The reactivity of vinyl compounds as alkylating agents

Abstract

The reactions of 4-(p-nitrobenzyl)pyridine (a trap for alkylating agents with nucleophilicity similar to that of DNA) with the vinyl compounds acrylonitrile, acrylamide, acrylic acid, and acrolein, which can act as alkylating agents of DNA, were investigated. The following conclusions were drawn: (1) vinyl compounds show an alkylating capacity on 4-(p-nitrobenzyl)pyridine. The sequence of the alkylating potential was found to be acrylonitrile [ acrylamide [ acrylic acid [ acrolein (alkylation with acrolein was not observed after 3 weeks). The formation of adducts with acrylonitrile was approximately 10-and 100-fold faster than with acrylamide and acrylic acid, respectively, which is consistent with its highly carcinogenic and mutagenic activity. (2) 4-(p-Nitrobenzyl)pyridine alkylation reactions by vinyl compounds occur through an enthalpycontrolled Michael addition mechanism. The values for the free energy of activation for these reactions with 4-(p-nitrobenzyl)pyridine were: D à G°(37°C) acrylonitrile, 98 ± 1 kJ mol -1 ; acrylamide, 105 ± 2 kJ mol -1 ; acrylic acid, 109 ± 1 kJ mol -1 . (3) Application of Hammett treatment to the kinetic results revealed that these alkylation reactions occur through nucleophilic attack, being moderately accelerated by electron-withdrawing groups.

Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

“…However, the correlation found between the antileishmanial activity and Hammet's electronic constant (σ R ) can help us to get some insights about the mechanism of action of these compounds. The positive coefficient of σ R means a direct correlation between the dependent and independent variables, corroborating previous observations that structurally-related compounds bearing electron-withdrawing groups present greater activity than those with electron donating groups (Céspedes-Camacho et al, 2012;Neau et al, 1982). Although compound 4 (R = SO 2 NH 2 ) presents a substituent with high positive value of σ R , it does not follow this tendency, behaving like an outlier.…”

Mechanistic Models for LAH Reductions of Acetonitrile and Malononitrile. Aggregation Effects of Li+ and AlH3 on Imide–Enamide Equilibria

“…The major obstacle to the second hydride reduction again concerns the imide-enamide equilibrium and the lack of nitrile activity in the enamide ( Z , Z )- 8 . Acrylonitriles are substrates for Michael additions − and the negative charge of the azallyl system further reduces the nitrile’s electrophilicity.…”

Redox-Driven Disassembly of Polymer–Chlorambucil Polyprodrug: Delivery of Anticancer Nitrogen Mustard and DNA Alkylation

“…The alkylating activity of CBL-anchored BCP3 micelles has been investigated with NBP, an in vitro model for alkylation activity. The compound NBP, which shares structural and reactivity feature with guanine, one of the nucleobases in DNA, can serve as a DNA model. , According to Swain–Scott nucleophilicity relationship, the nucleophilicity constants of NBP and N7-position of guanine are nearly the same (3.5–3.6) . These facets allow NBP to act as a proxy for the biological macromolecule DNA.…”