Interaction of 2'-deoxyguanosine with cis-2-butene-1,4-dial: Computational approach to analysis of multistep chemical reactions

Abstract

cis-2-Butene-1,4-dial represents a microsomal metabolite of furan, an industrially important chemical found in cigarette smoke, air pollution, and also in canned or jarred food. It is expected to be a human carcinogen. Aim. Investigation of an effect of cis-2-butene-1,4-dial on the 2'-deoxyguanosine which is a model of DNA site. Methods. Optimization of reaction species molecular structures, spectral parameters and Gibbs free energy calculations were performed using Gaussian09 program. Systems of differential equations for kinetics generation were solved using Mathcad15 program. Results. The predicted mechanism of the reaction of cis-2-butene-1,4dial with 2'-deoxyguanosine consists of four-step process formation of four diastereomeric primary adducts and further base-mediated five-step transformation of the primary adducts to the secondary one. The reaction kinetics, which allows defining the concentration change of any reaction species was calculated. Conclusions. Under physiological conditions the interaction between cis-2-butene-1,4-dial and 2'-deoxyguanosine leads to the formation of a stable adduct which could be responsible for the furan genotoxicity.

Risks for public health related to the presence of furan and methylfurans in food

“…Sviatenko et al (2012) applied quantum chemical computer assisted analysis to study the chemical interaction between BDA and dA. A similar technique was applied to study the interactions between BDA and dG (Sviatenko et al, 2014). For the reactions of BDA with dA and dG, the authors calculated that the primary reaction products would consist of four diastereoisomeric adducts for each nucleoside (for an example of these structure see Figure 7).…”

In Silico Alkaline Hydrolysis of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine: Density Functional Theory Investigation

“…In spite of limited data on kinetics of HMX alkaline hydrolysis being evaluable, − there is no convincing answer why the initial denitration step is so slow. To shed a light on the mentioned issues, we applied a semiempirical method recently developed by us − for the analysis of multistep chemical reactions, which allows us to computationally generate the amount and nature of all intermediate steps that take place between decomposition of reagents and formation of products, including the speed-limited steps. The method allows us to obtain the kinetic equations for a total process and all contributing chemical steps, to predict speeds of decay of reagents and products accumulating under conditions studied (or not yet studied) experimentally, such as change of concentration, pH, temperature, etc.…”