Detection Papers with Metal Complexes with Triphenylmethane Dyes for the Detection of G-Series Nerve Agents (Sarin, Soman, Cyclosarin) in the Liquid Phase

chemosensors

Article Detection Papers with Metal Complexes with Triphenylmethane Dyes for the Detection of G-Series Nerve Agents (Sarin, Soman, Cyclosarin) in the Liquid Phase

Martin Lobotka 1,*, Vladimír Pitschmann 1,2 and Lukáš Matˇejovský 3

1 Oritest spol. s r.o., Nábˇrežní 90/4, 150 00 Prague, Czech Republic; [email protected] 2 Faculty of Biomedical Engineering, Czech Technical University in Prague, námˇestí Sítná 3105, 272 01 Kladno, Czech Republic 3 Faculty of Environmental Technology, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic; [email protected] * Correspondence: [email protected]

Received: 11 October 2019; Accepted: 25 November 2019; Published: 27 November 2019

Abstract: The paper presents the results of the study of the possibilities of using color metal complexes to detect the presence of chemical warfare agents (CWA) in liquid or aerosol form. Aluminon/Fe3+ and Eriochrome Cyanine R/Cu2+ coordination complexes and their ability to detect CWA in liquid phase are discussed. Detection systems have been demonstrated on instances of simple detection papers exposed to drops of real CWAs. Detection papers showed a positive response to G-series nerve agents and vesicant lewisite. Other liquid CWA do not interfere and the systems are also resistant to common organic solvents and a wide range of industrial chemicals.

Keywords: metal complexes; triphenylmethane dyes; chromogenic chemosensors; CWA detection; G-series nerve agents

1. Introduction The most important group of chemical warfare agents (CWA) are nerve agents whose toxic effect is based on the inhibition (blockade) of the acetylcholinesterase. This enzyme is involved in the transmission of nerve excitation using the neurotransmitter acetylcholine [1]. Chemically, there are several groups of organophosphorus compounds; the most well-known are alkyl/cycloalkyl-methylphosphonofluoridates (sarin GB, soman GD, cyclosarin GF, all with P-F bond) and ethyl-(dimethylphosphoroamido) cyanidate (tabun GA, with P-CN bond). Although the so-called G-series nerve agents do not reach the toxicity of V-series nerve agents (VX, RVX, with P-S bond), their easier preparation and physical and chemical properties increase the risk of abuse for terrorist and criminal targets [2,3]. The basic measure of protection against them is fast, high-quality, and widely available detection. Main attention is paid to their vapor detection, because vapors pose a high risk of inhalation poisoning, especially by the volatile GB (boiling point 150 ◦C). Much less attention is paid to their detection in the form of droplets and aerosols, which can also cause severe percutaneous poisoning; particularly dangerous are the semi-persistent agents GD and GF (boiling point 198 ◦C, resp. 228 ◦C). The simplest yet highly effective method of detection of CWA droplets and aerosols is based on the use of detection papers by visual evaluation (the naked eye) of color changes. For example, 3-WAY detection paper is currently used worldwide to detect and differentiate vesicant mustard gas (HD) and G-series and V-series nerve agents. Color changes are due to the solubility of specific dyes in liquid CWA; in the case of G-series nerve agents it is disperse

Chemosensors 2019, 7, 59; doi:10.3390/chemosensors7040059 www.mdpi.com/journal/chemosensors Chemosensors 2019, 7, 59 2 of 10 yellow (CAS: 6250-23-3) providing a yellow color. The disadvantage is its very low selectivity as many organic solvents and other industrial chemicals give the same or similar color [4,5]. It is worth mentioning that CWA detection can be also realized by advanced instrumental methods, for example, Raman spectroscopy [6,7]. However, these analytical methods do not compete with inexpensive simple detection papers, which, in addition, enables to detect primary droplet and aerosols, characteristic for chemical attack or other (emergency) leak of liquid CWAs to the environment. Raman spectroscopy and other instrumental methods are suitable for subsequent control of the presence of CWA and its identiﬁcation (usually after necessary sample treatment). The strategy for further development of detection papers enabling the detection of G-series nerve agents can be based on the application of various chemosensors that have been developed in a number of workplaces around the world in recent years [8–11]. A special group of these chemosensors are color metal complexes with some organic ligands that decompose and discolor by the action of organophosphorus CWA [9,12–18]. In the past, the study of these complexes was mainly focused on detection in the gas phase, but they can also be very useful for solving problems of detection of droplets and aerosols. The aim of this paper is to report the results of research into the possibility of preparing detection papers for liquid G-series nerve agents, which are based on color complexes of metal cations with triphenylmethane dyes, in this case Aluminon and Eriochrome Cyanine R. The complexes of these dyes are well known in analytical chemistry [19,20], but their use for detecting highly toxic organophosphorus substances is new and appears to be promising.

