sensors for the optical detection of cyanide ion · sensors for the optical detection of cyanide...

Sensors for the optical detection of cyanide ion

Zhaochao Xu,w Xiaoqiang Chen,w Ha Na Kim and Juyoung Yoon*

Received 17th April 2009

First published as an Advance Article on the web 4th September 2009

DOI: 10.1039/b907368j

This tutorial review focuses on recent developments arising from studies of optical sensors

for cyanide ions, which are categorized by approaches involving cyanide selective receptors,

the utilization of metal coordinated complexes, and chemodosimeters.

Introduction

Although substances containing cyanide have been used as

poisons for centuries, it was not until 1782 that this anion was

first isolated by the Swedish chemist Scheel.1 The extreme

toxicity of cyanide in physiological systems, as well as the

continuing environmental concern caused by its widespread

industrial use, has led to considerable research into the

development of methods for cyanide detection. Various methods

used previously to analyze cyanide employ titrimetric,2

voltammetric,3 potentiometric,4 and electrochemical methods,5

as well as ion chromatography,6 etc. However, these methods

often require extensive, time consuming procedures that

involve the use of sophisticated instrumentation with high

detection limits. Optical sensors for cyanide, in which a change

in color and/or fluorescence intensity (or emission wavelength)

is monitored, have been studied actively over the past ten years

due to their simple, inexpensive, and rapid implementation.

Generally, three different approaches, which are shown

schematically in Fig. 1, have been employed to design optical

sensors for cyanide ions. The most popular strategy involves the

use of sensors in which the binding sites and signaling subunits

are linked covalently. In this case, interaction of cyanide with the

binding site causes a change in color or fluorescence of the

signaling subunit. A coordination complex-based displacement

approach has also been used. In these sensors, the introduction

of cyanide ions leads to regeneration of spectroscopic behavior

of the noncoordinated indicator. A third method for the

determination of cyanide is known as a chemodosimeter

approach. These types of sensors rely on the occurrence of

specific, most often irreversible chemical reactions, which take

place upon an interaction with cyanide. Compared to other

types of anion selective optical chemosensors,7–12 cyanide

selective optical chemosensors take advantage of two significant

and characteristic properties of cyanide, its strong nucleo-

philicity and high binding affinity towards copper ions. Thus

far, cyanide sensing has been a part-topic in relatively few early

review articles.8,10,13,14 To the best of our knowledge, cyanide

sensors have not been reviewed thoroughly in recent years, even

though some cyanide selective colorimetric sensors were recently

reported.15 This review begins with a brief discussion of the

source and toxicity of cyanide, and then moves to a discussion

of cyanide sensors, which are classified according to the above-

mentioned approaches.

Cyanide sources and toxic effects

Sources

Cyanide containing salts are widespread chemicals found in

surface water originating not only from industrial waste but

also from biological sources. Cyanide is used in many chemical

processes, such as electroplating, plastics manufacturing, gold

and silver extraction, tanning, and metallurgy.16,17 In addition,

Department of Chemistry and Nano Science and Department ofBioinspired Science, Ewha Womans University, Seoul 120-750, Korea.E-mail: [email protected]; Fax: +82-2-3277-2384;Tel: +82-2-3277-2400

Zhaochao Xu

Zhaochao Xu received hisPhD in 2006 from DalianUniversity of Technologyunder the supervision of Prof.Xuhong Qian. Subsequently hejoined the group of JuyoungYoon at Ewha WomansUniversity as a postdoctoralfellow. Since October 2008 hehas been a Herchel SmithPostdoctoral Research Fellowat the University ofCambridge in the group ofDavid R. Spring.

Xiaoqiang Chen

Xiaoqiang Chen was born in1980 in China. He obtainedhis PhD in 2007 from DalianUniversity of Technology(China) under the supervisionof Prof. Xiaojun Peng. He ispresently working as a post-doctoral fellow in the group ofProf. Juyoung Yoon at EwhaWomans University, Korea.

w Contributed equally to this work.

This journal is �c The Royal Society of Chemistry 2010 Chem. Soc. Rev., 2010, 39, 127–137 | 127

TUTORIAL REVIEW www.rsc.org/csr | Chemical Society Reviews

cyanide is a chemical warfare agent.1 Various industries,

including petrochemical, gold mining, metal electroplating,

photographic, steel manufacturing, are responsible for cyanide

pollution. The production of nitrile, nylon and acrylic plastics

is also associated with environmental concerns caused by

cyanide. Biological sources of cyanide include bacteria, fungi

and algae, which produce this ion as part of their nitrogen

metabolic pathways. Vegetables containing cyanogenic glyco-

sides are sources of cyanide ingestion in humans and animals.

