6533b7ddfe1ef96bd1273e69

RESEARCH PRODUCT

Chromogenic detection of nerve agent mimics

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The current rise in international concern over criminal terrorist attacks via chemical warfare (CW) agents has resulted in an increasing interest in the detection of these lethal chemicals. Among CW species, nerve agents are extremely dangerous and their high toxicity and ease of production underscore the need to detect these deadly chemicals via quick and reliable procedures. A number of detection systems have been developed, most of them based on enzymatic and physical methodologies. However, these usually show limitations such as low selectivity, lack of portability and a certain complexity in their use. An alternative to these classical methods that has been gaining interest in recent years is the development of fluorogenic or chromogenic chemosensors or reagents. Reported paradigms involve PET-based fluorescent probes, colorimetric probes with oximate-containing derivatives, molecular imprinting polymers, nanoparticles, carbon nanotubes, porous silicon or displacement-like assays. Most of these reported protocols rely on fluorescence changes and as far as we know chromogenic systems for nerve agent detection in aqueous solution or as vapour are rare. Some reported colorimetric examples employ enzymatic methods and are based on the inhibition of the activity of the enzyme acetylcholine esterase. Despite these interesting examples, colorimetric detection is particularly appealing as it requires low-cost and widely used instrumentation and offers the possibility to detect ‘‘with the naked eye’’ target analytes in rapid semi-quantitative assays. Following our interest in using supramolecular-inspired concepts for the development of chromogenic protocols, we report herein the design of colorimetric probes for nerve agents. Traditionally the development of colorimetric probes usually relies on the advanced design of two components: (i) a tailor-made binding or reactive site and (ii) a colorimetric event. For the former we selected the suitable properties of 2-(2-(dimethylamino)phenyl)ethanol derivatives (see Scheme 1). This group contains a nucleophile, the hydroxyl moiety, which is known to undergo acylation reactions with phosphonate substrates to form intermediate II that suffers a rapid intramolecularN-alkylation to yield III, a quaternary ammonium salt. Remaining with the versatility of the last approach and at the same time being interested in the design of colorimetric probes we envisioned that the coupling of the dimethylaminophenyl donor group with an acceptor moiety (A) could be a suitable approach for the design of tailor-made colorimetric probes for nerve agents’ detection. We expected that the conversion of the tertiary amine I to the quaternary ammonium III upon reaction with certain organophosphorus (OP) substrates would dramatically change the electronic donor properties of the nitrogen atom thus resulting in a decrease of the push–pull character of the dye and in a colour modulation. As a proof-of-the-concept and using 2-(2-(dimethylamino)phenyl)ethanol (DAPE) as a building block we prepared the chromoreactand 1 (see Scheme 2).z The starting compound DAPE was synthesized from 2-nitrotoluene that was in a first step converted into 2-(2-nitrophenyl)ethanol following a previously described method. Then, a reductive amination in the presence of formaldehyde gives rise to 2-(2-(dimethylamino)phenyl)ethanol. The new probe 1 was prepared from the reaction of DAPE with the diazonium salt of 4-nitroaniline using known procedures for the preparation of azo dyes. As a first step, the reactivity of 1 was tested with diethyl chlorophosphate (DCP), diisopropyl fluorophosphate (DFP) and diethyl cyanophosphate (DCNP) in acetonitrile. These organophosphates have been widely used as simulants as they display a reactivity similar to that of nerve agents such as Tabun, Sarin and Soman, yet they lack their toxicity. Acetonitrile solutions of chromoreactand 1 display an absorption spectrum typical of azo dyes with an intense absorption band (log e 44) at 410 nm. This yellow band has a charge-transfer character due to the presence of an electron donor anilinium group and a nitrophenyl moiety acting as electron acceptor. Upon addition of 100 equiv. of DCP to acetonitrile solutions of chromoreactand 1 a hypsochromic shift of 85 nm (Fig. 1) was observed that resulted in a modulation from yellow to colourless. This shift to shorter wavelengths is consistent with the intramolecular cyclization process; i.e. the N,N-dimethylanilino moiety drastically reduces its donor character