2. Experimental Section

2.1. Chemicals and Materials Ferric chloride hexahydrate, copper(II) chloride, Aluminon (C.I. 43810, ALU), Eriochrome Cyanine R (C.I. 43820, ECR), glycerol (all Sigma-Aldrich, St. Louis, MO, USA), and distilled water were used to prepare detection papers. To check the functionality of the detection papers, these CWA were used: Tabun (GA), sarin (GB), soman (GD), VX agent, sulphur mustard (HD), nitrogen mustards (HN-1 and HN-2), lewisite (L), lewisite analogs (L-2, L-3), diphosgene (DP), all Military Research Institute, Brno, Czech Republic), and simulation agent (mimic) diethyl chlorophosphate (DCP, Sigma-Aldrich). White cellulose cardboard paper with a nominal basis weight of 300 g/m2 and a thickness of 1 mm and ashless ﬁlter paper for quantitative analysis Whatman 589/3 were used as a carrier of the color complex (Whatman, Kent, UK). An Accumet AB-150 pH meter with a combined electrode (Fischer Scientiﬁc, Pardubice, Czech Republic) were used for the pH measurement. An LMG 173 portable tristimulus colorimeter was used to assess the stability of the detection paper (Dr. Lange, Dusseldorf, Germany). Spectrophotometric measurement (absorption spectra) were performed using a spectrophotometer Aquamate (Thermo Spectronic, Cambridge, UK).

2.2. Preparation of Detection Papers Based on the evaluation of the pilot tests, detection papers based on two complexes were prepared for further research: ALU/Fe3+ and ECR/Cu2+. The 100 50 mm ﬁlter paper blocks were immersed in × 100 mL of the impregnation solution containing:

1 0.05% of ALU, 0.02% of ferric chloride hexahydrate, and 10% of glycerol in distilled water, 2 0.15% of ECR, 0.5% of copper(II) chloride, and 10% of glycerol in distilled water.

After impregnation the carrier with the solution of the complexes, the paper was dried at 20 ◦C for 24 h. Chemosensors 2019, 7, 59 3 of 10

2.3. Functionality Testing Droplets of test substances (CWA, simulants, interfering chemicals) with a volume of 10 µL were dosed on the detection paper by a micropipette and changes in its color were observed visually (by the naked eye). The evaluation was performed within 2 min by default. Each test was repeated 3 times (for CWA on 2 lots). The detection papers were stored in the laboratory freely in the air at 21–23 ◦C for 6 months. A part of the sample was stored in an oven at 80 ◦C for 1 month to assess the thermal stability of the detection system. Changes in their appearance and functionality on DCP droplets were monitored at regular intervals. The change in appearance was followed by the tristimulus colorimeter using the ∆E parameter, which can be expressed by the equation ∆E = [(∆L*)2 + (∆a *)2 + (∆b*)2]1/2, where ∆L*, ∆a*, and ∆b* are diﬀerences between individual values of L*, a*, and b* of standard and controlled color (L* represents the neutral brightness axis; a*, the chromatic green-red axis; and b*, the chromatic blue-yellow axis).

3. Results and Discussion

3.1. Pilot Tests The research was focused on metal complexes triphenylmethane dyes that contain carboxyl groups as electron donors. Al3+, Fe3+, Zn2+ and Cu2+ were tested as metal cations, and then ALU, ECR, and xylenol orange (XO) were tested as ligands. The selection of complexes, without further modiﬁcation, is shown in Table1. It is evident that the complexes mentioned in this table reacted most frequently to GB, and on the contrary they did not respond to VX and HD at all (except for XO/Zn2+). Part of the complexes gave a positive response to L.

Table 1. Pilot tests of chemical warfare agents (CWAs) with metal complexes with triphenylmethane dyes the without addition of glycerol (- no change).

