Chemical Carcinogens in Non-Enzymatic Cytosine Deamination: 3-Isocyanatoacrylonitrile


Uracil has long been known as the main product of nitrosative cytosine deamination in aqueous solution. Recent mechanistic studies of cytosinediazonium ion suggest that the cation formed by its dediazoniation can ring-open to N-protonated (Z,s-cis)-3-isocyanatoacrylonitrile 7. Stereochemical preferences are discussed of the 3-isocyanatoacrylonitriles (Z,s-cis)-10, (E,s-cis)-11, (Z, s-trans)-12, and (E,s-trans)-13. The electronic structures of 7 and 10-13 have been analyzed and a rationale is provided for the thermodynamic preference for (Z,s-cis)-10. It is shown that s-cis/s-trans-interconversion occurs via C-N rotation-inversion paths with barriers below 3 kcal mol-1. The proton affinities of 3-isocyanatoacrylonitrile 10 and water are nearly identical and, thus, 3-isocyanatoacrylonitriles can and should be formed in aqueous media from 7 along with 3-aminoacrylonitriles 9. The results highlight the relevance of the chemistry of 3-isocyanatoacrylonitriles for the understanding of the chemical toxicology of nitrosation of the nucleobase cytosine.



Keywords and Phrases

3 Aminoacrylonitrile Derivative; 3 Isocyanatoacrylonitrile Derivative; Carbon; Cytosine; Nitrogen; Nucleic Acid Base; Proton; Toxic Substance; Unclassified Drug; Water; Aqueous Solution; Binding Affinity; Chemical Structure; Cis Trans Isomerism; Controlled Study; Deamination; Nitrosation; Rotation; Stereochemistry; Structure Analysis; Thermodynamics; Acrylonitrile; Carcinogens; Cytidine; Imaging; Three-Dimensional; Isocyanates; Models; Molecular; Molecular Conformation; Protons; Thermodynamics; Ab Initio; Carcinogenesis; Chemical Toxicology; Electronic Structure; Inversion; Non-Covalent Bonding; Rotational Barrier

International Standard Serial Number (ISSN)

1610-2940; 0948-5023

Document Type

Article - Journal

Document Version


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© 2006 Springer Verlag, All rights reserved.

Publication Date

01 Jul 2006

PubMed ID