Dietary foodstuffs that contain moderate to high levels of

cyanogenic glycosides include cassava, a dietary staple in

several regions of Africa, as well as other common foods such

as lima beans, sorghum, linseed, kernels of fruits, sweet

potatoes and bamboo shoots.17 Tobacco smoke is also a

common source of cyanide and can lead to high levels of this

ion in the blood. Other potential sources of cyanide in humans

and animals are sodium nitroprusside, succinonitrile and

organic thiocyanates.17 The United States Environmental

Protection Agency (EPA) has set the maximum contaminant

level (MCL) for cyanide in drinking water at 0.2 ppm.

Toxicity and metabolic effects

The LD50 (estimated dose that is lethal to 50% of the exposed

population) of hydrogen cyanide and cyanogen chloride has

been reported to be 2500–5000 mg.min/m3 and 11000 mg.min/m3.

The LD50 of hydrogen cyanide in humans is 1.0 mg/kg, and

the estimated LD50 for cyanide solutions applied to the skin is

approximately 100 mg/kg.1 Cyanide can affect many functions

in the body, including the vascular, visual, central nervous,

cardiac, endocrine, and metabolic systems. Perhaps the best

known effect of cyanide is its inhibition of respiration, which is

caused by the inhibition of the terminal oxidase (cytochrome

oxidase) of the mitochondrial respiratory chain. Sublethal doses

of cyanide cause a decrease in the rate of glycolysis and inhibit the

operation of the TCA cycle. Cyanide also acts as an inhibitor

of metallo-enzymes and of some non-metallo-enzymes that

function through the intermediacy of Schiff bases.1,16 The

toxicodynamic effects of cyanide can depend on the dose,

route and speed of administration, the chemical form of

cyanide and other factors including gender, age, weight, stress

level, and general physical condition.

Sensors based on the covalently linked binding site

and signaling subunit approach

Although cyanide is not a strong hydrogen bonding acceptor

compared to other anions, several cyanide selective sensors

that rely on hydrogen bonding interactions have been

described. In addition, ditopic systems bearing two metal sites

were examined as cyanide selective receptors, which function

in organic solvents.

Hydrogen bonding based receptors

Lees et al. described a luminescent rhenium(I) polypyridyl-

based receptor 1 for the recognition of anions (Fig. 2).18 This

artificial receptor shows high affinity for halides, cyanide and

acetate anions with binding constants as high as 104–105 M�1

in CH2Cl2. The overall order of binding affinity was found to

be CN� 4 F� 4 I� 4 Cl� E Br� E OAc� c H2PO4� 4

NO3� 4 ClO4

�. Although this affinity trend was not clearly

explained, a combination of interactions involving electro-

static forces, hydrogen bonding strengths and steric effects

have been reported to affect the binding affinity of receptors

toward anions.

Fig. 1 Three approaches for chemosensors: (a) chemosensor bearing

a signaling subunit as well as a binding site; (b) displacement

approach; (c) chemodosimeter.

Ha Na Kim

Ha Na Kim received the BSdegree in Ewha WomansUniversity. She then was giventhe MS degree in medicalscience by Seoul NationalUniversity in 2006. She is ona doctoral course in Prof.Juyoung Yoon’s researchgroup in Ewha WomansUniversity.

Juyoung Yoon

Juyoung Yoon received hisPhD (1994) from TheOhio State University. Aftercompleting postdoctoralresearch at UCLA and atScripps Research Institute, hejoined the faculty at SillaUniversity in 1998. In 2002,he moved to Ewha WomansUniversity, where he iscurrently a Professor of theDepartment of Chemistryand Nano Science and theDepartment of BioinspiredScience. His research interestsinclude investigations of

fluorescent chemosensors, molecular recognition and organoEL materials.

128 | Chem. Soc. Rev., 2010, 39, 127–137 This journal is �c The Royal Society of Chemistry 2010

Anzenbacher and Castellano et al. designed the novel

cyanide sensor 2 based on the changes in the anion-induced

luminescence lifetime (Fig. 2).19 The addition of fluoride and

cyanide to this sensor caused significant changes in the UV-vis

and steady-state emission properties of compound 2 in

CH2Cl2–CH3CN (98 : 2, v/v). Quenching of the steady state

photoluminescence was observed upon the addition of

cyanide. In addition, cyanide causes a change in the lumines-

cence lifetime of the sensor from 377 to 341 ns in the same

solvent system.

Vilar et al. recently utilized azo-phenylthiourea compounds

3a and 3b as probes for cyanide (Fig. 2).20 In methanol, the

dyes undergo color changes from pale orange to red in the

presence of cyanide with a detection limit of 8 ppm. In DMSO,

cyanide induces a color change (to dark purple) as does

fluoride (to blue), while CH3CO2� and H2PO4

� (both to

violet/red) also promote color changes. The authors suggested

that the origin of the color changes was not a simple change in

hydrogen-bonding interaction, but rather a process that

involves the deprotonation of thiourea NH groups. The

optical properties of compound 3a incorporated in nano-

structured Al2O3 films have been determined. An aqueous

solution of cyanide induces a color change in these films,

which can be used to detect cyanide at 2.6 ppm.

Metal complex based receptors

Hong et al. reported the results of a study on Zn-porphyrin/

crown ether conjugates.21 These ditopic neutral receptors

(4a and 4b) contain a Lewis-acidic binding site (zinc porphyrin

moiety) and a Lewis-basic binding site (crown ether moiety)

(Fig. 3a). The two receptors display a color change from the

original red of Zn-porphyrin to green selectively in the

presence of sodium cyanide. The origin of this unique color

change was proposed to be associated with the binding of

cyanide in a ditopic manner, in contrast to other sodium salts,

which are bound to the receptors in a monotopic fashion.

Chen et al. described a similar approach to sensor design

utilizing the ditopic characteristics of aza-crown ether-capped

porphyrins 5a and 5b (Fig. 3b).22 These artificial receptors

selectively recognize sodium cyanide and potassium cyanide as

a result of ditopic binding in methanol. The binding of receptor

5a to sodium cyanide is 56 times stronger than that for

potassium cyanide, whereas the selectivity of 5b for potassium

cyanide is 12 times higher than that for sodium cyanide.

Displacement approach

Among the various systems designed to detect cyanide, sensors

utilizing the affinity of this anion for copper have attracted

special attention. Cyanide reacts with copper ions to form

stable [Cu(CN)x]n� species. One of the most important

advantages of sensors based on this chemistry is that they

should be operable in aqueous solutions.

Cu complex

Mareque-Rivas et al. designed a cyanide sensor system that

considers the ability of copper ions to affect the kinetics of

electron transfer across a copper binding, self assembled

monolayer (SAM) to a negatively charged redox probe in

solution and the ability of (H)CN to bind and remove copper

ions (Fig. 4).23 The SAM-modified gold electrode exhibits a

charge transfer resistance value (RCT) of 32 O cm2. An

inspection of the impedance plots showed that the RCT values

increase with increasing cyanide concentration. Nanomolar

concentrations of cyanide (0.03 ppb detection limit), even at

pH 7.3, could be detected using this method.

Li et al. examined light-emitting polyacetylene bearing

imidazole moieties in the context of a new type of cyanide

sensor.24 The polymer sensor displays selective fluorescence

quenching in the presence of Cu2+. Interestingly, the

Cu2+-promoted luminescence quenching can be inhibited by

the addition of cyanide, as shown in Fig. 5.

Li and coworkers also employed the same strategy in the

design of a new imidazole-functionalized polyfluorene 6,

Fig. 2 Structures of receptors 1, 2, 3a and 3b.

Fig. 3 (a) Structures of ditopic receptors 4a and 4b. (b) Structures of

receptors 5a and 5b and their proposed ditopic binding modes.

Fig. 4 Proposed mechanisms of SAM-modified gold electrode detecting

cyanide.


which is a sensitive and selective cyanide chemosensor

(Fig. 6).25 The fluorescence of compound 6 was quenched

completely by Cu2+ at concentrations as low as 0.20 ppm. The

quenched fluorescence of a solution of compound 6 and Cu2+

was recovered upon the addition of cyanide with a detection

limit as low as 0.31 ppm.

The Mareque-Rivas group also used a combination of

tri-n-octylphosphine oxide (TOPO)-coated CdSe quantum

dots (QDs), 2,20-bipyridine (bipy) and CuCl2 (Fig. 7) to

fabricate a turn-on fluorescence cyanide probe.26 The ability

of bipyridine-bound copper(II) ions to quench the photo-

luminescence of hydrophobic CdSe quantum dots was used

advantageously in this cyanide selective, turn-on fluorescence

sensor. This QD system detects cyanide at 20–100 mM

concentrations at a physiological pH. TOPO-coated CdSe

QDs placed on a polystyrene film displayed a similar

‘‘On–Off–On’’ type change upon the addition of cyanide.

On the other hand, Dong et al. utilized CdTe quantum

dots as turn-on fluorescent sensors for cyanide.27 Copper

ion-modified CdTe quantum dots were prepared and the

quenched fluorescence due to Cu2+ was revived in the

presence of cyanide with a detection limit of 3.9 ppb at pH 7.0.

Qin and Li et al. recently reported that an old and inexpensive

compound, zincon (2-carboxy-20-hydroxy-50-sulfoformazyl-

benzene (7)), can be used as a highly sensitive and selective

chemosensor for cyanide in aqueous solutions with a detection

limit of 0.13 ppm (Fig. 8).28 When the Cu2+ concentration

increases, the peak intensity of the absorption maximum at

463 nm of this sensor decreases with the concurrent formation

of a new peak at ca. 600 nm. The addition of cyanide to the

resulting complex 7-I causes an increase in the absorption

band at 463 nm, which can be observed with the naked eye.