Change of Colour with CWA in Liquid Phase Complex Original Colour GA GB VX HD L ALU/Al3+ Red - lightening - - - ALU/Fe3+ violet - lightening - - orange ALU/Zn2+ Red - lightening - - - ECR/Cu2+ Blue orange orange - - orange ECR/Al3+ violet orange orange - - orange XO/Fe3+ Blue - pink - - orange XO/Al3+ Pink - yellow - - - XO/Zn2+ Red yellow yellow Pink pink -

3.2. pH Study of Color Complexes For metal complexes, color dependence on pH is typical. This has also been conﬁrmed in the color complexes of triphenylmethane dyes, potentially suitable for CWA detection. Taking into account the results given in Table1, two complexes covering the pH 2–12 region, namely the ALU /Fe3+ and ECR/Cu2+ complexes (chemical structures of selected dyes ALU and ECR are shown in Figure1), were selected for further experiments on the basis of a pH study in aqueous solutions. For analytical purposes, the acid form of ALU/Fe3+ and the neutral and alkaline forms of ECR/Cu2+ are suitable. The pH-dependent color changes of both complexes are illustrated in Figure2. Chemosensors 2019, 7, 59 4 of 10 Chemosensors 2019, 7, 59 4 of 10

(a) (b)

Figure 1. Structures of selected triphenylmethanetriphenylmethane dyes: ALU ( a) and ECR (b).

(a) (b)

Figure 2.2. Change of ALUALU/Fe/Fe33++ ((aa)) and and ECR/Cu ECR/Cu2+2+ (b(b) )metal metal complexes complexes depending depending on on the the pH ofof aqueous solution.

Increased attentionattention has has been been paid paid to theto the possibilities possibilities of eliminating of eliminating the eﬀ theect ofeffect pH onof thepH stability on the andstability functionality and functionality of the complexes. of the complexes. The problem The is thatproblem the complexes is that the behave complexes diﬀerently behave on differently the carrier (celluloseon the carrier paper), (cellulose than in paper), solution. than However, in solution. this However, has no major this impact has no onmajor the practicalimpact on application the practical of theapplication proposed of method the proposed because method the (total) because discoloration the (total) of discoloration the complex isof used the complex as an analytical is used signal, as an notanalytical just a changesignal, innot its just color. a change in its color.

3.3. Detection/Reaction Principle 3.3. Detection/Reaction Principle The detection system itself is likely to consist of several forms of metal complexes that cannot The detection system itself is likely to consist of several forms of metal complexes that cannot be described by one exact structure; various forms of aqua complexes of triphenylmethane dyes and be described by one exact structure; various forms of aqua complexes of triphenylmethane dyes otherand other structures structures have beenhave previouslybeen previously described desc [ribed21–26 ].[21–26]. The structure The structure of the complexes of the complexes will depend will (amongdepend other(among things) other onthings) the pH on of the the pH environment. of the environment. The principle The principle of detecting of detecting G nerve agentsG nerve is based on their reaction (or set of reactions, including esteriﬁcation) with ALU/Fe3+ and ECR/Cu2+ agents is based on their reaction (or set of reactions, including esterification) with ALU/Fe3+ and complexes resulting in their decomposition associated with discoloration. This is shown in Figure3, ECR/Cu2+ complexes resulting in their decomposition associated with discoloration. This is shown 3+ whichin Figure contains 3, which the contains absorption thespectra absorption of the spectra dyes (ALU,of the dyes ECR), (ALU, their metalECR), complexestheir metal (ALUcomplexes/Fe , ECR/Cu2+), and their reaction products with DCP. This decomplexation was experimentally conﬁrmed (ALU/Fe3+, ECR/Cu2+), and their reaction products with DCP. This decomplexation was in the ALU/Fe3+ system by the presence of free Fe3+ ions through an analytical reaction leading to experimentally confirmed in the ALU/Fe3+ system by the presence of free Fe3+ ions through an analytical reaction leading to Prussian blue (Figure 4). It was found that the rate and degree of decomplexation was significantly increased by the addition of high-boiling alcohols (glycerol, Chemosensors 2019, 7, 59 5 of 10

Chemosensors 2019,, 77,, 5959 5 of 10 Prussian blue (Figure4). It was found that the rate and degree of decomplexation was signiﬁcantly increasedtriethylene by glycol, the addition polyethylene of high-boiling glycol), alcohols but the (glycerol, mechanism triethylene of their glycol, effect polyethylene has not yet glycol), been butexplained the mechanism in detail. of their eﬀect has not yet been explained in detail.

