Challenges in Fluorescence Detection of Chemical Warfare Agent Vapors Using Solid-State Films Shengqiang Fan, Guanran Zhang, Genevieve H. Dennison, Nicholas Fitzgerald, Paul L. Burn, Ian R. Gentle*, Paul E. Shaw* Dr S. Fan, Dr G. Zhang, Prof. P. L. Burn, Prof. I. R. Gentle, Dr P. E. Shaw Centre for Organic Photonics and Electronics, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia Email: [email protected]; [email protected] Dr G. H. Dennison, Dr N. Fitzgerald Defence Science & Technology Group, Land Division, Fishermans Bend, Vic 3207, Australia Keywords: nerve agent simulant, hydrolysis, fluorescence, sensing, solid-state Organophosphorus (OP)-based nerve agents are extremely toxic and potent acetylcholinesterase inhibitors and recent attacks involving nerve agents highlight the need for fast detection and intervention. Fluorescence-based detection, where the sensing material undergoes a chemical reaction with the agent causing a measurable change in the luminescence, is one method for sensing and identifying nerve agents. Most studies use the simulants diethylchlorophosphate (DCP) and di- iso-propylfluorophosphate (DFP) to evaluate the performance of sensors due to their reduced toxicity relative to the OP nerve agents. While detection of nerve agent simulants in solution is relatively widely reported there are fewer reports on vapor detection using solid-state This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/adma.201905785. This article is protected by copyright. All rights reserved. sensors Herein progress in organic semiconductor sensing materials developed for solid-state detection of OP-based nerve agent vapours is reviewed. Also the effect of acid impurities arising from the hydrolysis of simulants and nerve agents on the efficacy and selectivity of the reported sensing materials is discussed. Indeed, in some cases it is unclear whether it is the simulant that is detected or the acid hydrolysis products. Finally, we highlight that while analyte diffusion into the sensing film is critical in the design of fast, responsive sensing systems, it is an area that is currently not well studied. 1. Introduction Chemical warfare agents (CWAs) can be classified by their physiological effects into several groups, including nerve, blister, blood, choking, harassing, and incapacitation agents, and toxins.[1] Whilst the use of CWAs is banned and access to precursors tightly controlled, the relative ease of synthesis of some CWAs means they are potentially accessible to terrorist groups or rogue nation states, and still pose a real threat to public safety and national security.[2] Among CWAs, nerve agents are a family of highly toxic organophosphorus (OP) compounds.[3] The main routes of exposure are via inhalation or the skin and their mode of action is inhibition of the enzyme acetylcholinesterase (AChE), which is critical for hydrolysing the neurotransmitter acetylcholine to control its concentration.[4] The inhibition of AChE leads to an accumulation of acetylcholine and results in muscle overstimulation. Nerve agents are generally divided into two series, G and V (Figure 1). G-series including tabun (GA), sarin (GB), soman (GD) and cyclosarin (GF) were first developed before and during World War II by German chemists. The V-series were synthesised later (1950s) by the British and weaponised by the American military. Compared to the G-series, the V-series are more persistent in the environment This article is protected by copyright. All rights reserved. 2 due to them being slower to hydrolyse and less volatile.[5] In addition, the V-series are more toxic, [5] with LD50 (lethal dose, 50%) values 1-2 orders of magnitude lower than the G-series. Sarin was reportedly used in the recent Syrian civil war several times and VX was used in the assassination of Kim Jong-Nam in 2017,[6] and hence sadly there is still a need to be able to rapidly detect nerve agents and CWAs more generally. Figure 1 Structures of nerve agents (G- and V-series) and simulants. Nerve agents are odourless and colorless when pure and development of detection technologies that can meet the needs of military, first responders (national security), healthcare and environmental monitoring agencies is a continuing challenge. A variety of detection methods have been developed including gas chromatography-mass spectroscopy (GC-MS),[7] enzyme-based biosensors,[8-10] chemiresistors,[11-13] and surface acoustic wave (SAW) sensors.[14,15] These detection systems are either slow, complex, nonselective, or the equipment is too cumbersome for field use. This article is protected by copyright. All rights reserved. 