Yoon, Park and coworkers devised a simple method

for detecting cyanide ions in aqueous solution at pH 7.4.29

The fluorescent probe 8 designed for this purpose displays a

fluorescence quenching effect with Cu2+. Therefore, the

addition of cyanide induces ‘‘Off–On’’ type fluorescence

enhancement (Fig. 9). This sensing system has been incorpo-

rated into a microfluidic platform, in which the fluorescent

sensor 8-Cu2+ displays green fluorescence upon the addition

of cyanide. Finally, studies of biological applications using

Caenorhabditis elegans demonstrated that this system can be

employed for the in vivo imaging of cyanide.

Co complex

Recently, Zelder utilized the ‘‘base on’’/‘‘base off’’ coordination

of the intramolecular bound benzimidazole nucleobase of

vitamin B12 in the construction of a novel sensor for cyanide

(Fig. 10).30 In its ‘‘base on’’ conformation, the sensor is red

colored (lmax = 550, 520 and 361 nm) and the addition of

cyanide induces a color change to violet (lmax = 579, 542 and

368 nm). As a result, this system can be used for the specific

colorimetric detection of millimolar concentrations of cyanide

in water. Zelder and coworkers also employed a similar

strategy in the design of corrinoid derivatives 9a–9c, in which

the substitution of CoIII-bound water by cyanide enables

the rapid colorimetric detection of micromolar amounts of

cyanide (Fig. 11).31

Chemodosimeter approach

The exceptional nucleophilicity of cyanide has served as a

basis for the development of various chemodosimetric probes

for cyanide, in most cases in aqueous solutions. As shown

below, this approach has recently attracted the attention of

many groups.

C–C bond formation utilizing cyanohydrin reaction

Ahn et al. reported that the fluorescence signaling of anion

binding can be modulated by intramolecular H-bonding

Fig. 5 Schematic representation of Cu2+ and cyanide sensors based

on the fluorescence ‘‘turn-off’’ and ‘‘turn-on’’ of polyacetylenes.

Fig. 6 Schematic representation of cyanide sensor based on the

fluorescence ‘‘turn-off’’ and ‘‘turn-on’’ of 6.

Fig. 7 Cyanide QD (quantum dot) based probe.

Fig. 8 The speculated conversion cycle of zincon 7 in the presence of

Cu2+ and cyanide.


stabilization of anion–ionophore adducts.32,33 In a recent

report from this group,34 it was shown that a carbonyl

addition intermediate, such as compound 10-I, which is

stabilized by intramolecular H-bonding, is responsible for

the fluorescence enhancement observed in acetonitrile

(Fig. 12). In contrast, another possible intermediate, 10-II, is

believed to show fluorescence quenching. Moreover, the

formation of adduct 10-I should be favored over the alter-

native deprotonation process leading to compound 10-II,

which was confirmed by NMR analysis.

Ahn et al. extended this intramolecular H-bonding stabili-

zation concept to the design of a heteroditopic receptor 11a

containing both a crown ether and a trifluoroacetylcarboxanilide

group (Fig. 13). In this system, cyanide was added to the

trifluoroacetyl group to produce an alkoxide adduct that

interacts with the potassium ion bound to the crown ether

moiety. As a consequence of a highly cooperative ion-pair

interaction, this sensor selectively recognizes both potassium

and cyanide ions in acetonitrile solutions with an association

constant as high as 1.9 � 107 M�1. This affinity is two orders

of magnitude higher than that of 11b.35

The Ahn group also described a new probe 12 that displays

fluorescence quenching in the presence of cyanide in

MeOH–water (9 : 1) solutions but not when other anions are

present (Fig. 13).36

The intramolecular H-bonding stabilization concept serves

as the basis for the boradiazaindacene 13 derivative described

by Akkaya et al. (Fig. 14).37 This chemosensor displays a large

decrease in fluorescence intensity and a reversible color change

from red to blue in the presence of cyanide in CH3CN. Highly

fluorescent polymeric films doped with this sensor were also

prepared. The introduction of cyanide causes the color/

emission of the film to change from an orange/fluorescent to

a blue/nonfluorescent, and the addition of trifluoroacetic acid

reverses this change.

This strategy was used by Cheng et al. to design a

2-(trifluoroacetylamino)anthraquinone sensor 14 (Fig. 14),

which undergoes a ‘‘naked eye’’ observable, colorless to yellow

transformation when low concentrations (13 ppb) of cyanide

in CH3CN–H2O (95 : 5, v/v) are added.38 Cheng and

coworkers also devised a colorimetric probe 15 (Fig. 14) that

exhibits excellent selectivity for cyanide in CH3CN–H2O

(95 : 5, v/v). A change from colorless to yellow takes place

upon the addition of cyanide.39

Recently, Guo et al. reported a simple N-nitrophenyl

benzamide derivative 16 (Fig. 14) for the ‘naked-eye’ detection

of cyanide in DMSO–H2O (1 : 1, v/v).40 This sensor can detect

cyanide at concentrations as low as 23 ppb in the above

solvent system by utilizing the strong affinity of cyanide

toward the acyl carbonyl carbon.

One general process operating in enzymatic reactions

involves carbonyl activation by a properly located phenol

hydroxyl group that leads to the general acid catalysis of

nucleophilic addition. This strategy was adopted intelligently

by Kim and Hong et al. in the design of a cyanide sensing

system 17 (Fig. 15). As a consequence of activation by

hydrogen bonding with the phenolic group in the salicyl-

aldehyde moiety, the carbonyl group of compound 17 is

expected to undergo nucleophilic addition with cyanide.41

Studies show that the 1H NMR spectrum of compound 17

in the presence of cyanide does not contain a resonance for the

aldehyde proton (Ha, initially at 10.4 ppm) but instead shows a

new resonance at 5.6 ppm (Hb). The chemical shift of this

resonance is consistent with a cyanohydrin proton resulting

Fig. 9 Proposed binding mechanism of 8 with Cu2+ and cyanide.

Fig. 10 Structures of vitamin B12 and the binding mechanism with

cyanide.

Fig. 11 Structures of corrinoids 9a–9c and a schematic for the

binding mode with cyanide.

Fig. 12 A plausible equilibrium pathway for interaction of 10 with

cyanide.

Fig. 13 Structures of ferrocene derivatives 11a, 11b and 12.


from cyanide addition to the aldehyde moiety. Interestingly,

the addition of cyanide to compound 17 in DMSO also causes

a clear color change from light yellow to dark red.

Kim and Hong et al. extended this concept to the design

of a coumarin-based fluorescent chemodosimeter 18

containing a salicylaldehyde group (Fig. 16).42 Rapid proton

transfer of the phenol hydrogen in the excited state results

in a strong fluorescence of an aqueous solution of compound

18 at pH 7.4. Cyanide at concentrations of 260 ppb in

aqueous solution can be detected using this fluorescent

chemodosimeter.

Yoon and Park et al. applied this strategy for the activation

of a carbonyl group by an adjacent phenol in devising a

fluorescein aldehyde-based cyanide sensor 19 (Fig. 16).43 In

CH3CN–H2O (9 : 1, v/v), the ‘‘OFF–ON’’ type emission

change can be monitored at wavelengths 4500 nm. The

practical use of this probe was demonstrated by its incorporation

into a microfluidic platform for the selective detection of

cyanide in living cells.

Ahn et al. constructed N-acyl-triazene derivatives that serve

as simple and tunable chemodosimeters based on the strong

affinity of cyanide toward an N-acyl carbonyl carbon

(Fig. 17).44 Significant changes in the absorption spectrum

(from colorless to deep purple) take place when acetonitrile

solutions of N-acetyltriazene 20a are titrated with both

cyanide and F�. In contrast, the N-isopropanoyl-triazene

20b in acetonitrile shows a significant response to cyanide

and only a weak response to F�. The absorption properties of

both triazenes 20a and 20b are altered only by the addition

of cyanide (faint yellow to red–pink, lmax = 521 nm)

when methanol–water (9 : 1, v/v) is used as a solvent. This

observation is most likely due to the fact that only cyanide

adds to the acyl group of these sensors.

Sessler et al. employed the well-known benzil–cyanide

reaction (Fig. 18) in the design of a colorimetric method for

the detection of cyanide.45 The p-extended analogue of benzil

21a was selected for this purpose. This substance is soluble in a

70 : 30 (v/v) mixture of methanol–water (Fig. 19). Dilute

solutions of compound 21a in this medium are yellow and

become colorless when low concentrations of cyanide but not

other anions are added. Using a dilute solution of compound

21a (7.20 � 10�6 M) in 70 : 30 (v/v) MeOH–water, a limit of

detection o44 ppb can be realized and visualized by simple

naked eye analysis. Prior to this report, Sessler et al. also

described a novel probe 21b (Fig. 19) that undergoes benzil

rearrangement when treated with cyanide (Fig. 18) in ethyl

acetate. In this organic solvent, a yellow to colorless change

and large fluorescence enhancement are observed within

1 min.46

Sun et al. prepared two probes, 22a and 22b, that feature the

use of the dipyrrole carboxamide moiety for anion recognition

(Fig. 20a).47 These structurally simple anion probes exhibit

high selectivity for cyanide over other common inorganic

anions in partially aqueous environments [CH3CN–H2O

(9 : 1, v/v)]. Both compounds 22a and 22b respond to cyanide

only, because cyanohydrin derivatives (22b-I and 22b-II) are

generated (Fig. 20b). This process is associated with a color

change from colorless to yellow (Fig. 20b) and a fluorescence

change for compound 22a from blue to green.

C–C bond formation utilizing chromogenic oxazines

Raymo et al. designed a chromogenic oxazine that can be used

for the selective colorimetric detection of cyanide. In this

system, the [1,3]oxazine ring of compound 23 opens to form

a 4-nitrophenylazophenolate chromophore (23-I) in the

reaction with cyanide (Fig. 21).48,49 In acetonitrile, the addition

of cyanide causes a decrease in the original absorption band at

381 nm (pale yellow) with the concomitant appearance of a

new absorption band at 581 nm (red). In aqueous solutions,

a significantly higher amount of cyanide is required to elicit a

UV response. In order to overcome this limitation, a two-

phase system consisting of dichloroethane and phosphate

buffer (pH 9) was used in conjunction with phase transfer

catalysis. Micromolar concentrations of cyanide can be

detected using this two-phase system.

Fig. 14 Structures of probes 13–16.

Fig. 15 A plausible mechanism for the action of probe 17 with

cyanide.

Fig. 16 Reaction mechanism of 18 and 19 with cyanide.

Fig. 17 Proposed reactions of 20a and 20b with cyanide.


Tian et al. designed a highly sensitive and selective cyanide

chemosensor based upon oxazine derivatives (24a and 24b). In

this system, the C–O bond of the oxazine moiety cleaves at the

spiro center (24a-I and 24b-I) when nucleophilic cyanide

anions are present (Fig. 22).50 The addition of the cyanide

anion to the oxazines in MeCN–H2O solution [19 : 1, pH 7.6

phosphate buffer (7.6 mM)] results in a color change asso-

ciated with the disappearance of the absorbance at 343 nm and

the appearance of a new absorption band at 411 nm. These

sensors show very rapid responses to cyanide (ca. 30 s) with a

detection limit of 26 ppb.

C–C bond formation utilizing dicyano-vinyl group

Lee et al. recently reported that the new calix[4]pyrrole-based,

dual functional, chemodosimetric sensor 25 serves as a cyanide

selective indicator (Fig. 23).51 Complete bleaching of the color

of compound 25 (yellow) was observed when cyanide was

added even in the presence of an excess of another anion.

A large bathochromic shift from lmax = 374 nm to lmax =

403 nm was observed for compound 25 upon cyanide anion

complexation in CH3CN–DMSO (3%).

C–C bond formation utilizing pyrylium or acridinium

compounds

Garcıa, Martınez-Manez et al. utilized pyrylium salt-containing

polymers as colorimetric sensors for cyanide.52 The electro-

philic character of the pyrylium ring in probe 26 and the

nucleophilicity of cyanide combine to induce a remarkable

color change from yellow to red as a consequence of the

formation of the cyano-enone derivative 26-I in acetonitrile

(Fig. 24a). Based on this observation, the authors fabricated

methacrylic copolymer films containing the pyrylium probe

(Fig. 24b). This copolymer showed a gradual increase in the

537 nm band when cyanide was added at pH 11.

The results of studies on a selective chemodosimeter based

on the acridine moiety were recently reported by Tae et al.

Among the various anions, only cyanide in DMSO–water

(95 : 5, v/v) promotes the selective fluorescent quenching of

the acridinium salt 27 with an accompanying concomitant

color change from orange to pale blue (Fig. 25).53 As shown

in Fig. 25, this strategy takes advantage of the nucleophilic

addition of cyanide at the 9-position of the N-methylacridinium

group. The resulting adduct 27-I was formed initially, which

rapidly reacted with oxygen to produce acridinone 27-II.

C–C bond formation utilizing squaraine, croconium or

triarylmethane dyes

A new squaraine based chemodosimeter 28, which relies on the

nucleophilicity of cyanide and the highly electron-deficient

four-membered ring (Fig. 26), was described by Martınez-

Manez et al.54 Studies of this sensor led to the observation that

a colorimetric change in compound 28 in water–acetonitrile

(8 : 2, v/v, pH 9.5) takes place only in the presence of cyanide.

The addition of cyanide to the squaraine ring in compound 28

results in both the loss of acceptor properties of the ring and a

rupture of the electronic delocalization with the concurrent

disappearance of the 641 nm charge transfer band. Although

Fig. 18 Proposed mechanisms of the benzil–cyanide reaction and

benzil rearrangement reaction.

Fig. 19 Structures of 21a and 21b.

Fig. 20 (a) Structures of 22a and 22b. (b) Proposed cyanohydrins

formation from reaction of 22b with cyanide.

Fig. 21 Reaction of chemodosimeter 23 with cyanide.

Fig. 22 Reactions of chemodosimeters 24a and 24b with cyanide.