1 ALU 0.9 ALU/DCP 0.8 ALU/Fe3+ ALU/Fe3+/DCP 0.7

0.6

0.5

0.4 Absorbance Absorbance 0.3

0.2

0.1

0 400 450 500 550 600 Wavelength (nm) (a) 1.4 ECR ECR/DCP 1.2 ECR/Cu2+ ECR/Cu2+/DCP 1

0.8

0.6 Absorbance Absorbance 0.4

0.2

0 400 450 500 550 600 Wavelength (nm) (b)

Figure 3.3. Absorption spectra: ( aa)) ALU, ALU/Fe ALU/Fe3+3+,, ,andand and theirtheir their reactionreaction reaction productsproducts products withwith with DCP;DCP; DCP; (( (bb)) ECR, ECRECR/Cu/Cu22++,, , andand and theirtheir their reactionreaction reaction productsproducts products withwith with DCP.DCP. DCP.

(a) (b) (c) (d)

3+ Figure 4.4. SimpleSimple proof proof of of free free Fe Fe3+ions ionsions using usingusing the thethe Prussian PrussianPrussian blue blueblue method: method:method: (a) Unexposed ((a) Unexposed detection detection paper 3+ ALUpaper/Fe ALU/Fe,(b) drop3+,, ((b) of drop potassium of potassium ferrocyanide, ferrocyanide, (c) drop (c of) drop diethyl of diethyl chlorophosphate chlorophosphate (DCP), ((DCP),d) drop (d of) DCPdrop andof DCP potassium and potassium ferrocyanide. ferrocyanide. 3.4. Color Reactions with CWA, and Interferences 3.4. Color Reactions with CWA, and Interferences Detection papers with ALU/Fe3+ and ECR/Cu2 complexes have been tested on virtually all major Detection papers with ALU/Fe3+ and ECR/Cu2 complexes have been tested on virtually all CWA in liquid form. As it can be seen in Figure5, particularly positive reactions with both complexes major CWA in liquid form. As it can be seen in Figure 5, particularly positive reactions with both complexes were found for nerve agents GB, GD, and GF (all with P-F bond). The detection paper with the ALU/Fe3+ complex was very well distinguished from vesicant L, which gave a distinctive orange color, while GB, GD, and GF caused complete discoloration. GA (with P-CN bond) gave a Chemosensors 2019, 7, 59 6 of 10

Chemosensorswere found 2019 for, 7, nerve59 agents GB, GD, and GF (all with P-F bond). The detection paper with6 of the 10 ALU/Fe3+ complex was very well distinguished from vesicant L, which gave a distinctive orange color, positivewhile GB, response GD, and only GF causedto ECR/Cu complete2+ complex discoloration. detection GA paper, (with but P-CN less bond) clearly gave than a positive other G response nerve 2+ agents.only to HD, ECR /HN-1,Cu complex HN-2, and detection VX did paper, not butrespond less clearly to any than detection other G paper; nerve agents.DP reacted HD, in HN-1, an indistinctiveHN-2, and VX way. did not respond to any detection paper; DP reacted in an indistinctive way.

GD GB GF GA VX DP

HD L L-2 L-3 HN-1 HN-2

3+ ALU/Fe

BAET 5% HNO3 2% NaOH BzCl DMEA Acetone

GD GB GF GA VX DP

HD L L-2 L-3 HN-1 HN-2

2+ ECR/Cu

BAET 5% HNO3 2% NaOH BzCl DMEA Acetone

FigureFigure 5. 5. OfOf CWA CWA reactions and selected chemicalschemicals withwith detectiondetection paperpaper ALUALU/Fe/Fe33++ and ECRECR/Cu/Cu2+2+ (BAET(BAET == 2-(butylamino)ethanethiol,2-(butylamino)ethanethiol, BzCl BzCl == benzoylbenzoyl chloride, chloride, DMEA DMEA == NN,N,N-dimethylethanolamine).-dimethylethanolamine).

