Interaction of 2′-Deoxyadenosine with cis-2-Butene-1,4-dial: Computational Approach to Analysis of Multistep Chemical Reactions

The computational analysis of multistep chemical interactions between 2'-deoxyadenosine and cis-2-butene-1,4-dial has been performed. The applied protocol includes generation of a multistep Gibbs free-energy reaction profile (PCM/M05-2X/6-311+G(d) level) for the transformations of the reagents to products, followed by evaluation of the rate constants, construction of the corresponding kinetic equations, and solving them. Such a procedure allows one to significantly extend the number of experimentally determined steps by addition of the ones computationally predicted. The primary products of the reaction are found to be four diastereomeric adducts characterized by virtually the same stability. The acid-catalyzed dehydration of these adducts leads to a more stable secondary product. Computational verification of UV and NMR spectra has also been performed. It has been revealed that simulated UV and NMR spectra of primary and secondary 2'-deoxyadenosine adducts of cis-2-butene-1,4-dial are in agreement with the experimental observations.