Fig. 23 Reaction of 25 with cyanide.


the reaction between probe 28 and cyanide does not occur

instantaneously, this sensor system displays high selectivity

toward cyanide and a detection limit of 2.5 ppm.

Cheng and Zhang et al.55 developed a near-infrared,

colorimetric chemodosimeter, based on the dye 1,3-bis-

(4-N,N-diethylamino-2-hydroxyl-phenyl)croconine sensor 29

(Fig. 26) that can be used to detect the cyanide anion at

pH 9.0 in ethanol–H2O (70 : 30) solution (pH 9.0, buffered

with TRIS). The addition of cyanide causes a decrease in

absorbance in the NIR region (823 nm) and an increase in

absorbance in the range of 550–725 nm with an isosbestic

point at 725 nm. A brown to dark green color change was

observed with the naked eye immediately, and the color

changed slowly to yellow after ca. 1 h.

Afkhami et al. designed an optical absorption based,

one-shot cyanide sensor that is formed by the immobilization

of methyl violet 30 on an acetylcellulose membrane.56 In

this system, cyanide ion reacts with the immobilized methyl

violet, resulting in a decrease in the absorbance of the film

at 598 nm (Fig. 27). The response time of this sensor was

ca. 8–12 min depending on the cyanide concentration, and the

method has a detection limit of 62 ppm. The color of this

one-shot sensor is readily and fully regenerated using a methyl

violet solution.

Kaur and Singh et al.57 recently employed triarylmethane–

leuconitrile as a cyanide sensor. The triarylmethane dye 31

in CH3CN can be used to detect cyanide in water selectively by

the occurrence of a dramatic color change from blue–green

to colorless (Fig. 28). This change was attributed to the

nucleophilic addition of cyanide. An instant ‘‘dip-in’’ sensor

comprised of compound 31 dyed on wool was developed in

this effort.

C–S bond formation

Wang et al. reported the results of an investigation of

compounds 32a and 32b containing donor–acceptor type

chromophores with well-tuned reactivity towards cyanide

(Fig. 29a).58 These sensor systems employ compound 32a for

the highly selective colorimetric detection of micromolar

concentrations of cyanide in the presence of other anions. In

addition, compound 32b has triple signaling properties

that are advantageous for the highly sensitive, reliable and

quantitative detection of cyanide. Cyanide can be detected at

concentrations as low as 26 ppb in DMF–H2O (99 : 1, v/v)

using probe 32b. Moreover, compound 32b offers the

capability for multiple signaling, including visible absorption,

a high contrast change in color, and absorption and fluores-

cence spectral changes in the visible and NIR wavelength

regions. The mechanism of action for compound 32b with

cyanide, explored by using a model system, involves cyanide

attack on the benzothiadiazole ring sulfur, followed by a

second addition of cyanide. The resulting imidosulfite adduct

is readily oxidized to form a more stable sulfamide (Fig. 29b).

C–B bond formation

Martınez-Manez et al. described the use of subphthalocyanine

33 as a probe for the ‘‘naked eye’’ detection of cyanide

(Fig. 30).59 In a 3% vol/vol aqueous solution, both fluoride

and cyanide induce a pink to pale yellow color change,

whereas the color change is remarkably selective to cyanide

in 5% vol/vol aqueous acetonitrile solutions of compound 33.

These results have been attributed to the solvent dependence

of the relative nucleophilicities of fluoride and cyanide caused

by hydrogen bonding and other solvation effects. The

detection limit of compound 33 for cyanide is as low as

0.1 ppm at pH 9.6 [CH3CN–CHES (0.01 M)], and ca. 10 ppm

at pH 7 [CH3CN–HEPES (0.01 M)].

Selective colorimetric and fluorimetric molecular probes 34a

and 34b (Fig. 30), which are based on a subphthalocyanine

dye, have been developed for cyanide detection by Palomares

and Torres et al.60 A distinct pink to colorless change was

observed upon the addition of cyanide to aqueous solutions

of these substances. The carboxysubphthalocyanine deri-

vative 34b anchored covalently to a transparent, mesoporous

Fig. 24 (a) Mechanism for reaction of the monomer 26 with cyanide.

(b) Structure of the sensing film.

Fig. 25 Mechanism of the reaction of 27 with cyanide.

Fig. 26 Structures of probes 28 and 29.

Fig. 27 The reversible addition mechanism of 30 with cyanide.

Fig. 28 The reversible addition mechanism of 31 with cyanide.


nanocrystalline, high-surface-area metal oxide film can be used

to detect low concentrations of cyanide ions in pure water with

no interference from other anions or cations.

Do and Lee et al.61 recently described a strategy involving

the coupling of borane as a donor and BODIPY as an

acceptor which resulted in the fabrication of a boron-based

sensor 35 (Fig. 31). This receptor showed a 3-fold enhance-

ment in fluorescence intensity in response to cyanide ions

as a consequence of an addition reaction (35-I) that blocks

intramolecular electron transfer.