3 An alternative detection method is optical-based sensing, that is, to use a material whose absorption or emission changes by reaction with the nerve agents. Potential advantages of optical detection include portability of the equipment, real-time monitoring, and rapid and selective detection. If the functionality on the sensing material is carefully chosen to specifically react with a nerve agent, optical detection will be less susceptible to interferents. Fluorescence-based detection has several potential advantages over colorimetric detection in terms of speed, sensitivity, and mode of detection. Fluorescence-based detection can be achieved using a change in the steady-state photoluminescence (PL) intensity (“turn on” or “turn off”), PL color (as shown in Figure 2), or PL lifetime. Therefore, it is possible to monitor multiple characteristics of the PL simultaneously (e.g., color and intensity) to improve selectivity. Figure 2 Illustration of fluorescence-based detection of CWAs through a PL color change, (i)(ii), or a PL intensity change, (ii)(iii). It will be appreciated that due to the toxicity of nerve agents and their restricted availability, testing sensing materials against real agents can only be undertaken in OPCW declared facilities. To aid the development of new sensing materials their performance is typically evaluated using simulants that This article is protected by copyright. All rights reserved. 4 are reported to have lower toxicity. This perspective will focus on the detection of the G-series nerve agents for which diethylchlorophosphate (DCP) and di-iso-propylfluorophosphate (DFP) are the two widely used simulants for Sarin (GB), Soman (GD) and cyclosarin (GF) that contain a P-F bond, with diethylcyanophosphate (DCNP) being the simulant for Tabun (GA) which is comprised of a P-CN bond. It should be noted that although DCP is a much more popular simulant than DFP, whether it is appropriate to simulate the P-F bond of the G-agents (sarin, soman and cyclosarin) is questionable as the P-Cl (326 kJ/mol) and P-F (490 kJ/mol) bond strengths are markedly different. 2. Solid-state fluorescence sensing of nerve agent and simulant vapors The majority of reported studies on the fluorescence-based detection of nerve agents have been done in solution with fewer reports describing solid-state sensors. In general, sensing materials are designed to have nucleophilic functional groups that purportedly attack the phosphorous atom leading to subsequent displacement of the cyanide moiety for GA and fluoride for GB, GD and GF and attachment of the “nerve agent” to the sensing compound. In an alternative strategy, the sensing materials may have functionality that enables co-ordination with the P=O functional group to give distinct changes in the PL characteristics. Several recent reviews discuss the myriad of different materials reported for nerve agent and simulant sensing;[16-20] hence, only those materials that are reported in the context of vapor phase detection using solid-state films will be discussed here. Vapor phase detection using solid-state films is the most practicable approach for detecting nerve agents in the field. The sensing materials and their performance in solid-state vapor detection are summarised in Table 1, with their molecular structures shown in Figures 3-6. Table 1 Summary of sensing performance of materials that have been examined for the detection of nerve agent simulant vapors using solid-state films. The molecular structures of the materials listed This article is protected by copyright. All rights reserved. 5 in this table are shown in Figures 3, 4, 5 and 6. (TEP – triethyl phosphate; TEA – triethylamine; PEO – polyethylene oxide; PVP – poly(4-vinylpyridine); DMAP – 4-dimethylaminopyridine; DMMP – dimethyl methylphosphonate; CA – cellulose acetate; PS – polystyrene) Reporter Matrix or Analyte Limit of Selectivity and compound Sensor Proposed mechanism substrate vapors detection sensitivity isolated & characterised Coordination with 1a, Not False positive Silica particle TEP La3+ and Eu3+ to free Yes 1b[21] stated from TEA the fluorescent ligands N-protonation to give False positives 8 nM 2[22] PEO DCP strong intramolecular from AcOH and No solution charge transfer (ICT) HCl Spin-coated 2.6 ppb False positive 3[23] DCP As 2 No on quartz vapor from HCl Selective to DCP 1.82 ppb cf non-halogen 4[24] Filter paper DCP As 2 No vapor OP compounds such as TEP Spin-coated 0.14 ppb False positive 5[25] DCP As 2 No on quartz vapor from HCl Amine Films showed Polymer phosphorylation to Not selective 6[26] microbeads DCP reduce photoinduced