Benzoquinone based chemodosimeters for selective and sensitive colorimetric and turn-on fluorescent sensing of cyanide in water

Accepted Manuscript Title: Benzoquinone based chemodosimeters for selective and sensitive colorimetric and turn-on fluorescent sensing of cyanide in water Author: Palanisamy Jayasudha Ramalingam Manivannan Kuppanagounder P. Elango PII: DOI: Reference:

S0925-4005(17)30928-0 http://dx.doi.org/doi:10.1016/j.snb.2017.05.105 SNB 22389

To appear in:

Sensors and Actuators B

Received date: Revised date: Accepted date:

15-4-2017 17-5-2017 17-5-2017

Please cite this article as: P. Jayasudha, R. Manivannan, K.P. Elango, Benzoquinone based chemodosimeters for selective and sensitive colorimetric and turn-on fluorescent sensing of cyanide in water, Sensors and Actuators B: Chemical (2017), http://dx.doi.org/10.1016/j.snb.2017.05.105 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Benzoquinone based chemodosimeters for selective and sensitive colorimetric and turn-on fluorescent sensing of cyanide in water

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Palanisamy Jayasudha, Ramalingam Manivannan and Kuppanagounder P. Elango*

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Highlights Five chemodosimeters with different substituents were designed and synthesized.

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They selectively sense cyanide in water colorimetrically with turn-on fluorescence.

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The mechanism of sensing involves nucleophilic addition of cyanide to C=C bond.

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They exhibited structure-activity relationship with Hammett substituent constants.

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Benzoquinone based chemodosimeters for selective and sensitive colorimetric and turn-on fluorescent sensing of cyanide in water Palanisamy Jayasudha, Ramalingam Manivannan and Kuppanagounder P. Elango*

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Department of Chemistry, Gandhigram Rural Institute- Deemed University, Gandhigram624302, India.

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ABSTRACT

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Dibromobenzoquinone-indole ensembles containing different substituents (OMe, Me, H, Br, and NO2) have been designed, synthesized and characterized using spectral techniques.

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These chemodosimeters selectively sense cyanide ion colorimetrically with turn-on fluorescence in aqueous HEPES buffer. Absorption and emission spectral studies suggest that the interaction

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between the receptors and cyanide is strong (binding constant in the order of 104 M-1) with 1:1 stoichiometry. The detection limit for these receptors to sense cyanide is found to be in the nano

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C NMR titration results indicate that the mechanism of sensing of

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drinking water. 1H and

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molar range which is far below the permissible limit recommended by WHO for cyanide ion in

cyanide by these receptors is through neucleophilic addition of cyanide to the C=C bond of the indole ring. The electro-reduction potentials for the quinone moiety before and after the addition of cyanide substantiate the proposed mechanism. Mulliken charges computed, using DFT method, suggest that these receptors possess an electropositive C-atom for the addition reaction to occur, while such charge polarization is not there in similar compounds containing benzoquinone or naphthoquinone. The effect of substituents on the λICT, binding constant and δNH of indole has been explained using Hammett’s substituents constants (σp). Keywords: Cyanide; Sensor; Colorimetry; Quinone; Chemodosimeter * Corresponding author. Tel.: +91 451 245 2371; Fax: +91 451 2454466

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E-mail address: [email protected] (Dr. K.P. Elango)

1.

Introduction

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In recent years, the development of new chemical sensors for the detection of anions has received more interest due to their biological, environmental and chemical applications [1-3].

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Among the various hazardous anions, cyanide is extremely lethal to living thing because it binds

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strongly with cytochrome c oxidase, thus inhibiting the mitochondrial electron transport chain which in turn leads to loss of consciousness, convulsions, vomiting and at last death [4, 5]. The

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average lethal dose of cyanide ion is 0.5-3.5 mg/kg of body weight [6]. On the other hand cyanide is useful in numerous industrial processes such as gold and silver extraction, tanning,

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metallurgy, plastic manufacturing, case hardening of metals etc. [7-9]. The World Health Organization (WHO) has set the maximum tolerable concentration level of cyanide in drinking

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water as 1.9 µM [10].

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Hence, the rational design and synthesis of effective chemosensors to recognize cyanide ion selectively is a significant part of supramolecular chemistry. A variety of sensors have been developed for the detection of cyanide by different kinds of sensing methods [11-15]. Out of which colorimetric approach would be of great interest as it allows us to see the detection visually without the use of expensive instruments. The chemosensors designed and reported so far, to detect cyanide ion, works through either of various modes like complex formation with transition metals, hydrogen bonding interactions, displacement approach, nucleophilic addition reactions etc. [16-23]. Among this, chemodosimeters are molecular probes used to attain the detection of analyte with irreversible chemical process and reveals high selectivity by minimized interference of other anions [24-26]. Further, as it works via permanent chemical reaction, they can do so in water medium, which could be the most desired outcome of such investigations. On

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the other hand, for sensors which work through H-bonding interaction with the analyte, the high hydration energy of anions prevents them from accommodating more amount of water in the sensing medium.

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During recent past, we are in the process of designing quinone based receptors, possessing two different reaction sites viz. H-bond donor N-H moiety and a C=C bond

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susceptible to nucleophilic addition reaction, for selective sensing of cyanide ion colorimetrically

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in aqueous solutions. Chemodosimeters based on 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-indole ensembles (I), possessing electron donating (R = OMe and Me) and electron

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withdrawing (R = NO2 and Br) substituents in addition to R = H, have been shown to colorimetrically sense cyanide ion selectively in H2O:acetonitrile (80:20% v/v) medium through

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nucleophilic addition of cyanide to C=C bond of indole ring (Fig. 1) [27]. Very recently, naphthoquinone-indole based receptors (II) possessing the same set of substituents in the indole

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ring have been reported by us, which sense cyanide ions selectively in H2O:DMF (50:50% v/v)

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medium through H-bond formation between N-H and cyanide ion along with a striking colour change from yellow to bluish green [28]. In both the cases a structure-reactivity correlation was observed on the effect of substituents on the intensity of binding of cyanide with the receptors. Also, in these receptors existence of intramolecular charge transfer (ICT) transition from indole N-H moiety to the electron deficient quinone through the C=C bond makes the molecule to absorb visible light and hence highly coloured. In the case of I, nucleophilic addition of cyanide to this C=C bond switched-off the ICT transition and in II H-bonding enhanced the intensity of ICT transition, both of which lead to striking colour change that could be seen easily by naked eye.

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Furthermore, the results of these studies indicated that change of the nature of quinone have a great influence on the electropositive character of the C-atom (α to N-H), which determines whether cyanide sensing will occur via nucleophilic addition or via H-bond

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formation. Having been satisfied with the design and performance of these receptors in aqueous solutions, we thought that similar design strategy could also be extended to simple benzoquinone

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system also (III), with an aim to investigate their anion sensing behaviour. However, density

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functional theory (DFT) based calculations have shown that in III, the electron withdrawing nature of the quinone moiety is not strong enough to make the C-atom more electropositive,

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where the nucleophilic addition of cyanide ion is going to occur. Also, review of literature has revealed that preparation of III is rather difficult and most of the attempts to synthesize III

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yielded only diindolylbenzoquinone [29,30]. Further, the theoretical calculations have shown that 2,5-dibromo-1,4-benzoquinone based receptors would serve the purpose. Hence, 2,5-

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dibromo-1,4-benzoquinone/indole ensembles (R) containing five different substituents have been

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synthesized and screened for their ability to sense anions. Interestingly these receptors sense cyanide ions selectively and sensitively with a striking colour change and also with turn-on fluorescence in water. The cyanide ion sensing properties of these receptors are explored using UV-Vis, fluorescence and 1H and 13C NMR spectral studies and electrochemical and theoretical studies. 2.

Experimental section

2.1

Chemicals and apparatus

All the reagents for the synthesis of the receptors were obtained commercially and were used without further purification. Spectroscopic grade solvents were used as received. Doubly distilled water was used throughout the work and the second distillation was carried out using

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alkaline permanganate. UV-Vis spectral studies were carried out on a double beam spectrophotometer. Steady state fluorescence spectra were obtained on a spectrofluorimeter. The excitation and emission slit width (5 nm) and the scan rate (250 mVs-1) were kept constant for all

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of the experiments. Nuclear magnetic resonance spectra were recorded in DMSO-d6 (400 or 600 MHz). The 1H NMR spectral data is expressed in the form: Chemical shift in units of ppm

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(normalized integration, multiplicity, and the value of J in Hz). Electro spray ion mass spectra

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(m/z) were recorded using LC/MSD TRAP XCT Plus (1200 Agilent). The differential pulse voltammetric (DPV) experiments, of 1 mmol solutions of the compounds, were carried out using

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GC as working, Pt wire as reference and Ag wire as auxiliary electrodes in acetonitrile containing 0.1 M tetrabutylammonium perchlorate as supporting electrolyte at a scan rate of 100

Synthesis and characterization of intermediates The

intermediates

2,5-dibromo-1,4-dimethoxybenzene

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2.2

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mVs-1.

(1)

and

2,5-dibromo-1,4-

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benzoquinone (2) were prepared from commercially available 1,4-dimethoxybenzene as reported earlier [31]. The intermediates 1 and 2 were characterized using 1H NMR and LC-MS spectral techniques. The results obtained are: (1): Pale white solid (18.3 g, yield 85%). δH (400 MHz; DMSO-d6; Me4Si/ppm): 3.62-3.99 (3H, m), 7.35 (1H, s) (Fig S1). LC-MS (ESI-APCI) m/z: cacld. for C8H8Br2O2, 295.96, found, 296.8 [M+H]+ (Fig S2). (2): Yellow solid (3.8 g, yield 84%). δH (400 MHz; DMSO-d6; Me4Si/ppm): 7.76 (2H, s) (Fig S3). LC-MS (ESI-APCI) m/z: cacld. for C6H2Br2O2, 265.89, found, 267.2 [M+H]+ (Fig S4). The spectral results matched well with those reported in literature.

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2.3

General procedure for synthesis of receptors (R1-R5) To a solution of 2 (1 g, 3.76 mmol) in THF (10 mL), corresponding indole (3.76 mmol)

and few drops of Con. HCl were added and stirred for 5 h. After that the reaction mixture was

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concentrated under vacuum and the residue obtained was partitioned between water and ethyl acetate. The organic layer thus obtained was concentrated to get the crude product, which was

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then reacted with DDQ (3.76 mmol) in DCM (5 mL) and stirred at room temperature for 2 h. The

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reaction mixture was concentrated and the residue obtained was partitioned between water and ethyl acetate. The organic layer was concentrated and then purified by column chromatography

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to yield the pure product (Scheme 1). The receptors R1-R5 were characterized using 1H and 13C NMR and LC-MS spectral techniques. The results obtained are:

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Receptor R1: Dark blue solid (1.05 g, yield 68%). δH (600 MHz; DMSO-d6; Me4Si): 3.72 (s, 3H), 6.79-6.81 (dd, 1H, J=2.4 Hz, J=9 Hz), 7.21 (s, 1H), 7.35-7.36 (d, 1H, J=9 Hz), 7.57-7.58 (d,

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1H, J=2.4 Hz), 7.80 (s, 1H), 11.69 (s, 1H) (Fig. S5). δC (150 MHz; DMSO-d6; Me4Si): 55.84,

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104.15, 108.72, 112.16, 113.14, 126.20, 131.30, 131.46, 137.01, 137.59, 137.69, 143.35, 154.22, 177.23, 178.42 (Fig. S6). LC-MS (ESI-APCI) m/z: Calcd. for C15H9Br2NO3: 411.04; Found: 412.10 [M+H]+ (Fig. S7).

