In silico kinetics and mechanism of interaction of cis-2-butene-1,4-dial with 2'-deoxycytidine

Chem Res Toxicol. 2014 Jun 16;27(6):981-9. doi: 10.1021/tx5000427. Epub 2014 Jun 2.

Abstract

Newly proposed approach involving computational analysis of multistep chemical reactions has been successfully applied to study the interaction between 2'-deoxycytidine and cis-2-butene-1,4-dial, a metabolite of furan. The new method comprises a combination of few steps. They include the prediction of the reaction mechanism, calculation of Gibbs free energies for the reaction pathway, and conversion of barrier energies to rate constants. On the basis of the results of previous steps, corresponding kinetic equations are constructed and solved. Such a procedure allows one to indicate the definite concentration of reaction species (reactants, intermediates, and products) at any moment in time. Obtained results show that 2'-deoxycytidine reacts with cis-2-butene-1,4-dial to form primary products, which are represented by four polycyclic diastereomers. These primary products further transform to more stable secondary product by dehydration, which is catalyzed by acid. The obtained data demonstrate that cis-2-butene-1,4-dial plays a key role in furan-induced carcinogenesis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / chemistry*
  • Deoxycytidine / chemistry*
  • Kinetics
  • Molecular Structure
  • Quantum Theory
  • Stereoisomerism

Substances

  • Aldehydes
  • Deoxycytidine
  • malealdehyde