Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

Abstract

SummaryThe aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target.

Detoxification of VX and Other V‐Type Nerve Agents in Water at 37 °C and pH 7.4 by Substituted Sulfonatocalix[4]arenes

“…[4] With only af ew exceptions, [5] studies on synthetic scavengers have so far concentrated on cyclodextrin derivatives. [6] Their mode of action is expected to resemble that of proteins,w ith an initial complexation step that positions the phosphorus atom of the nerve agent close to asubstituent on the cyclodextrin ring to facilitate the reaction. Despite notable success in this context, [6] cyclodextrins that detoxify V-type nerve agents have so far remained elusive.A possible explanation could be that V-type nerve agents are poor substrates for cyclodextrins because of their protonated side chain amino groups and, hence,p olar nature at physiological pH values.…”

“…[6] Their mode of action is expected to resemble that of proteins,w ith an initial complexation step that positions the phosphorus atom of the nerve agent close to asubstituent on the cyclodextrin ring to facilitate the reaction. Despite notable success in this context, [6] cyclodextrins that detoxify V-type nerve agents have so far remained elusive.A possible explanation could be that V-type nerve agents are poor substrates for cyclodextrins because of their protonated side chain amino groups and, hence,p olar nature at physiological pH values. [7] If this assumption is correct, hosts for ammonium ions in water should be more promising scaffolds for scavengers for V-type nerve agents.This idea is consistent with established design principles of supramolecular catalysts and reagents.…”

Supramolecular Catalytic System Based on β-Cyclodextrin, Sodium Dodecyl Sulfate and Pralidoxime for the Hydrolysis of Paraoxon

“…It is known that the inclusion of the nitrophenoxyl part in the cyclodextrin cavity implies a sufficient affinity between the phosphorus atom and the secondary hydroxy groups, which promotes hydrolysis. [3] In our case, the macrocycle cavity is occupied by an alkyl chain of SDS, which prevents the binding of POX and causes a slight decrease in the rate constant. This is confirmed by 1 H NMR spectroscopy, where the largest chemical shift is observed for the aromatic proton near the oxime group in the triple system solution with POX ( Figure 7).…”

“…[4] Among supramolecular host macrocycles special attention is given to cyclodextrins that are particularly versatile building blocks for the design of materials for nerve agent sensors [5,6] and decontamination. [3,7] Such popularity is explained by the high affinity of the internal hydrophobic cavity of cyclodextrins to waterinsoluble organophosphorus compounds.…”

“…[1] Within this approach, a key role is given to the design of macrocyclic scaffolds, which have a high selectivity for many organic reactions, in particular, hydrolysis of esters of phosphorus acids [2,3] being one of the ways to detoxify organophosphate neurotoxins and ecotoxicants. [4] Among supramolecular host macrocycles special attention is given to cyclodextrins that are particularly versatile building blocks for the design of materials for nerve agent sensors [5,6] and decontamination.…”