Chemical carcinogens in non-enzymatic cytosine deamination: 3-isocyanatoacrylonitrile.

ABSTRACT: 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-isocyanatoacrylonitrile

SUBMITTER: Glaser R 

PROVIDER: S-EPMC2441498 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature