A phenothiazine-based colorimetric
chemodosimeter for the rapid detection of cyanide
anions in organic and aqueous media
†
Bhaskar Garg,aLinyin Yan,bTanuja Bisht,cChaoyuan Zhuband Yong-Chien Ling*a
A novel, phenothiazine-based chemodosimeteric probe PCP 1 has been developed and studied as a cyanide selective indicator in organic and aqueous media. Complete colour bleaching was observed due to nucleophilic addition of cyanide to the tricyanovinyl moiety of PCP 1,
which results in the disruption of the extended conjugate and turn-off
the intramolecular charge transfer process.
Introduction
The development of chemosensors and chemodosimeters for anions, an integral part of our biological system, is an area of emerging interest in supramolecular and anion coordination chemistry.1Among various anions, CNis particularly
impor-tant due to its extreme toxicity towards mammals.2The rapid
absorption of CNwithin blood and its binding with Fe3+, an active site of cytochrome c, inhibits cellular respiration in mammalian cells, leading to vomiting, convulsions, loss of consciousness, and eventual death.3Despite this grey side, the industrial use of cyanide salts in gold mining, electroplating, metallurgy, and production of organic chemicals, synthetic bers or resins remains widespread.4 However, the accidental
release of cyanide might lead to very serious problems. Thus a convenient and robust detection of CN is of crucial importance.
To date, considerable efforts have been devoted to develop optical sensors for CN, in which a change in colour or
uorescence intensity is monitored.5Among them, colorimetric
sensors are especially appealing as the signalling events can be detected by naked eye.6Nevertheless, most of the chromogenic
systems for CNsuffer from their limited sensing features only in organic solvents as well as low sensitivity employing high concentration of CN (>1.9 mM), which is not permissible, specically, in drinking water (#1.9 mM) as suggested by World Health Organization (WHO).7 In this context, it is critical to search for a sensor paradigm that combines the operational benets of instrumentation free and cost-effective protocol with the convenience in aqueous solution, whilst retaining high selectivity and sensitivity for rapid CNdetection.
Since itsrst appearance in 1883,810H-phenothiazine (PTZ)
3 has found rising applications as electrophoric sensors in supramolecular assemblies for photo-induced electron transfer (PET),9 electrically conducting charge-transfer composites,10
polymers,11 donor–acceptor arrangements,12 organic
light-emitting diodes (OLEDs),13multifunctional sensors,14and also
as chromophores in dye-sensitized photovoltaic cells.15Despite
this inuential “aura” of PTZ core, the PTZ-based chromogenic systems for anions are relatively scarce.16Furthermore, to the best of our knowledge, PTZ-based cyanide chemosensors or chemodosimeters are still unprecedented. In continuation of our interest in the unswerving recognition of biologically important analytes,17herein, we disclose a simple yet robust and novel phenothiazine-based chemodosimeteric probe, 10-butyl-3-tricyanovinyl-10H-phenothiazine, PCP 1 for the rapid, sensitive and selective detection of cyanide anions in organic and aqueous media.
Results and discussion
The structure and synthesis ofPCP 1 is outlined in Scheme 1. Briey, the reaction of 3 with n-butyl bromide in anhydrous acetone followed by tricyanovinylation of 10-butyl-10H-pheno-thiazine2 with TCNE in anhydrous DMF–THF mixture (1 : 1 v/v) furnishedPCP 1 in moderate yield. The structure and purity of PCP 1 along with 2 and 3-tricyanovinyl-10H-phenothiazine 4‡ aDepartment of Chemistry, National Tsing Hua University, 101, Section 2, Kuang-Fu
Road, Hsinchu, 30013, Taiwan. E-mail: [email protected]; Fax: +886 35727774; Tel: +886 35715131 ext. 33394
b
Department of Applied Chemistry, National Chiao Tung University, 1001 Ta Hsueh Road, Hsinchu 30010, Taiwan. Tel: +886 35712121 ext. 56582
cDepartment of Chemistry, Government Degree College, Champawat, 262523,
Uttarakhand, India
† Electronic supplementary information (ESI) available: Experimental procedures for the synthesis, spectral data, and copies of1H NMR and13C NMR ofPCP 1 and
4; data for UV-vis absorption experiments; theoretical calculation results; and other relevant data. See DOI: 10.1039/c4ra06440b
Cite this: RSC Adv., 2014, 4, 36344
Received 30th June 2014 Accepted 11th August 2014 DOI: 10.1039/c4ra06440b www.rsc.org/advances
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were unambiguously conrmed by1H and13C NMR
spectros-copy (see ESI†). It is worthwhile to mention here that the protection of 10N–H in 3 as well as attachment of tricyanovinyl (TCV) motif to the PTZ core completely switched-off the original blueuorescence of 3, and consequently PCP 1 and 4 appeared as non-uorescent but colorimetric sensors.