BothBoth systemssystems areare inert inert to conventionalto conventional organic orga solventsnic solvents (ethanol, (ethanol, methanol, methanol, acetone, acetonitrile, acetone, acetonitrile,toluene, chloroform, toluene, liquidchloroform, hydrocarbons, liquid hydrocarbons, petrol, carbon petrol, disulphide) carbon as disulphide) well as to water;as well no as color to water;change no was color observed. change was In both observed. systems In thereboth issystem a clears there interference is a clear of interference acids and bases of acids (in theand case bases of (inALU the/Fe case3+ the of ALU/Fe effect of3+ bases the effect corresponds of bases wellcorresponds with the well pH studywith the (see pH Figure study2 )).(see The Figure influence 2)). The of influencesome industrial of some chemicals industrial selected chemicals for their selected structural for their similarity structural to some similarity CWA was to some different CWA for eachwas differentdetection for paper each variant. detection As shownpaper invariant. Figure 5As, the shown detection in Figure paper 5, with the the detection ALU /Fe paper3+ complex with wasthe ALU/Feclearly more3+ complex resistant was to clearly these interferences.more resistant to these interferences. FromFrom experimentalexperimental datadata it canit can be partiallybe partially concluded concluded that the that proposed the proposed method hasmethod good has selectivity good selectivity(the distinction (the ofdistinction G-type nerve of substancesG-type nerve from substances other CWAs from is significant) other CWAs and relativelyis significant) resistant and to relativelyinterferences resistant that mayto interferences occur in real that conditions. may occur In thisin real aspect, conditions. the proposed In this methodaspect, the is much proposed more method is much more selective and resistant than current commercial solutions. However, a detailed study of the entire spectrum of potential interferences (including various chemical mixtures) is planned as part of the industrial development of new detection paper. Chemosensors 2019, 7, 59 7 of 10 selective and resistant than current commercial solutions. However, a detailed study of the entire spectrum of potential interferences (including various chemical mixtures) is planned as part of the Chemosensors 2019, 7, 59 7 of 10 industrial development of new detection paper.

3.5. Color Color Stability Stability The stability of the coloration (discoloration) at at th thee site of exposure is very high, no reversible reaction was observed even after severalseveral hours.hours. The The discolored discolored stains stains are are also also visible after the immersionimmersion of the detection paper in the water for 24 h.

3.6. Limit Limit of of Detection Detection The detection limit was expressed as as the concentration of of DCP, DCP, when a positive reaction was visible withinwithin 22 minmin after after dispensing dispensing 10 10µ LµL of of the the solution. solution. This This condition condition was was also also realized realized in a 3.5%in a 3.5%DCP DCP solution solution in hexane, in hexane, i.e., about i.e., about 0.35 mg0.35 of mg DCP of DCP (Figure (Figure6). A 6). detection A detection limit limit of less of thanless 0.35than 0.35mg canmg becan achieved be achieved by extending by extending the color the color change change evaluation evaluation time (time>2 min). ( >2 min). Just to Just assume: to assume: LD50 LD(percutaneously,50 (percutaneously, liquid) liquid) of GA of isGA 1500 is 1500 mg, GBmg, 1700 GB 1700 mg, mg, GD andGD and GF 350GF mg350 (DCPmg (DCP estimated estimated in the in theorder order of 10,000 of 10,000 mg). mg). In general, In general, the ratethe rate of discoloration of discoloration depends depends on the on analytethe analyte concentration. concentration. The Theundiluted undiluted DCP reactedDCP reacted almost almost immediately immediately (within 5(w s),ithin with 5 itss), dilution with its the dilution rate of discolorationthe rate of discolorationdecreased, (the decreased, time needed (the time to discolor needed the to detectiondiscolor the paper detection increased). paper Inincreased). this context, In this it iscontext, worth itnoting is worth that noting the decomplexation that the decomplexation due to DCP due is faster to DCP than is the faster decomplexation than the decomplexation due to G nerve due agents to G nervewith the agents structure with the of alkyl structure/cycloalkyl-methylphosphonoﬂuoridates of alkyl/cycloalkyl-methylphosphonofluorida (as a resulttes of (as the a diresultﬀerence of the in 2+ differencereactivity ofin P-Clreactivity and P-F of bonds).P-Cl and ECR P-F/Cu bonds).detection ECR/Cu paper2+ detection is completely paper discoloredis completely (white) discolored due to (white)DCP, unlike due to G DCP, nerve unlike agents, G where nerve paleagents, pink where to orange pale pink color to appears. orange color appears.

