Detection of Chemical Warfare Agents via Supramolecular Multitopic Approach for the Development of High Performance Sensing Devices.

Organophosphorous (OP) compounds are the most toxic known chemicals, used as weapons of mass destruction called Nerve Agents (NAs). Their high toxicity for humans is due to the strong inhibition of Acetycholinesterase enzyme in human synapses, hindering the hydrolysis of acetylcholine neurotransmitter, thus leading to cholinergic crisis. Despite the Organization for Prohibition of Chemical Weapons (OPCW) banned the production, use and stockpiling of OP nerve agents, these compounds still represent a threat for human health and environment protection. For this reason, detection and monitoring systems are desirable. Due to their high toxicity, direct use of NA for research purpose is not feasible. Model compounds with similar structure and properties but reduced toxicity, called simulants, are commonly used in research field. Current instrumental detection systems such as mass spectrometry and gas chromatography are really sensitive, but require unwieldy expensive equipment, affording slow, non-selective response. Molecular probes are preferred and represent a successful tool for the realization of cost-effective, easy to use detection and monitoring systems. Molecular detection of Nerve Agents today involves two main approaches classified on the basis of the interactions involved: i) covalent method and ii) supramolecular approach. Covalent-based molecular probes provide a covalent irreversible reaction with the phosphate atom of NA, leading to non-reusable low-selective sensors. By the contrast, less explored supramolecular detection of nerve agents provides non-covalent reversible interaction (hydrogen bond, metal coordination, hydrophobic effect)between the receptor (host) and the selected analyte (guest). In addition the emerging multi-topic approach enable to involve several interaction sites in the host, complementary to the interaction sites of the selected guest, leading to reusable sensors with high selectivity, avoiding the possibility of false positive response. With the aim to obtain highly selective detection of Nerve Agents simulants, several fluorescent supramolecular receptors were carefully designed with a bio-inspired approach, mimicking the multi-topic recognition mode of the natural enzymes. Geometry of selected guest was analysed focusing on functional groups available for supramolecular interactions, evaluating their distances and position, in order to realise a complementary host, able to selectively interact with the guest and give a fast detectable response. To this aim, fluorophore scaffolds were properly functionalised, obtaining unprecedented selectivity and sensitivity towards OP compounds. The geometry of host-guest (H-G) complexes were investigated to better understand the poorly explored supramolecular features of Nerve Agents simulants. Finally, practical test strips were performed, in order to prove the potential application of this receptor for detection and monitoring devices for Nerve Agents in gas phase.