In therst step, the anion recognition behaviour of 4 (5.0 105M) towards certain anions (as their tetrabutylammonium salts) was tested in DCM solution. In particular, the absorption spectroscopic titrations of 4 with most basic F, AcO, and H2PO4as well as CNinduced typical spectral shis
attribut-able to the normal N–H-anion hydrogen bonding interactions. Concomitantly, the DCM solution of 4 exhibited a colour change from blue to turquoise blue in the presence of F, AcO, H2PO4, and CNand thus the selectivity of4 towards
partic-ular anion such as CNwas seriously in question (see ESI†). Based on the quantum chemical calculations at the semi empirical level,18it was envisioned that by protecting 10N–H of 3, CN could preferentially attack at the C30-position (charge density¼ 0.011; see ESI†) of the TCV motif in PCP 1. In an attempt to better understand this phenomenon, structural optimization of the structures were carried out by DFT calcu-lations at B3LYP/6-311++G** level.18As demonstrated in Fig. 1
(lower le panel), the optimized structure of PCP 1 has extended p conjugation between the phenyl and TCV groups. Notably, the HOMO ofPCP 1 was delocalized onto the sulphur atom, and the LUMO was delocalized over the TCV group indicating that intramolecular charge transfer (ICT) from sulphur atom to TCV group could occur.
Whereas2 is transparent, PCP 1 bearing a TCV-motif exhibits a blue colour in DCM solution (lmax ¼ 600 nm). Thus, the
expected nucleophilic attack of CNshould result in interrup-tion of p conjugation, which would inuence the UV-vis absorption with apparent loss in colour. The initial evidence for the nucleophilic addition of CN to PCP 1 was assessed by high resolution mass spectrometry in which a peak at m/z 382.1129 corresponding toPCP 1–CNadduct was observed (Fig. S14†). In fact, absorption spectroscopic titrations of PCP 1 with CNresulted in signicant changes in the UV-vis spectra (Fig. 2). In particular, the disappearance of the visible bands (complete bleaching), instead of a shi, pointed out to a
chemical reaction between CN and PCP 1 in a chemo-dosimeter fashion as proposed in Fig. 1.
In order to further evaluate the nature of the reaction of cyanide withPCP 1, we monitored the1H NMR spectral changes produced via the gradual addition of CNin (CD3)2SO at room
temperature. As shown in Fig. 3a, all the aromatic proton signals exhibited an up-eld shi aer addition of 1 equiv. of CN. The striking difference corresponded to the aromatic
Scheme 1 Synthesis of PCP 1 and 4.
Fig. 1 Upper panel: proposed product obtained from the reaction of
CNwith PCP 1; lower panel: calculated HOMO and LUMO
distribu-tion of PCP 1 and its CNadduct.
Fig. 2 UV-vis absorption spectral changes of PCP 1 (5.0 106M)
upon addition of increasing amount of CN(as tetrabutylammonium
salt; 0/ 2 equiv.) in DCM. Inset (left): (a) a solution of PCP 1 (5 mM in
DCM). (b) Addition of 2 equiv. of CNto solution (a). Inset (right):
titration profile of the observed changes at l ¼ 600 nm.
protons (H1; 7.80 and H4; 7.66 ppm) which completely
dis-appeared, whereas two new signals appeared at d 7.35 and 6.96 ppm, respectively. These observations suggest a nucleophilic attack at the C30-position as the likely mechanism for the
interaction betweenPCP 1 and CN. Furthermore, the absence of a signal at3.5–3.9 ppm, corresponding to the C–H proton of the malononitrile group, indicated possible formation of a stabilized anionic species.
Fig. 3 (a) Partial1H NMR (600 MHz, (CD3)2SO) spectral changes seen upon the addition of 0–1.2 equiv. of CNto PCP 1 (10.0 mM). In red: signals
disappearing. In blue: signals appearing during titration; (b) selected region of1H NMR (600 MHz, CD3CN) of PCP 1 at room temperature (RT) and
PCP 1–CNadduct at temperatures ranging from RT (295 K) to40C (233 K). Red stars: signals due to N-butyl chain of PCP 1. Blue stars: signals
due to N-butyl chains of tetrabutylammonium cyanide. S denotes solvent.
Occasionally, the C–H proton attached to the dicyano carbon is not observed leading to misinterpretation of the obtained results. Taking this into account, the proposed reaction pathway for CN sensing was unambiguously conrmed by recording1H NMR spectra ofPCP 1–CNadduct in CD
3CN at
temperatures ranging from 283 K to 233 K and comparing with the1H NMR spectra ofPCP 1–CNadduct at room temperature
(295 K). As can be seen in Fig. 3b, most resonances due to the N-terminated butyl chain protons of both thePCP 1–CNadduct and tetrabutylammonium cyanide experienced a noticeable up-eld shiing upon successively decreasing the temperature from 295 K to 233 K. Nevertheless, no new proton signal was recognized during the course of low temperature NMR study.
Based on these observations, structural optimization of the structure for thePCP 1–CNadduct was carried out (Fig. 1). In sharp contrast toPCP 1, the LUMO distribution on the vinyl group was signicantly reduced and localized to only the phenyl group of PTZ core. Therefore, the nucleophilic addition of CN to the TCV group inPCP 1 prevents ICT and results in complete bleaching of the colour.
To evaluate the cyanide selective nature ofPCP 1, absorption spectral changes caused by the addition of other anions including F, Cl, Br, I, HSO4, NO3, H2PO4 and AcO
were studied. Specically, 10 equiv. of each anion were added to a DCM solution ofPCP 1 (5 mM) and incubated for 5 min at 25 C, before being subjected to spectral analysis. Most of these anions did not cause any signicant changes in the UV-vis absorption and the colour of the solution remained intact. However, in addition to cyanide,PCP 1 also exhibited UV-vis absorption changes (though weak) aer addition of F,
indi-cating that Facts as a strong competitor of CNunder these conditions (Fig. 4).
To understand the interaction mode betweenPCP 1 and F, the additional 1H NMR titration experiment was carried out
(Fig. S16†). Surprisingly, unlike CN, the addition of Fto the
(CD3)2SO solution ofPCP 1 elicited only negligible changes in
the1H NMR spectra. In particular, the aromatic protons (H1and
H4) inPCP 1 did not experience any possible shielding over the
course of Ftitration. Nevertheless, a considerable decrease in the intensity of H1and H4was realized, and accompanied by
some splitting in the remaining aromatic protons in PCP 1. These results suggest that Fdoes not react with PCP 1 in a scientic manner but possibly has some degradation effect on the same.
In order to verify the competing assay of F, time-dependent absorption spectral changes were monitored in the presence of Fand CN(5 equiv.) in DCM at l ¼ 600 nm. Aer the addition of F, the absorbance intensity decreased only by 50% and reached a podium within 10 min. On the contrary, aer the addition of CN, a remarkable reduction (>99%) in the intensity of the 600 nm absorption band could be observed within 60 s of mixing demonstrating the high reactivity of CN over F (Fig. S17†).
