Departamento de Química Fisica, Universidad de Salamanca, E-37008 Salamanca, Spain.
J Org Chem. 2010 Mar 5;75(5):1444-9. doi: 10.1021/jo902329q.
The formation of chemical species with DNA-damaging and mutagenic activity for bacterial test systems was detected in sorbic acid-nitrite mixtures. 1,4-Dinitro-2-methylpyrrole (NMP), one the main products resulting from the reaction between sorbic acid and nitrite, has mutagenic properties, and here its alkylating capacity was investigated. The conclusions drawn are as follows: (i) In aqueous medium, after the addition of a hydroxide ion and the subsequent loss of nitrite, NMP affords 5-methyl-3-nitro-1H-pyrrol-2-ol. This species is in equilibrium with 5-methyl-3-nitro-1H-pyrrol-2(5H)-one, the effective alkylating agent responsible for the genotoxic capacity of NMP; (ii) 5-methyl-3-nitro-1H-pyrrol-2(5H)-one alkylates 4-(p-nitrobenzyl)pyridine (NBP), a molecule with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; epsilon = 1.14 x 10(4) M(-1) cm(-1)); (iii) The calculated energy barrier for the alkylation of NBP for NMP and the value of the fraction of alkylating agent forming the adduct are consistent with the observed mutagenicity of NMP; (iv) The reactivity of NMP can be explained in terms of the instability of the N-NO(2) bond as well as the effect of this group on aromaticity.
山梨酸-亚硝酸盐混合物中检测到具有 DNA 损伤和致突变活性的化学物质的形成。1,4-二硝基-2-甲基吡咯（NMP）是山梨酸和亚硝酸盐反应的主要产物之一，具有致突变特性，本文研究了其烷化能力。得出的结论如下：（i）在水介质中，加入氢氧根离子并随后失去亚硝酸盐后，NMP 生成 5-甲基-3-硝基-1H-吡咯-2-醇。该物质与 5-甲基-3-硝基-1H-吡咯-2(5H)-酮处于平衡状态，后者是负责 NMP 遗传毒性的有效烷化剂；（ii）5-甲基-3-硝基-1H-吡咯-2(5H)-酮烷化 4-（对硝基苄基）吡啶（NBP），后者具有与 DNA 碱基相似的亲核特性，形成加合物（AD；epsilon = 1.14 x 10(4) M(-1) cm(-1)）；（iii）NMP 对 NBP 的烷化的计算能垒和形成加合物的烷化剂分数的值与 NMP 的观察到的致突变性一致；（iv）NMP 的反应性可以用 N-NO(2)键的不稳定性以及该基团对芳构性的影响来解释。