100 90 80 70

60 ECR/Cu2+ E

Δ 50 ALU/Fe3+ 40 30 20 10 0 0 102030405060708090100 Concentration of DCP (%) Figure 6. Dependence ofof discolorationdiscoloration ofof detection detection papers papers (∆ (E)ΔE) on on DCP DCP concentrations concentrations (measured (measured by bytristimulus tristimulus colorimeter colorimeter after after 2 min 2 min of reaction).of reaction).

3.7. Stability of Detection Papers 3.7. Stability of Detection Papers ALU/Fe3+ and ECR/Cu2+ detection papers stored for 6 months at laboratory temperature retained ALU/Fe3+ and ECR/Cu2+ detection papers stored for 6 months at laboratory temperature their original appearance and functionality. Interesting results were obtained when they were stored at retained their original appearance and functionality. Interesting results were obtained when they 80 C. Figure7 shows considerable di ﬀerences in the thermal stability (appearance) of the detection were◦ stored at 80 °C. Figure 7 shows considerable differences in the thermal stability (appearance) papers and a very good stability of the ALU/Fe3+ system. This ﬁnding corresponds to the observed of the detection papers and a very good stability of the ALU/Fe3+ system. This finding corresponds functional stability (Figure8). The ALU /Fe3+ detection paper provided a complete discoloration almost to the observed functional stability (Figure 8). The ALU/Fe3+ detection paper provided a complete immediately after the application of 10 µL of DCP, regardless of the heat load time; the rate and degree discoloration almost immediately after the application of 10 µL of DCP, regardless of the heat load time; the rate and degree of discoloration were virtually unchanged from the standard (stored at laboratory temperature). The ECR/Cu2+ detection paper showed a decrease in functionality compared to the standard; discoloration was slower and less marked (no complete discoloration). Chemosensors 2019, 7, 59 8 of 10

of discoloration were virtually unchanged from the standard (stored at laboratory temperature). The ECR/Cu2+ detection paper showed a decrease in functionality compared to the standard; discoloration Chemosensors 2019, 7, 59 8 of 10 wasChemosensors slower 2019 and, 7 less, 59 marked (no complete discoloration). 8 of 10

35 35

30 30

25 25

20 ALU/Fe3+ E 20 ALU/Fe3+ E Δ Δ 15 ECR/Cu2+ 15 ECR/Cu2+

10 10

5 5

0 0 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 Time (day) Time (day) Figure 7. Stability (ALU/Fe3+3,+ ECR/Cu2+,2 +detection papers appearance) at 80 °C; ΔE measured by Figure 7.7. StabilityStability (ALU(ALU/Fe/Fe 3+,, ECR/Cu ECR/Cu2+, ,detection detection papers papers appearance) appearance) at at 80 80 °C;◦C; Δ∆E measured by tristimulustristimulustristimulus colorimeter. colorimeter.colorimeter.

Exposure Thermal load time (days), 80 oC Exposure Thermal load time (days), 80 oC DCP (min) 0 7 14 21 28 DCP (min) 0 7 14 21 28

1 1

3+ 3+ 2 2 ALU/Fe ALU/Fe

5 5

1 1

2+ 2+ 2 2 ECR/Cu ECR/Cu

5 5

FigureFigure 8. 8. Tested Tested with with DCP DCP after after heat heatheat load loadload at atat 80 8080 °C ◦°CC within within 28 28 days. days.

4.4. Conclusions Conclusions MetalMetal complexescomplexes representrepresent a a promisingpromising developmentaldevelopmental direction direction inin the the fieldfield ofof qualitativequalitative 3+ detectiondetection of of CWA CWA in in liquid liquid or or aerosol aerosol form. form. The The proposed proposed simple simple detection detection systems, systems, ALU/Fe ALU/Fe3+ and and 2+ ECR/CuECR/Cu2+, ,consisting consisting of of commonly commonly used used and and cheap cheap reagents, reagents, were were able able to to detect detect G G nerve nerve agents agents Chemosensors 2019, 7, 59 9 of 10