Although CNcaused profound spectral changes than F, the latter also displayed colour bleaching in DCM and thus chromo (visual) selectivity ofPCP 1 towards CN was still in question. It is well known that the nucleophilicity/basicity of anions, in particular, Fis greatly decreased in water due to its high solvation effect.19
Taking this into account, we retested the CNselectivity of PCP 1 in aqueous solution adopting a surfactant-assisted protocol.20 Although PCP 1 has poor solubility in water yet readily dissolves in aqueous solution containing the neutral surfactant, Triton X-100. To test the cyanide selectivity in aqueous medium, PCP 1 in THF (100 mL, 2 105 M)§ was added to water mixture containing Triton X-100 (1 102M) and the resulting solutions were used to monitor the UV-vis spectral changes before and aer the addition of Fand CN.
Aer 10 min of incubation, only the solution that included CN
exhibited70% reduction in absorption intensity (Fig. 5). This observation is sharply in contrast to what observed in DCM solution and can be attributed to the cyanide induced solvation process. In addition, relatively lower hydration energy for CN
Fig. 4 (a) UV-vis spectral changes of PCP 1 (5.0 106M) and (b)
corresponding colour responses seen upon the addition of 10 equiv. of various anions (as their tetrabutylammonium salts) in DCM.
Fig. 5 Changes in the visible band (l ¼ 600 nm) of PCP 1 (2 105M)
in water with Triton X-100 (1 102M) in the presence of 5 equiv. of
Fand CN. Inset: colour changes of PCP 1 (A; 1mM) in Triton
X-100-water solution in the presence of 1mM (B), 1.5 mM (C), 2.5 mM (D), and 5
mM (E) of NaCN after 10 min of incubation.
(DHhyd¼ 67 kJ mol1) than that of F(DHhyd¼ 505 kJ mol1)
further explains the CNselectivity in aqueous environment.21 Colorimetric detection of micromolar concentrations of inorganic CN(NaCN) and F(NaF) was then evaluated using PCP 1 in surfactant-assisted water solution (Inset: Fig. 5; for F,
see Fig. S18†). In particular, PCP 1 was found to exhibit a successful response, manifested in signicant bleaching within 1.5mM of cyanide concentration. As shown in Fig. S19,† A good linear relationship (R2 ¼ 0.9875) between the absorption intensity and the CNconcentration could be obtained. The detection limit was then calculated to be 1.56 106 M according to the following equation: detection limit ¼ 3S/r, where S is the standard deviation of blank measurements, r is the slope between intensity versus CN concentration. This result indicates that the colorimetric detection limit byPCP 1 is in good agreement with WHO guidelines (1.9mM) for cyanide toxicity.
Conclusions
In summary, we have successfully designed and demonstrated that the phenothiazine-based chemodosimeteric probe,PCP 1, can be synthesized and such systems, as currently produced, are selective for CN, especially, in aqueous media. Although several colorimetric probes for CN detection have been reported, most utilize organic solvents as the major detection medium usually containing a very low percentage of water (#20% by volume). This is one of the very few colorimetric probes described for CNdetection in surfactant-assisted pure water. Consequently,PCP 1 appears to be a practical system for colorimetric detection of CN in aqueous media. Design and synthesis of more sensitive PTZ-based chemodosimeters or chemosensors for diverse sensing applications including cyanide anion are currently in progress.
The authors are thankful to National Tsing Hua University (102N1807E1) and the Ministry of Science and Technology (NSC101-2113-M-007-006-MY3) of Taiwan for nancial assistance.
Notes and references
‡ The synthesis of 4 has been though previously reported, the NMR structural characterization as well as anion recognition properties of4 are unprecedented (for details; see ESI†).
§ The optimized concentration, approaching nearly identical absorbance of PCP 1 as was in DCM (5 106M).