Receptor R2: Dark blue solid (0.98 g, yield 66%). δH (600 MHz; DMSO-d6; Me4Si): 2.37 (s, 3H), 6.98-6.99 (d, 1H, J=7.8 Hz), 7.13 (s, 1H), 7.34-7.36 (d, 1H, J=8.4 Hz), 7.56-7.57 (d, 1H, J=3 Hz), 7.80 (s, 1H), 11.70 (s, 1H) (Fig. S8). δC (150 MHz; DMSO-d6; Me4Si): 21.82, 108.16, 112.24, 121.37, 123.74, 125.87, 128. 79, 130.57, 131.85, 134.67, 136.95, 137.63, 142.66, 177.15, 178.43 (Fig. S9). LC-MS (ESI-APCI) m/z: Calcd. for C15H9Br2NO2: 395.05; Found: 393.90 [MH]+ (Fig. S10).

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Receptor R3: Blue solid (1.12 g, yield 78%). δH (600 MHz; DMSO-d6; Me4Si): 7.06-7.09 (t, 1H, J=7.8 Hz), 7.15-7.17 (t, 1H, J=7.8 Hz), 7.34-7.36 (d, 1H, J=7.8 Hz), 7.46-7.48 (d, 1H, J=7.8 Hz), 7.64 (s, 1H), 7.81 (s, 1H), 11.82 (s, 1H) (Fig. S11). δC (150 MHz; DMSO-d6; Me4Si): 108.58,

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112.54, 120.14, 121.77, 122.14, 125.65, 130.57, 136.31, 137.62, 142.55, 177.12, 178.43 (Fig. S12). LC-MS (ESI-APCI) m/z: Calcd. for C14H7Br2NO2: 381.02; Found: 382.20 [M+H]+ (Fig.

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S13).

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Receptor R4: Violet solid (0.91 g, yield 53%). δH (600 MHz; DMSO-d6; Me4Si): 7.26-7.28 (dd, 1H, J=1.8 Hz, J=8.4 Hz), 7.43-7.45 (d, 1H, J=8.4 Hz), 7.58 (s, 1H), 7.58 -7.59 (d, 1H, J=1.8 Hz),

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7.81 (s, 1H), 11.95 (s, 1H) (Fig. S14). δC (150 MHz; DMSO-d6; Me4Si): 108.28, 112.83, 114.49, 123.88, 124.66, 127.60, 131.37, 133.19, 135.03, 137.69, 139.89, 143.51, 176.87, 178.43 (Fig.

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S15). LC-MS (ESI-APCI) m/z: Calcd. for C14H6Br3NO2: 459.91; Found: 458.80 [M-H]+ (Fig. S16).

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Receptor R5: Violet solid (0.97 g, yield 60%). δH (600 MHz; DMSO-d6; Me4Si): 7.60 (s, 1H)

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7.66-7.67 (d, 1H, J=9.0 Hz), 7.85 (s, 1H), 8.05-8.07 (dd, 1H, J=2.4 Hz, J=9.0 Hz), 8.46-8.47 (d, 1H, J=2.4 Hz), 12.40 (s, 1H) (Fig. S17). δC (150 MHz; DMSO-d6; Me4Si): 108.30, 110.91, 112.07, 123.88, 126.01, 128.97, 130.71, 132.15, 138.75, 139.44, 145.57, 148.86, 177.74, 178.16 (Fig. S18). LC-MS (ESI-APCI) m/z: Calcd. for C14H6Br2N2O4: 426.02; Found: 425.30 [M-H]+ (Fig. S19). 3.

Results and discussions

Five new dibromobenzoquinone-indole ensembles possessing different substituents (OMe, Me, H, Br and NO2) have been synthesized (Scheme 1) and characterized using 1H and 13

C NMR and LC-MS spectral techniques. The stock solutions of these receptors were prepared

in water with the addition of 3-4 drops of acetonitrile (<0.5%). The anion sensing properties of

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these receptors R1-R5 were screened in aq. HEPES buffer (pH 7.26) using different spectral (UV-Vis, fluorescence, 1H and 13C NMR), electrochemical and theoretical techniques.

O

O

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O

Br Br 2

CAN Br O

ACN/H 2 O

Br O

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AcOH O

Br

2

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1

R

N H

O

R

Br

Br O

NH

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Where R1 = OMe R2 = Me R3 = H R4 = Br R5 = NO2

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(i)THF, RT 5 h (ii) DDQ, DCM RT, 2 h

3.1

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Scheme 1. Synthesis of receptors R1-R5.

Visual detection

Colorimetric receptor is a well-defined system where the sensing response can be easily and visually identified. The change in colour of the receptors R1-R5 (2.5x10-4 M) was visually observed with the addition of various anions such as F-, Cl-, Br-, I-, CN-, NO3-, OAc-, H2PO4-, NO2-, CO32-, S2- and PO43- in aq. HEPES buffer. The solutions of the receptors R1-R5 resulted in an instantaneous colour change from blue to yellow with CN- ion (Fig. 2, Fig. S20) and no change in colour were observed with the addition of all other chosen anions. This observation indicated that the receptors are highly selective towards cyanide ion. As a representative case, the color of the receptor R3 at different pH values (pH 2-12) before and after the addition of one

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equivalent of cyanide ion was also inspected. As evidenced from Figure S21, the receptor exhibited similar color change in neutral and basic media. 3.2

UV-Vis spectral studies

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The selectivity shown by these receptors towards cyanide ion in the visible detection experiment was further confirmed by UV-Vis spectral studies. The UV-Vis spectra of these

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receptors (6.25x10-5 M) in the absence and presence of the chosen anions were recorded in aq.

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HEPES buffer. The absorption spectra of the free receptors exhibited an intense band at 559, 553, 549, 530 and 504 nm for R1 (R = OMe); R2 (R = Me); R3 (R = H); R4 (R = Br) and R5 (R

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= NO2), respectively (Fig. 3). This band corresponds to the intramolecular charge transfer (ICT) transition from indole N-H moiety to the electron deficient quinone via the C=C bond [27, 28].

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Further, the position of the band was found to depend on the nature of the substituent. The

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receptor with electron releasing substituents (R1 and R2) exhibited the ICT transition at

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relatively higher wavelengths when compared to the unsubstituted compound (R3). While in the case of the receptors with electron withdrawing substituents (R4 and R5) the ICT transition occurred at relatively lower wavelengths than that of R3. As a result of this difference in the energy requirement for the ICT transition to occur, the colour of the free receptors themselves are different (Fig. 3). This structural effect on the position of the ICT band has been explained using the Hammett’s substituent constant σp [32]. The correlation between the λICT values and σp obtained is shown in Figure S22. The good correlation (r 0.99) showed that the electronic effect of the substituents greatly influences the energy requirement for ICT transition. As expected, there observed negative slope of the plot indicated that increase in the electron releasing nature of the substituent makes the ICT transition energetically easier.

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As a representative case, UV-Vis spectra of R3 (6.25x10-5 M) were recorded with the addition of one equivalent of various anions such as CN−, Cl−, Br−, I−, NO3−, H2PO4−, AcO−, F−, NO2−, S2−, CO32− and PO43− (Fig. S23). As shown in the figure, the ICT transition band of the

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receptor shifted to lower wavelength with the addition of cyanide ion alone. Addition of all other chosen anions did not produce any change in the position and intensity of the band indicating

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high selectivity of receptor towards cyanide ion. As a representative case, the absorption spectra

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of R3 were also recorded in the presence of other competitive anions (Fig. S24). The results indicated that the absorbance intensity of the receptor-cyanide ion system showed no appreciable

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change in the presence of other anions. This strongly suggested that the receptors are highly selective towards fluoride ion.

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The UV-Vis spectral titration of R1-R5 was carried out with the incremental addition of

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cyanide ion in aq. HEPES buffer and the spectra thus obtained are depicted in Figures 4 and S25-

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S28. As evidenced from the figure 4, upon incremental addition of cyanide ion to R3 the absorbance of the band at 549 nm gradually decreased and that of a new peak at a lower wavelength (401 nm) increased concomitantly with a clear isosbestic point at 494 nm. This phenomenon results in an instantaneous colour change, which could be seen visually. Similar spectral changes were observed for all other receptors also and the observed blue shift accompanied with a well-defined isosbestic point indicated a clean transformation to a new species. The observed blue shift is presumably due to the switch-off of the ICT transition by nucleophilic addition of cyanide on to the C=C bond in indole moiety [27]. The stoichiometry of the interaction of the receptors R1-R5 with cyanide ion was determined by Job’s continuous variation method (Fig. S29) [33]. In all the cases, Job’s curve with a maximum at mole fraction of 0.5 indicated 1:1 stoichiometry. The association constant

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(Ka) for the receptor-CN- ion interaction was calculated from the linear (r>0.99) Scott plots [34] and are collected in Table 1. The observed magnitude of the Ka valued suggested the existence of a fairly strong association between the receptors and cyanide ions. Fluorescence spectral studies

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3.3

The interaction between the receptors and cyanide ion was also investigated by

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fluorescence spectral titration experiment in aq. HEPES buffer and the results obtained are

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shown in Figures 5 and S30-S33. As seen from the figure 5, the emission peak of R3 at 424 nm dramatically enhanced with incremental addition of cyanide ion. All the other receptors also

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showed similar fluorescence enhancement with the addition of cyanide ion. From the fluorescence data, the binding constants (K) were calculated using Benesi-Hilderbrand equation

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[35] and the values obtained are collected in Table 2. It is evident from the results that the magnitude of the binding constants depends upon the nature of the substituent present in the

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indole moiety. A plot of K versus Hammett’s σp was found to be fairly linear (r 0.95) with

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positive slope (Fig. 6). The positive slope indicated that the binding constants in the case of electron withdrawing substituents (R4 and R5) are relatively higher than that of unsubstituted receptor (R3) while in the case of electron releasing substituents (R1 and R2) the binding constant values are relatively lesser than that of R3. This is due to the fact that electron withdrawing substituents would reduce the electron density on the N-atom (N-H) and thereby decreased the intensity of ICT transition (as observed in the electronic spectral studies). Such a relatively less intense ICT transition through the C=C bond would polarize the bond to a larger extent (due to the presence of electron withdrawing quinone at one end) and consequently makes the nucleophilic addition of cyanide relatively easier, when compared to the unsubstituted

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receptor R3 (where R = H), as shown below. The reverse is true in the case of electron donating substituents when compared to R3.

Electron withdrawing

O

R

Br

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Strong electron withdrawing

Br O

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NH

more polarized

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Less electron density and poor electron donor in ICT

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The turn-on fluorescence of the receptors upon addition of cyanide ion is well supported by the increase in quantum yields (calculated using quinine sulfate as standard) of the receptors

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after the addition of cyanide ion (Table 2, Fig. S34-S44). The detection limits of the receptors R1-R5 for cyanide ion was determined using the fluorescence spectral data at S/N=3 [36] and

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the values thus obtained are also collected in table 2. The results indicated that these receptors

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could detect cyanide ion in nano molar level which is well below the WHO standard for cyanide ion in drinking water (1.9 µM). Also, the detection limits observed in the present cases are comparable and even lower than that of other chemodosimeters reported in literature (Table S1). 3.4

NMR spectral studies

The proposed mechanism of cyanide sensing by these receptors was probed using 1H and 13

C NMR titration studies in DMSO-d6. The 1H NMR spectra of the receptors R1-R5 in the

absence and presence of increasing concentrations of cyanide ion are given in Figures 7 and S45S48. The free receptors R1-R5 showed a signal at 11.697, 11.701, 11.821, 11.951 and 12.400 ppm, respectively for the N-H proton (δNH). A plot of δNH values versus Hammett’s σp values was found to linear with positive slope (r 0.99; Fig. 6). The positive slope indicated that the

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acidity of N-H proton increased with an increase in electron withdrawing power of the substituent. The electron withdrawing substituent would reduce the electron density on the Natom which in turn makes the N-H proton relatively more acidic. Such an electron deficient N-

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atom will behave as a poor electron donor in ICT transition (as seen in electronic spectral studies) and consequently makes the nucleophilc addition of cyanide onto the C=C bond

cr

relatively easier (as discussed above).

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As shown in the figure 7, free receptor R3 showed a peak at δ 7.643 ppm corresponding to the olefinic proton (marked as Ha). Upon addition of 0.5 equivalent of CN- ion, this signal gets

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reduced and disappeared after the addition of 1 equivalent of cyanide ion. While a new signal appeared at 4.168 ppm corresponding to the same proton in a new environment (marked as Hb).

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This observation showed that as a result of nucleophilic addition of CN- to C=C bond, the olefinic proton (Ha) of R3 gets converted into alkane proton in the product (Hb) [27, 37-39]. All

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the other receptors showed similar spectral changes with the addition of cyanide ion. The

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nucleophilic addition of cyanide ion that occurred at electropositively polarized C-atom destruct the π-conjugation between the donor and acceptor moieties and lead to switch-off of the ICT transition, resulting in the blue shift of the ICT transition band. Thus, the mechanism of cyanide ion sensing by these receptors occurs via nucleophilic addition of cyanide to the indole C=C bond. This proposed mechanism explains the effect of pH on sensing as shown in the Figure S21. In basic pH, the colour of the receptor itself bluish green which may be due to the deprotonation of N-H by hydroxide ions. Such an electron rich N-atom would exhibit relatively more intense ICT transition and thus would polarize the C=C bond relatively more and consequently the addition of cyanide will occur easily. However, in acidic medium the protonation of the N-atom would prevent the ICT transition and thus the nuclophilic addition of cyanide to the C=C bond.

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In order to further support the proposed mechanism,

13

C NMR spectral titration studies

were also carried out with R2 and R3 as representative cases. The spectra thus obtained are depicted in figures 8 and S49. As seen from the figure 8, in the free R3, the peak appeared at

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125.65 and 108.58 ppm corresponds to the indole carbons C1 and C2, respectively were shifted to 47.52 and 62.45 in the product after the addition of cyanide ion. Further, the peak due to the

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C2 suggested that it possess anionic character [27, 40]. Also, a new signal appeared at δ 116.49

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ppm is due to the added cyanide C-atom. The receptor R2 also showed similar spectral behaviour upon addition of cyanide ion (Fig. S49). Electrochemical studies

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3.5

As the cyanide sensing mechanism involves turn-off of the ICT transition between

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electron donor N-H and electron acceptor quinone in these receptor molecules, measurement of electro-reduction potential of the quinone ring before and after the addition of cyanide ion would

d

shed more light on the proposed mechanism. The electro-reduction potentials of the receptors

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R1-R5 were measured with addition of different concentrations of cyanide ion by using Differential Pulse Voltammetry (DPV) technique in acetonitrile. The DP voltammograms are shown in figures 9 and S50-S53. All the receptors exhibited a typical voltammogram for the electro-reduction of the quinone ring with two reduction peaks (at Epc = R1: -0.176, -0.792; R2: 0.152, -0.768; R3: -0.144, -0.756; R4: -0.136, -0.748 and R5: -0.096, -0.712 V). The first peak at a lower negative potential corresponds to the formation of radical anion (Q.-) and the second peak at a relatively higher negative potential corresponds to the formation of dianion (Q2-) [41]. As seen from the voltammograms, with the incremental addition of cyanide ion both the reduction peaks of the receptors shifted to lesser negative potential with a concurrent decrease in current density. That is electro-reduction of the quinone becomes relatively easier upon addition

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of cyanide ion. This is due to the fact that nucleophilic addition of cyanide ion to the C=C bond terminated the ICT transition and thus decreased the electron density on the quinone ring, which makes its electro-reduction easier [27]. Theoretical computations

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3.6

The electronic properties of these receptors before and after the addition of cyanide ion

cr

was computed using DFT calculations at the B3LYP/6-311G level basis set using Gaussian 03

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package [42]. The optimized geometries and the relevant frontier molecular orbitals (HOMO and LUMO) are shown in Figures S54-S56. As seen from the figures, HOMO is concentrated on the

an

indole moiety (donor) and LUMO is localized on the quinone moiety (acceptor). Such a distribution of MO’s is prerequisite for a compound to be a good ICT probe [43,44]. The energy

M

corresponds to the ICT transition (∆E) in the free receptor and their products are given in Table S2. The observed results showed that the energy (∆E) required for the ICT transition, in the

d

receptors, increased upon addition of cyanide ion, which is due to the interruption of conjugation

Ac ce pt e

between the donor and acceptor moiety after the addition of cyanide ion. Thus the theoretical study is in good agreement with the blue shift observed in the electronic spectral studies. From Figure 1, it is interesting to note that in a similar type of receptor I due to the strong electron withdrawing nature of DDQ, the indole C=C bond was polarized to a larger extent forming an electropositive C-atom, with Mulliken charge of 0.216 eV (R = H), for the nucleophilic addition of cyanide ion to occur [25]. However, in the case of II, naphthoquinoneindole ensemble, such an electropositive C-atom (R = H; 0.135 eV) was not generated and hence it senses cyanide through H-bond formation with the N-H and not via addition reaction [26]. Similar should be the case with III (benzoquinone-indole ensemble) also with an equally electropositive C-atom (for R=H; 0.134 eV). In the present study theoretical calculations

Page 17 of 38

18

indicated that the Mulliken charge on the reaction site i.e. the C-atom is 0.162 eV (R = H), which is positive enough for the addition reaction to occur. Hence, the electron withdrawing nature of the quinone and the extent of polarization of the C=C bond determine the nature of the

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mechanism of sensing of cyanide in such receptors wherein ICT transition occurs via C=C bond which is susceptible to addition and the donor in ICT transition is a HBD moiety (N-H). Practical application

cr

3.7

us

To explore the practical applicability of the receptors, easy to use, inexpensive test strips were prepared by immersing filter paper into an aqueous solution of R3 (as a representative case)

an

and drying in air (Fig. 10). The cyanide solutions of various concentrations were prepared in deep well water by dissolving required quantity of sodium cyanide. The composition of the deep

M

well water employed in the present study is: (all in mg/L except pH) pH 8.01; Total alkalinity 363; Total hardness 262; Total dissolved solids 1387; Cl− 206; F− 1.06; SO42− 41. As shown in

d

the figure, when the test strips were immersed in variation concentration of cyanide in water, the

Ac ce pt e

colour of the strips immediately changed from blue to yellow. Therefore, the prepared strips are an effective test-kit for the detection of cyanide ion in water with high selectivity in real time applications. 4.

Conclusion

A series five new benzoquinone based chemodosimeters for selective sensing of cyanide ion has been designed, characterized and screened. These receptors sense cyanide ion selectively and sensitively in water with a striking colour change that can easily be seen visually. The 1H and

13

C NMR spectral studies indicated that the receptors sense cyanide ion by nucleophilic

addition of cyanide ion to C=C bond of indole ring. The binding constant values, stoichiometry of the binding and detection limits were determined using absorption and emission spectral

Page 18 of 38

19

titration studies. The detection limit of the receptor found to be in the nM range which is much lower than the permissible limit of cyanide ion in drinking water set by WHO (1.9 µM). The proposed mechanism of sensing has been verified using electrochemical and theoretical studies.

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Linear structure-activity relationship between λICT, binding constant and δNH and the Hammett’s substituent constants were observed. Further, the strips developed can be used as a convenient

cr

and effective CN- test-kit in the field measurement.

us

Acknowledgement

One of the authors (P.J.) is thankful to the UGC, New Delhi for the award of UGC-BSR

an

Fellowship in Sciences for Meritorious Students. References

M

[1]. Z. Xu, X. Chen, H. N. Kim, J. Yoon, Sensors for the optical detection of cyanide ion,

d

Chem. Soc. Rev., 39 (2010) 127-137.

[2]. H. Y. Jo, S. A. Lee, Y. J. Na, G. J. Park, C. Kim, A colorimetric Schiff base chemosensor

Ac ce pt e

for CN- by naked eye in aqueous solution, Inorg. Chem. Commun., 54 (2015) 73-76. [3]. S. W. Thomas, G. D. Joly, T. M. Swager, Chemical sensor based on amplifying fluorescent conjugated polymers, Chem. Rev., 107 (2007) 1339-1386. [4]. C. Y. Kim, S. Park, H. J. Kim, Indocyanine based dual optical probe for cyanide in HEPES buffer, Dyes Pigments, 130 (2016) 251-255. [5]. X. S. Shang, N. T. Li, Z. Q. Guo, P. N. Liu, Selective “turn-on” probes for CN- based on a fluorophore skeleton of 1,3-dihydroisobenzofuran, Dyes Pigments, 132 (2016) 167-176. [6]. X. Huang, X. Gu, G. Zhang, D. Zhang, A highly selective fluorescence turn on detection of cyanide based on the aggregation of tetraphenyl ethylene molecules induced by chemical reaction, Chem. Commun., 48 (2012) 12195-12197.

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[7]. T. Gunnlaugsson, M. Glynn, G. M. Tocci, P. E. Kruger, F. M. Pfeffer, Anion recognition and sensing in organic and aqueous media using luminescent and colorimetric sensor, Coord. Chem. Rev., 250 (2006) 3094-3117.

ip t

[8]. D. S. Kim, Y. M. Chung, M. Jun, K. H. Ahn, Selective colorimetric sensing of anions in aqueous media through reversible covalent bonding, J. Org. Chem., 74 (2009) 4849-

cr

4854.

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[9]. Y. C. Yang, J. A. Barker, J. R. Ward, Decontamination of chemical welfare agents, Chem. Rev., 92 (1992) 1729-1743.

an

[10]. Guidelines for Drinking- Water Quality, World Health Organization, Geneva, Switzerland (1996).

M

[11]. T. T. Christison, J. S. Rohrer, Direct determination of free cyanide in drinking water by

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(2007) 31-39.

d

ion chromatography with pulsed amperometric detection, J. Chromatogr. A, 1155

[12]. T. Suzuki, A. Hioki, M. Kurahashi, Development of a method for estimating an accurate equivalence point in nickel titration of cyanide ions, Anal. Chim. Acta, 476 (2003) 159-165.

[13]. A. R. Surleva, V. D. Nikolova, M. T. Neshkova,

A new generation of cyanide ion-

selective membranes for flow injection application: Part II. Comparative study of cyanide flow-injection detectors based on thin electroplated silver chalcogenide membranes, Anal. Chim. Acta, 583 (2007) 174-181.

[14]. Y. Tian, P. K. Dasgupta, S.B. Mahon, J. Ma, M. Brenner, J. Wang, G. R. Boss, A disposable blood cyanide sensor, Anal. Chim. Acta, 768 (2013) 129-135.

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[15]. M. Tomasulo, F. M. Raymo, Colorimetric detection of cyanide with a chromogenic oxazine, Org. Lett., 7 (2005) 4633-4636. [16]. S. S. Sun, A. J. Lees, Anion recognition through hydrogen bonding: a simple, yet

ip t

highly sensitive, luminescent metal complex sensor, Chem. Commun., (2000) 16871688.

cr

[17]. H. Miyaji, J. L. Sessler, Off-the-shelf colorimetric anion sensor, Angew. Chem. Int.

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Ed., 40 (2001) 154-157.

[18]. L.Yang, X. Li, J. Yang, Y. Qu, J. Hua, Colorimetric and ratiometric near infra-red

an

fluorescent cyanide chemodosimeter based on phenazine derivatives, Appl. Mater. Interfaces, 5 (2013) 1317-1326.

M

[19]. H. Yoon, C. H. Lee, Y. H. Jeong, H. C. Gee, W. D. Jang, A Zinc porpyrin based molecular probe for the determination of contamination in commercial acetonitrile,

d

Chem. Commun., 48 (2012) 5109-5111.

Ac ce pt e

[20]. J. F. Xu, H. H. Chen, Y. Z. Chen, Z. J. Li, L. Z. Wu, C. H. Tung, Q. Z. Yang, A colorimetric and fluorometric dual-modal chemosensor for cyanide in water, Sens. Actuators, B, 168 (2012) 14-19.

[21]. J. L. Sessler, D. G. Cho, The Benzil Rearrangement Reaction:  Trapping of a Hitherto Minor Product and Its Application to the Development of a Selective Cyanide Anion Indicator, Org. Lett., 10 (2008) 73-75.

[22]. W. C. Lin, J. W. Hu, K. Y. Chen, A ratiometric chemodosimeter for highly selective naked-eye and fluorogenic detection of cyanide, Anal. Chim. Acta, 893 (2015) 91-100.

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[23]. J. W. Hu, W. C. Lin, S. Y. Hsiao, Y. H. Wu, H. W. Chen, K. Y. Chen, An indanedionebased chemodosimeter for selective naked-eye and fluorogenic detection of cyanide, Sens. Actuators B, 233 (2016) 510-519.

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[24]. S. T. Wang, Y. W. Sie, C. F. Wan, A. T. Wu, A reaction based fluorescent sensor for detection of cyanide in aqueous media, J. Lumin., 173 (2016) 25-29.

cr

[25]. C. Arivazhagan, R. Bprthakur, R. Jagan, S. Ghosh, Bensoindolium-Triarylborane

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conjugates: Ratiometric fluorescent chemodosimeter for the detection of cyanide in aqueous medium, Dalton Trans., 45 (2016) 5014-5020.

an

[26]. S. Wang, X. Fei, J. Guo, Q. Yang, Y. Li, Y. Song, A novel reaction based colorimetric and ratiometric fluorescent sensor for cyanide anion with a large emission shift and

M

high selectivity, Talanta, 148 (2016) 229-236.

[27]. R. Manivannan, K. P. Elango, Structure-reactivity correlation in selective colorimetric

d

detection of cyanide in solid, organic and aqueous phases using quinone based

Ac ce pt e

chemodosimeter, New J. Chem., 40 (2016) 1554-1563.

[28]. P. Jayasudha, R. Manivannan, K. P. Elango, Selective sensing of cyanide in aqueous solution by quinone-indole ensembles - quantitative effect of substituents on the HBD property of the receptor moiety, Sens. Actuators B, 242 (2017) 736-745.

[29]. J. S. Yadav, B. V. S. Reddy, T. Swamy, Bi(OTf)3-catalyzed conjugate addition of indoles to p-quinones: A facile synthesis of 3-indolyl quinones, Tetrahedron Lett., 44 (2003) 9121-9124.

[30]. J. S. Yadav, B. V. S. Reddy, T. Swamy, InBr3-catalyzed conjugate addition of indoles to p-quinones: A facile synthesis of 3-indolyl quinones, Synthesis, 1 (2004) 106-110.

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[31]. P. L. Alvarado, C. Avendano, J. C. Menendez, Efficient multigram-scale synthesis of three 2,5-dihalobezoquinones, Syn. Commun., 32 (2002) 3233-3239. [32]. J. Shorter, Correlation Analysis of Organic Reactivity, Research Studies Press,

[33]. P. Job, Ann. Chim. Phys., 9 (1928) 113-203.

cr

[34]. R. L. Scott, Recl. Trav. Chim. Pays-Bas Belg, 75 (1956) 787-789.

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Letchworth (1982).

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[35]. J. Ma, Y. Liu, L. Chen, Y. Xie, L. Y. Wang and M. X. Xie, Spectroscopic investigation on the interaction of 3,7-dihydroxyflavone with different isomers of human serum

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albumin, Food Chem., 132 (2012) 663-670.

[36]. Analytical Methods Committee, Analyst, 112 (1987) 199-204.

M

[37]. P. Jayasudha, R. Manivannan, K. P. Elango, Simple colorimetric chemodosimeter for selective sensing of cyanide ion in aqueous solution via termination of ICT transition

d

by Michael addition, Sens. Actuators B, 221 (2015) 1441-1448.

Ac ce pt e

[38]. S. Park, H. J. Kim, Reaction based chemosensor for the reversible detection of cyanide and cadmium ions, Sens. Actuators, B, 168 (2012) 376-380.

[39]. R. Manivannan, A. Satheshkumar, K. P. Elango, Highly selective colorimetric/ fluorometric chemodosimeters for cyanide ion in aqueous solution by Michael addition

to carbon atom possessing different polar substituents, Tetrahedron Lett., 55 (2014) 6281-6285.

[40]. Q. Li, Y. Cai, H. Yao, Q. Lin, Y. R. Zhu, H. Li, Y. M. Zhang, T. B. Wei, A colorimetric and fluorescent cyanide chemosensor based on dicyanovinyl derivatives: utilization of the mechanism of intramolecular charge transfer blocking, Spectrochim. Acta, Part A, 136 (2015) 1047-1051.