4. Conclusions Metal complexes represent a promising developmental direction in the field of qualitative detection of CWA in liquid or aerosol form. The proposed simple detection systems, ALU/Fe3+ and ECR/Cu2+, consisting of commonly used and cheap reagents, were able to detect G nerve agents with very good selectivity; only lewisite reacted differently from other potential CWA. Taking into account the structure of positively reacting substances, it is likely that other compounds with P-X bond (X = F, Cl) will also react similarly, i.e., for example, extremely toxic substances from the Novichok group [4]. In particular, ALU/Fe3+ detection paper is suitable for the detection of these substances in the liquid phase even in extremely difficult climatic conditions. The relatively high stability of the metal complexes allows wide modifications, where substances (such as glycerol or other hydroxy compounds) can be added to the color indicators to accelerate or enhance color change. This offers further possibilities in determining or adjusting the selectivity of the reactions. Such a solution represents a certain departure from the established detection means which use mostly chemically reactive compounds, and in the case of organophosphates also biochemical reactions.

Author Contributions: Conceptualization: V.P. and M.L.; Methodology: V.P., M.L. and L.M.; Formal analysis: M.L. and L.M.; Validation: VP, M.L. and L.M.; Writing—manuscript preparation: M.L. and V.P.; Writing—review and editing: V.P., M.L. and L.M; Resources: V.P.; project supervisor: V.P. Funding: The work was funded in the framework of a security research project of the Ministry of Interior of the Czech Republic, No. VI20172019101. Conﬂicts of Interest: The authors declare that they have no competing interest.

References

1. Costanzi, S.; Machado, J.H.; Mitchell, M. Nerve agents: What they are, how they work, how to counter them. ACS Chem. Neurosci. 2018, 9, 873–885. [CrossRef][PubMed] 2. Potential Military Chemical (Biological) Agents and Compounds; Field Manual FM 3-11.9; Exidyne: Wentzeville, MO, USA, 2005. 3. Franke, S. Lehrbuch der Militärchemie; Militärverlag der DDR: Berlin, Germany, 1977; Volume 2v. 4. Halámek, E.; Kobliha, Z.; Pitschmann, V. Analysis of Chemical Warfare Agents; University of Defence: Brno, Czech Republic, 2009. 5. Thoraval, D.; Bovenkamp, J.W. Paper Chemical Agent Detectors, EP 0 334 668 B1, 23.12. 1992. Available online: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web& cd=3&ved=2ahUKEwix0eLj6onmAhXhx6YKHdJhANcQFjACegQIBRAC&url=https%3A%2F% 2Fpatentimages.storage.googleapis.com%2Fpdfs%2F57050eab456edfc3d6e9%2FEP0334668B1.pdf& usg=AOvVaw3RvGj0EAJta9K2rwuhUDtY (accessed on 28 November 2019). 6. Galan-Freyle, N.J.; Figueroa-Navedo, A.M.; Pacheco-Londoño, Y.C.; Ortiz-Rivera, W.; Pacheco-Londoño, L.C.; Hernández-Rivera, S.P. Chemometrics-enhanced fiber optic Raman detection, discrimination and quantification of chemical agents simulants concealed in commercial bottles. Anal. Chem. Res. 2014, 2, 15–22. [CrossRef] 7. Hu, G.; Xiong, W.; Luo, H.; Shi, H.; Li, Z.; Shen, J.; Fang, X.; Xu, B.; Zhang, J. Raman spectroscopic detection for simulants of chemical warfare agents using a spatial heterodyne spectrometer. Appl. Spectrosc. 2018, 72, 151–158. [CrossRef][PubMed] 8. Royo, S.; Martinez-Máñez, R.; Sancenón, F.; Costero, A.M.; Parra, M.; Gil, S. Chromogenic and fluorogenic reagens for chemical warfare nerve agents detection. Chem. Commun. 2007, 4839–4847. [CrossRef] 9. Chen, L.; Wu, D.; Yoon, J. Recent advances in the developments of chromophore-based chemosensors for nerve agents and phosgene. ACS Sens. 2018, 3, 27–43. [CrossRef] 10. Kangas, M.J.; Burks, R.M.; Atwater, J.; Lukowicz, R.M.; Williams, P.; Holmes, A.E. Colorimetric sensor arrays for the detection and identification of chemical weapons and explosives. Crit. Rev. Anal. Chem. 2017, 47, 138–153. [CrossRef] Chemosensors 2019, 7, 59 10 of 10