1 (a) R. Mart´ınez-M´a˜nez and F. Sancen´on, Chem. Rev., 2003, 103, 4419; (b) C. Suksai and T. Tuntulani, Chem. Soc. Rev., 2003,32, 192; (c) B. Garg, T. Bisht and S. M. S. Chauhan, New J. Chem., 2010, 34, 1251–1254; (d) B. Garg, T. Bisht and S. M. S. Chauhan, Sens. Actuators, B, 2012,168, 318–328. 2 (a) S. I. Baskin and T. G. Brewer, in Medical Aspects of Chemical and Biological Warfare, ed. F. Sidell, E. T. Takafuji and D. R. Franz, TMM Publication, Washington DC, 1997, ch. 10, p. 271; (b) K. W. Kulig, Cyanide Toxicity, U. S. Department of Health and Human Services, Atlanta, 1991.
3 (a) S. I. Baskin, J. B. Kelly, B. I. Maliner, G. A. Rockwood and C. K. Zoltani, in Medical Aspects of Chemical Warfare, ed. D. T. Shirley, TMM Publication, Washington DC, 2008, ch. 11, p. 331; (b) J. L. Way, Annu. Rev. Pharmacol. Toxicol., 1984,24, 451.
4 (a) R. Koenig, Science, 2000,287, 1737; (b) G. C. Miller and C. A. Pritsos, Cyanide: Soc., Ind. Econ. Aspects, Proc. Symp. Annu. Meet. TMS, 2001, 73.
5 (a) Z. Xu, X. Chen, H. N. Kim and J. Yoon, Chem. Soc. Rev., 2010,39, 127; For recent reviews on cyanide sensing as a part-topic see: ; (b) D. G. Cho and J. L. Sessler, Chem. Soc. Rev., 2009,38, 1647; (c) M. E. Moragues, R. Mart´ınez-M´a˜nez and F. Sancen´on, Chem. Soc. Rev., 2011,40, 2593; (d) J. Du, M. Hu, J. Fan and X. Peng, Chem. Soc. Rev., 2012,41, 4511; (e) K. Kaur, R. Saini, A. Kumar, V. Luxami, N. Kaur, P. Singh and S. Kumar, Coord. Chem. Rev., 2012,256, 1992; (f) Y. Yang, Q. Zhao, W. Feng and F. Li, Chem. Rev., 2013, 113, 192; (g) P. A. Gale, N. Busschaert, C. J. E. Haynes, L. E. Karagiannidis and I. L. Kirby, Chem. Soc. Rev., 2014, 43, 205; (h) L. E. Santos-Figueroa, M. E. Moragues, E. Climent, A. Agostini, R. Mart´ınez-M´a˜nez and F. Sancen´on, Chem. Soc. Rev., 2013,42, 3489.
6 (a) Y.-K. Yang and J. Tae, Org. Lett., 2006,8, 5721; (b) X. Lou, J. Qin and Z. Li, Analyst, 2009, 134, 2071; (c) S. Basurto, D. Miguel, D. Moreno, A. G. Neo, R. Quesada and T. Torroba, Org. Biomol. Chem., 2010,8, 552; (d) N. Kumari, S. Jha and S. Bhattacharya, J. Org. Chem., 2011,76, 8215; (e) C. M¨annel-Crois´e and F. Zelder, Anal. Methods, 2012,4, 2632. 7 Guidelines for Drinking-Water Quality; World Health
Organization, Geneva, 1996.
8 A. Bernthsen and B. Dent, Ber. Dtsch. Chem. Ges., 1883,16, 2996.
9 (a) A. M. Brun, A. Harriman, V. Heitz and J.-P. Sauvage, J. Am. Chem. Soc., 1991,113, 8657; (b) J. Strauss and J. Daub, Adv. Mater., 2002,14, 1652.
10 (a) H. Spreitzer and J. Daub, Chem.–Eur. J., 1996, 2, 1150; (b) A. Knorr and J. Daub, Angew. Chem., Int. Ed., 1995,34, 2664. 11 (a) F. Fungo, S. A. Jenekhe and A. J. Bard, Chem. Mater., 2003, 15, 1264; (b) M. Y. Jo, S. S. Park and J. H. Kim, Syn. Met., 2012, 162, 70.
