Trapping acrylamide by a Michael addition: A computational study of the reaction between acrylamide and niacin

Abstract

Neurotoxic and carcinogenic acrylamide (ACR) is present in many food products. This finding spurred numerous studies for ACR scavengers. Niacin is putatively one of them because it reacts via Michael addition with ACR to form 1‐propanamide‐3‐carboxy pyridinium. Here, we study the mechanism and energetics of this reaction in aqueous solution by density functional theory. The CAM‐B3LYP and M06‐2X functionals with the 6‐31+G(d,p) basis set and implicit solvent were used. Single point calculations at the MP2 level with the same basis set were performed on optimized structures obtained at the M06‐2X level. Solvent effects comprehended both polarizable continuum model and solvation model density solvation models. The calculated NMR chemical shifts of 1‐propanamide‐3‐carboxy pyridinium are in agreement with experimental results. The theoretical study favors thermodynamically the formation of the adduct while the calculated activation energies turn out not to be too dissimilar from the ones measured for the alkylation reaction between ACR and 4(p‐nitrobenzyl)pyridine. © 2014 Wiley Periodicals, Inc.

Molecular determinants of acrylamide neurotoxicity through covalent docking

“…We first searched in the literature for human proteins targeted by acrylamide that have been associated to neurotoxic effects (Ferreira de Lima and Carloni, 2011;Papamokos et al, 2014) or used to biomonitor ACR exposure (Barber et al, 2001;Basile et al, 2008). In addition, we also included proteins listed as acrylamide targets in several chemical and toxicology databases, namely ChEMBL (Davies et al, 2015;Mendez et al, 2018) and T3DB (Lim et al, 2009;Wishart et al, 2015), respectively.…”

“…Hence, here we have assessed whether covalent docking could be used as a computational tool to characterize ACR reactivity and its (neuro) toxic effects at the molecular level. In particular, as a follow-up of previous computational works by some of us (Ferreira de Lima and Carloni, 2011;Papamokos et al, 2014), we compiled a list of acrylamide protein targets and performed a systematic molecular study using covalent docking. We focused on neuronal protein targets associated with neurotoxic symptoms of acrylamide, as well as acrylamide-modified proteins detectable in plasma and liver that can be used as biomarkers to monitor ACR exposure.…”