Supramolecular chemistry and chemical warfare agents: from fundamentals of recognition to catalysis and sensing

Abstract

Supramolecular chemistry presents many possible avenues for the mitigation of the effects of chemical warfare agents (CWAs), including sensing, catalysis and sequestration. To-date, efforts in this field both to study fundamental interactions between CWAs and to design and exploit host systems remain sporadic. In this tutorial review the non-covalent recognition of CWAs is considered from first principles, including taking inspiration from enzymatic systems, and gaps in fundamental knowledge are indicated. Examples of synthetic systems developed for the recognition of CWAs are discussed with a focus on the supramolecular complexation behaviour and non-covalent approaches rather than on the proposed applications.

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

“…Moreover,t he extents of the shifts suggest that complex geometries are preferred, with the cationic ammonium group located inside the calixarene cavity.A sac onsequence,t he phosphorus atom of the nerve agent should be preferentially oriented near the hydroxamic acid group of the scavenger, thus facilitating reaction. An NMR titration under the same conditions yielded abinding constant log K a of 4.11 AE 0.12 for the complex between 2c and VX, thus confirming the appreciable affinity of the sulfonatocalix [4]arene for positively charged nerve agents in water.…”

“…

Abstract: Sulfonatocalix [4]arenes with an appended hydroxamic acid residue can detoxify VX and related V-type neurotoxico rganophosphonates with half-lives down to 3min in aqueous buffer at 37 8 8Cand pH 7.4. The detoxification activity is attributed to the millimolar affinity of the calixarene moiety for the positively charged organophosphonates in combination with the correct arrangement of the hydroxamic acid group.

…”

“…[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.…”

“…Our approach involved the use of sulfonatocalix [4]arenes that are also strong cation binders in water. [10,11] These calixarenes were decorated with asubstituent containing ahydroxamic acid, which is known to detoxify OPs.…”

Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro

“…However, the main disadvantage of protein-based scavengers is the low physiological tolerance in vivo. In contrast, substituted cyclodextrins (CDs) represent supramolecular scavengers with low inherent toxicity in vivo and the capacity of forming different kinds of complexes (Naguib, 2007;Sambrook and Notman, 2013).…”