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[41]. V. A. Nikitina, R. R. Nazmutdinov, G. A. Tsirlina, Quinones Electrochemistry in Room-Temperature Ionic Liquids, J. Phys. Chem. B, 115 (2011) 668-677. [42]. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,

J. R.

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Cheeseman, J. A. Jr., Montgomery, T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.

cr

A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,

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M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.

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Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S.

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Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J.

d

Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.

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Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision D.01; Gaussian, Inc., Wallingford CT (2004).

[43]. A. Satheshkumar, E. S. H. El-Mossalamy, R. Manivannan, C. Parthiban, L. M. AlHarbi, S. A. Kosa, K. P. Elango, Anion induced azo-hydrazone tautomerismfor the selective colorimetric sensing of fluoride ion, Spectrochim. Acta A, 128 (2014) 798– 805.

[44]. Z. Luo, B. Yang, C. Zhong, F. Tang, M. Yuan, Y. Xue, G. Yao, J. Zhang, Y. Zhang, A dual-channel probe for selective fluoride determination and application in live cell imaging, Dyes Pigments, 97 (2013) 52–57.

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Figure captions Fig. 1. Receptors with Mullican charges Fig. 2. Colour changes observed in aq. HEPES buffer solution of R3 (2.5x10-4 M) upon addition

ip t

of various anions Fig. 3. UV-Vis spectra of free receptors R1-R5 (6.25x10-5 M) in aq. HEPES buffer

M) in aq. HEPES buffer

us

5

cr

Fig. 4. UV-Vis spectra of R3 (6.25x10-5 M) with incremental addition of cyanide ion (0-6.25x10-

Fig. 5. Fluorescence spectra of R3 (1.625x10-5 M) with incremental addition of cyanide ion (0-

an

1.625x10-5 M ) in aq. HEPES buffer (Inset: Solutions of R3 and R3+CN- under UV light) Fig. 6. Correlation of binding constants (K) and δNH with Hammett’s substituent constants (σp)

ion in DMSO-d6 13

C NMR spectra of R3 with addition of (A) 0 eqv. (B) 1.0 eqv. of cyanide ion in

Ac ce pt e

DMSO-d6

d

Fig. 8.

M

Fig. 7. 1H NMR spectra of R3 with addition of (A) 0 eqv. (B) 0.5 eqv. (C) 1.0 eqv. of cyanide

Fig. 9. Changes in redox properties of R3 upon addition of cyanide ion in acetonitrile Fig. 10. Colour changes of test strips upon dipping in cyanide ion solution in deep well water Table 1. Data obtained from UV-Vis spectra upon titration of R1-R5 with CN- ion Table 2. Fluorescence spectral data for the interaction of the receptors with CN-ion

Page 25 of 38

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cr

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26

O

O

O

CN -0.188

Cl

-0.154

R O

0.216

0.135 N

H

II

Ac ce pt e

I

N H

d

O

-0.133

R

M

Cl

O

O Br R

-0.181

Br

R

O

0.134

III

N H

0.162

N H

R

Fig. 1

Page 26 of 38

Fig. 2

Ac ce pt e

d

M

an

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cr

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27

Page 27 of 38

Ac ce pt e

d

M

an

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cr

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28

Fig. 3

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Ac ce pt e

d

M

an

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cr

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29

Fig. 4

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cr

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30

R3+CN -

Ac ce pt e

d

M

an

R3

Fig. 5

Page 30 of 38

Ac ce pt e

d

M

an

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cr

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31

Fig. 6

Page 31 of 38

cr

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32

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O Br

Hb

O

C

NH H b CN

M

Ha

an

Br

d

B

Hb

Ha

Ac ce pt e

O

Br

Br

A

O

Ha

NH

Fig. 7

Page 32 of 38

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cr

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33

O

Br

an

Br c2 O

NH NC c1

Br c2

d

O

C2

Ac ce pt e

C1

O

C1

M

B

Br

C2

New CN

c1 NH

A

Fig. 8

Page 33 of 38

Ac ce pt e

d

M

an

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cr

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34

Fig. 9

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Ac ce pt e

d

M

an

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cr

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35

Fig. 10

Page 35 of 38

Table 1.

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cr

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36

Receptor

In Receptor λICT (nm)

log ε

In complex λICT (nm)

R1

559

3.98

412

147

489

1.2x104

R2

553

4.02

414

139

487

3.2x104

R3

549

4.00

494

3.6x104

Association constant (M-1)

d

M

Blue shift Isosbestic ∆λICT (nm) point (nm)

148

R4

530

4.04

404

126

486

5.2x104

R5

504

3.90

380

124

467

5.8x104

Ac ce pt e

401

Page 36 of 38

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cr

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37

Receptor

λex(nm)

λem(nm)

Binding constant (M-1)

R1

320

426

6.8x104

58

0.21

Quantum yield (Ф) after CNaddition 0.46

R2

320

425

8.4x104

43

0.22

0.51

R3

321

424

d

an

Table 2.

19

0.28

0.58

R4

360

425

10x104

15

0.37

0.66

R5

363

424

11x104

9

0.43

0.72

M

Detection limit (nM)

Ac ce pt e

8.7x104

Quantum yield (Ф) for free receptor

Page 37 of 38

38

Author Biographies

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K.P.Elango received his PhD degree in the area of Coordination Complexes. He is now working as a Professor in Chemistry in Gandhigram Rural Institute-Deemed University. His area of research interests includes development of chemosensors and coordination complexes.

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P. Jayasudha has obtained her Master Degree in Chemistry in 2014 and now is pursuing for her Doctoral degree.

Ac ce pt e

d

M

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R. Manivannan has obtained his Doctoral degree recently from Gandhigram University and now working as a Post-Doctoral Fellow in Chungnam National University, Korea.

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