Masurier N, Lafont O, Estour F
Umr 6014, Cnrs, Université de Rouen, INSA de Rouen, Laboratoire de pharmacochimie, Ufr de médecine et de pharmacie, 22, boulevard Gambetta, F 76183 Rouen.
Ann Pharm Fr. 2007 Mar;65(2):126-33.
Among all molecules used to develop biomimetic catalysts, cyclodextrins are extremely attractive compounds. These oligosaccharides can form inclusion complexes with various organic substrates and in particular with organophosphorus poisons, which are widely used as chemical weapons and insecticides. Soman, a frightening neurotoxic agent, once "trapped" in the internal cavity of beta-cyclodextrin can moreover undergo the nucleophilic attack of an oligosaccharide hydroxyl group, miming the first step of the enzymatic process. Selective substitution of beta-cyclodextrin by a 2-iodosobenzoic acid derivative has enabled effective synthesis of scavangers against organophosphorus compounds. Hydrolysis trials were carried out with paraoxon, as an organophosphorus model. The OP-hydrolyzing activity could reach more than two order of magnitude compared with free 2-iodosobenzoïc acid. Nevertheless, hydrolysis of paraoxon showed saturation kinetics. Although the activity was strongly dependent on the relative position of the reactive group, these results showed the interest of a strategy, resulting in the "trapping" of the organophosphorus substrate in the internal cavity of the oligosaccharide in order to maintain it near the catalytic function.
在所有用于开发仿生催化剂的分子中，环糊精是极具吸引力的化合物。这些寡糖能与各种有机底物形成包合物，尤其是与作为化学武器和杀虫剂广泛使用的有机磷毒物。索曼，一种可怕的神经毒剂，一旦“被困”在β-环糊精的内腔中，还能经历寡糖羟基的亲核攻击，模拟酶促过程的第一步。用2-碘苯甲酸衍生物对β-环糊精进行选择性取代，已能有效合成针对有机磷化合物的清除剂。以对氧磷作为有机磷模型进行了水解试验。与游离的2-碘苯甲酸相比，OP水解活性可达到两个以上数量级。然而，对氧磷的水解表现出饱和动力学。尽管活性强烈依赖于反应基团的相对位置，但这些结果表明了一种策略的意义，即通过将有机磷底物“捕获”在寡糖的内腔中，使其保持在催化功能附近。