12 (a) S. S. Park, Y. S. Won, Y. C. Choi and J. H. Kim, Energy Fuels, 2009, 23, 3732; (b) H.-H. Lin, S.-Y. Su and C.-C. Chang, Org. Biomol. Chem., 2009,7, 2036.
13 (a) R. Y. Lai, X. Kong, S. A. Jenekhe and A. Bard, J. Am. Chem. Soc., 2003, 125, 12631; (b) N. S. Cho, J. H. Park, S. K. Lee, J. Lee, H. K. Shim, M. J. Park, D. H. Hwang and B. J. Jung, Macromolecules, 2006, 39, 177; (c) G. W. Kim, M. J. Cho, Y. J. Yu, Z. H. Kim, J. I. Jin, D. Y. Kim and D. H. Choi, Chem. Mater., 2007,19, 42.
14 (a) M. Hauck, J. Schonhaber, A. J. Zucchero, K. I. Hardcastle, T. J. J. Muller and U. H. F. Bunz, J. Org. Chem., 2007,72, 6714; (b) G. Ajaykumar, K. Sreenath and K. R. Gopidas, Dalton Trans., 2009, 1180; (c) S. Y. Su, H.-H. Lin and C.-C. Chang, J. Mater. Chem., 2010, 20, 8653; (d) J. Wu, H. Guo, X. Zhang, T. D. James and J. Zhao, Chem.–Eur. J., 2011, 17, 7632; (e) J. Weng, Q. Mei, B. Zhang, Y. Jiang, B. Tong, Q. Fan, Q. Ling and W. Huang, Analyst, 2013,138, 6607.
15 (a) H. Tian, X. Yang, R. Chen, Y. Pan, L. Li, A. Hagfeldt and L. Sun, Chem. Commun., 2007, 3741; (b) C. Chen, J.-Y. Liao, Z. Chi, B. Xu, X. Zhang, D.-B. Kuang, Y. Zhang, S. Liu and J. Xu, J. Mater. Chem., 2012,22, 8994.
16 (a) F. Han and J. Zhao, Helv. Chim. Acta, 2008,91, 635; (b) A. Kormos, I. M´ocz´ar, A. Sveiczer, P. Baranyai, L. P´ark´anyi, K. T´oth and P. Huszthy, Tetrahedron, 2012, 68, 7063; (c) A. Kormos, I. M´ocz´ar, D. P´al, P. Baranyai, T. Holczbauer, A. Pall´o, K. T´oth and P. Huszthy, Tetrahedron, 2013,69, 8142. 17 (a) B. Garg and Y.-C. Ling, RSC Adv., 2013, 3, 10150; (b) B. Garg, S.-L. Lei, S.-C. Liu, T. Bisht, J.-Y. Liu and Y.-C. Ling, Anal. Chim. Acta, 2012,757, 48.
18 M. J. Frisch, G. W. Trucks and H. B. Schlegel, et al., Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford, CT, 2009.
19 (a) C. B. Black, B. Andrioletti, A. C. Try, C. Ruiperez and J. L. Sessler, J. Am. Chem. Soc., 1999, 121, 10438; (b) Y.-D. Lin, Y.-S. Pen, W. Su, K.-L. Liau, Y.-S. Wen, C.-H. Tu, C.-H. Sun and T. J. Chow, Chem.–Asian J., 2012, 7, 2864– 2871; (c) M. Schmittel and S. Qinghai, Chem. Commun., 2012,48, 2707–2709.
20 (a) K. Niikura and E. V. Anslyn, J. Org. Chem., 2003,68, 10156; (b) T. ´Abalos, S. Royo, R. Mart´ınez-M´a˜nez, F. Sancen´on, J. Soto, A. M. Costero, S. Gil and M. Parra, New J. Chem., 2009,33, 1641.
21 S. Saha, A. Ghosh, P. Mahato, S. Mishra, S. K. Mishra, E. Suresh, S. Das and A. Das, Org. Lett., 2010,12, 3406.
