Alkylating potential of styrene oxide: reactions and factors involved in the alkylation process Articles uri icon

authors

  • González Pérez, Marina
  • Gómez Bombarelli, Rafael
  • PEREZ PRIOR, MARIA TERESA
  • AERNAS VALGAÑON, JORGE
  • GARCIA SANTOS, MARIA PILAR
  • Calle, Emilio
  • Casado, Julio

publication date

  • September 2014

start page

  • 1853

end page

  • 1859

issue

  • 10

volume

  • 27

International Standard Serial Number (ISSN)

  • 0893-228X

abstract

  • The chemical reactivity of styrene-7,8-oxide (SO), an alkylating agent with high affinity for the guanine-N7 position and a probable carcinogen for humans, with 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, was investigated kinetically in water/dioxane media. UV-vis spectrophotometry and ultrafast liquid chromatography were used to monitor the reactions involved. It was found that in the alkylation process four reactions occur simultaneously: (a) the formation of a beta-NBP-SO adduct through an SN2 mechanism; (b) the acid-catalyzed formation of the stable alfa-NBP-SO adduct through an SN2′ mechanism; (c) the base-catalyzed hydrolysis of the beta-adduct, and (d) the acid-catalyzed hydrolysis of SO. At 37.5°C and pH = 7.0 (in 7:3 water/dioxane medium), the values of the respective reaction rate constants were as follows: kalkbeta = (2.1 ± 0.3) × 10-4 M-1 s-1, kalkalfa = (1.0 ± 0.1) × 10-4 M-1 s-1, khyd AD = (3.06 ± 0.09) × 10-6 s-1, and khyd = (4.2 ± 0.9) × 10-6 s-1. These values show that, in order to determine the alkylating potential of SO, none of the four reactions involved can be neglected. Temperature and pH were found to exert a strong in fluence on the values of some parameters that may be useful to investigate possible chemicobiological correlations (e.g., in the pH 5.81-7.69 range, the fraction of total adducts formed increased from 24% to 90% of the initial SO, whereas the adduct lifetime of the unstable beta-adduct, which gives an idea of the permanence of the adduct over time, decreased from 32358 to 13313 min). A consequence of these results is that the conclusions drawn in studies addressing alkylation reactions at temperatures and/or pH far from those of biological conditions should be considered with some reserve. (Chemical Equation Presented).

keywords

  • alcohols; adducts; kinetic parameters; hydrolysis; post-translational modification