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

  title={Chemical carcinogens in non-enzymatic cytosine deamination: 3-isocyanatoacrylonitrile},
  author={Rainer Glaser and Hong Wu and Francisca von Saint Paul},
  journal={Journal of Molecular Modeling},
  pages={731 - 737}
AbstractUracil 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… 
4 Citations
Asymmetry in the N-inversion of heteroarene imines: pyrimidin-4(3H)-imine, pyridin-2(1H)-imine, and 1H-purine-6(9H)-imine.
The detailed study of structures and electronic structures along the entire N-inversion path of the isomerization PMI revealed a remarkable stabilization due to asymmetry in the ascent region from the (E)-isomer to ITS, and this amidine effect predicts lower N- inversion barriers in analogous imines with (Z)-preference energies.
On the Route to the Photogeneration of Heteroaryl Cations. The Case of Halothiophenes.
Specific trapping by using oxygen along with computational analysis carried out by means of a density functional method support that, in the case of iodo derivatives, homolytic thienyl-I bond fragmentation occurs first and heteroaryl cations are formed by electron transfer within the triplet radical pair, thus opening an indirect access to such cations.
Nitrosative cytosine deamination. An exploration of the chemistry emanating from deamination with pyrimidine ring-opening.
The experimental results provide a rationale as to why (Z)-3-aminoacrylonitrile 10 as the most likely deamination product of cytosine aside from uracil would have escaped detection in in vitro studies: they would have oligomerized.


Cytosine catalysis of nitrosative guanine deamination and interstrand cross-link formation.
It is argued that this environment-induced switch causes entirely different reaction paths to products as compared to the respective "free nucleobase" chemistry, and the complete consistency is demonstrated of this mechanistic model with all known experimental results.
5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazole and 5-cyanoamino-4-imidazolecarboxylic acid intermediates in nitrosative guanosine deamination: evidence from 18O-labeling experiments.
The results show that oxanosine is formed via 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole, 5, and its 1,4-addition product 6, which leads to aromatization and greatly dominates over water addition to the cyanoiminos group of 5 to form 5-guanidinyliden- 4-oxometrichylene, 7.
Nitrosative adenine deamination: facile pyrimidine ring-opening in the dediazoniation of adeninediazonium ion.
The results suggest that 4-cyano-5-isocyano-imidazole, 4, and 4,5-dicyanoimidrazole, 5, might be formed to some extent in nitrosative deaminations of adenine.
Demonstration of an alternative mechanism for G-to-G cross-link formation.
All known products of nitrosative guanine deamination are consistent with the postulate of pyrimidine ring-opening, and the results suggest that both cross-links are of comparable thermodynamic stability, and that there are no a priori energetic or structural reasons that would prevent the formation of the structure isomer in the model reaction or in DNA.
Isolation and characterization of diazoate intermediate upon nitrous acid and nitric oxide treatment of 2'-deoxycytidine.
The results show that the diazoate is generated as a stable intermediate in the reactions of dCyd with HNO2 and NO and that the major product is the dIAzoate but not dUrd in the initial stage of the reactions.
Synergism of catalysis and reaction center rehybridization in nucleophilic additions to cumulenes: the one-, two-, three-water hydrolyses of carbodiimide and methyleneimine.
The results of a theoretical study of the one-, two- and three-water hydrolyses of carbodiimide and the one- and two- water hydrolysis of methyleneimine are presented and the placement of the third water molecule in the proton transfer chain is considered to be of little catalytic relevance.
Review of the occupational exposure to isocyanates: Mechanisms of action
The overall conclusion is that because humans are not exposed to high levels of respiratory isocyanate particles, concerns over the possible development of lung tumors should not be relevant.
Synergism of Catalysis and Reaction Center Rehybridization. An ab Initio Study of the Hydrolysis of the Parent Carbodiimide
to include compounds with important roles in a wide array of chemical applications. 3 The most important reactions of carbodiimides all involve nucleophilic attack, and the nucleophilic addition of
Investigation of the competitive rate of derivatization of several secondary amines with phenylisocyanate (PHI), hexamethylene-1,6-diisocyanate (HDI), 4,4'-methylenebis(phenyl isocyanate) (MDI) and toluene diisocyanate (TDI) in liquid medium.
The results show that the order of reactivity, which doesn't change with the isocyanate as well as with the solvent used, is the following: DBA > MAP > MOPIP > MAMA, and Hindered aromatic diisocyanates show a greater difference in reactivity with the derivatization agents.
A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine.
It is shown that a bacterial cytosine methyltransferase can convert 5-methylcytosine in DNA to thymine and that this reaction creates a mutational hot spot at a site of DNA methylation, which is expected to contribute to mutations at CG dinucleotides in precancerous cells.