11. Pitschmann, V.; Matˇejovský, L.; Lunerová, K.; Dymák, M.; Urban, M.; Králík, L. Detection papers with chromogenic chemosensors for direct visual detection and distinction of liquid chemical warfare agents. Chemosensors 2019, 7, 30. [CrossRef] 12. Knapton, D.; Burnworth, M.; Rowan, S.J.; Weder, C. Fluorescent organometallic sensor for the detection of chemical warfare-agent mimics. Angew. Chem. Int. Ed. 2006, 45, 5825–5829. [CrossRef] 13. Sarkar, S.; Mondal, A.; Tiwari, A.K.; Shunmugam, R. Unique emission from norbornene derived terpyridine—A selective chemodosimeter for G-type nerve agent surrogates. Chem. Commun. 2012, 48, 4223–4225. [CrossRef] 14. Ordroneau, L.; Carella, A.; Pohanka, M.; Simonato, J.P. Chromogenic detection of sarin by discolouring decomplexation of a metal coordination complex. Chem. Commun. 2013, 49, 8946–8948. [CrossRef] 15. Maza, W.A.; Vetromile, C.M.; Kim, C.; Xu, X.; Zhang, X.P.; Larsen, R.W. Spectroscopic investigation of the noncovalent association of nerve agent simulant diisopropyl methylphosphonate (DIMP) with zinc (II) porphyrins. J. Phys. Chem. A 2013, 117, 11308–11315. [CrossRef][PubMed] 16. Borba-Bon, A.; Costero, A.M.; Gil, S.; Sancenón, F.; Martinez-Máñez, R. Chromo-ﬂuorogenic BODIPY complexes for selective of V-type nerve agent surrogates. Chem. Commun. 2014, 50, 13289–13291. [CrossRef] [PubMed] 17. Kumar, V.; Raviraju, G.; Rana, H.; Rao, V.K.; Gupta, A.K. Highly selective and sensitive chromogenic detection of nerve agents (sarin, tabun and VX): A multianalyte detection approach. Chem. Commun. 2017, 53, 12954–12957. [CrossRef][PubMed] 18. Sheet, K.S.; Sen, B.; Khatua, S. Organoiridium(III) complexes as luminiscence color swithing probes for selective detection of nerve agent simulant in solution and vapor phase. Inorg. Chem. 2019, 58, 3635–3645. [CrossRef][PubMed] 19. Ishida, R.; Narita, H.; Tonosaki, K. Copper(II)-2,2´-bipyridine-eriochrome cyanine R ternary complex and its application to the spectrophotometric determination of copper(II). Bull. Chem. Soc. Jpn. 1978, 51, 1751–1754. [CrossRef] 20. Dacres, H.; Narayanaswamy, R. Evaluation of cooper(II) eriochrome cyanine R (ECR) complex immobilized in anion exchange membrane as a potential nitric oxide optical sensor. Aust. J. Chem. 2008, 61, 189–196. [CrossRef] 21. Dapson, R.; Horobin, R.W.; Kierman, J. Hematoxylin shortages: Their causes and duration, and other dyes that can replace hemalum in routine hematoxylin and eosin staining. Biotech. Histochem. 2010, 85, 55–63. [CrossRef] 22. Sarsam, L.A.; Bashir, W.A. Spectrophotometric determination of scandium(III) with eriochrome cyanine R and cetylpyridinium chloride—Application to waters and synthetic alloys. J. Raf. Sci. 2009, 20, 48–65. 23. Langmyhr, F.J.; Stumpe, T. Complex formation of iron(III) with eriochrome cyanine R. Anal. Chim. Acta 1965, 32, 535–543. [CrossRef] 24. Majeed, A.; Asma, D.R.N.; Sana-Ullah, M. Spectrophotometric determination of iron with xylenol orange. J. Chem. Soc. Pak. 1996, 18, 197–200. 25. Mizuguchi, H.; Yotsuyanagi, T. Visual threshold detection of trace metal ions using a bi-functional metallochromic reagent. Anal. Sci. 2001, 17, i1687–i1689, Supplement. 26. Barghouthi, Z.; Amereih, S. Spectrophotometric determination of ﬂuoride in drinking water using aluminium complexes of triphenylmethane dyes. Water SA 2012, 38, 543–548. [CrossRef]

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).