Based on the hypothesis that cationic boranes may be

particularly well-adapted for cyanide complexation due to

the favorable Coulombic receptor–anion attractions, Gabbaı

et al. designed cationic boranes, such as compound 36a, that

serve as selective sensors for cyanide in aqueous solutions

(Fig. 32).62 The unusual cyanide binding property of

compound 36a was attributed to the favorable Coulombic

effects that increase the Lewis acidity of boron and strengthen

the receptor–cyanide interaction. Using the two receptors, 36a

and 36b, they demonstrated that the anion binding selectivity

of the cationic boranes can be tuned using both steric and

electronic effects. For example, the Lewis acidity of the

ammonium borane increases when the trimethylammonium

moiety in compound 36b is positioned ortho to the boron

center, thus making fluoride binding possible (Fig. 32). In

this case, increased steric crowding of the boron center

prevents the coordination of the larger cyanide anion. In

H2O–DMSO (6 : 4, v/v, HEPES 6 mM, pH 7), the cyanide

binding constant of compound 36a and the fluoride binding

constant of compound 36b are 3.9 � 108 and 910 M�1,

respectively.

Recently, Kawashima et al. reported new cationic triaryl-

borane 37 (Fig. 33) as a selective optical sensor for cyanide in

DMSO–HEPES (pH 7, 0.5 M) (4 : 6, v/v)].63 The complex

formation constant was calculated to be 1.24 � 105 M�1,

and selective UV absorption changes and fluorescence

quenching effects were observed due to the formation of

compound 37-I.

Boronic acids have been actively examined for the construction

of cyanide sensing systems. In most cases, the change from

electron deficient R–B(OH)2 to electron rich R–B�(CN)3 in

aqueous solutions at physiological pH can alter the color or

fluorescence properties of the probe. Geddes et al. reported

new pyridinium boronic acid derivatives 38a–c that serve as

fluorescent sensors for cyanide (Fig. 34).64 In the absence of

cyanide, intramolecular charge transfer (ICT) in these systems

occurs efficiently and the fluorophores in the probes are

effectively quenched. On the other hand, the extent of ICT

from the amino moiety to the pyridinium nitrogen is reduced

in the presence of cyanide, which was attributed to enhanced

electron donation from the cyanide-complexed boronic acid to

the quaternary nitrogen. The decrease in ICT enhances the

intensity of blue-shifted fluorescence. These three water-

soluble fluorescent probes have been used to determine the

free cyanide concentration at concentrations up to physio-

logically lethal levels of 40.5 ppm.

Recently, Tomapatanaget et al. reported acceptor–

donor–acceptor (A–D–A) systems (39a–c) composed of

naphthoquinone, imidazole and boronic acid moieties

(Fig. 35).65 The fluorescence band at 460 nm was switched

on upon the substitution of cyanide on the sensors in a

CTAB micelle. This was attributed to the ITC caused by

the poor acceptability on the boron center after cyanide

addition.

Fig. 29 (a) Structures of chromophores 32a and 32b. (b) Proposed

mechanism for the chemical reaction with cyanide.

Fig. 30 Structures of probes 33, 34a and 34b.

Fig. 31 Structures of receptor 35 and its adduct 35-I.

Fig. 32 Addition products of 36a and 36b with cyanide and fluoride,

respectively.

Fig. 33 Structures of receptor 37 and its adduct 37-I.


Application

The various sensors described in this review have potential

applications for the detection and quantification of cyanide in

real samples due to their detection limits being below the EPA

standard for drinking water. The capability of naked eye or

fluorescence detection strongly suggests that these sensors can

be used in kits for the detection of cyanide. A few reports have

already described systems that apply sensors to nano-

structured Al2O3 films,20 SAM,23 polymer backbones,24,25,52

QDs,26 and polymer films37/wool.57 These results suggest that

in the near future, various types of solid systems will be

configured to perform as sensitive and practical ‘‘dip-in’’

naked eye cyanide sensors.

Chemical analysis using portable microfluidic devices

enables environmental testing outside of the laboratory in a

low cost in situ manner.66 The nematode, which inhabits the

interstitial water between soil particles, is considered to be an

ideal organism for testing the cyanide toxicity of aquatic

media, such as municipal and industrial wastewater.67,68 Yoon

and Park et al. recently applied a microfluidic sensor system

they devised (Fig. 36a and b)29,43 to cell-imaging43 and in vivo

imaging of cyanide in Caenorhabditis elegans (Fig. 36c–e).29

The selective sensing of cyanide anions in water by using a

hybrid biomaterial composed of a mesoporous TiO2 film of

crystalline nanoparticles and the protein hemoglobin has also

been reported.69 Low levels of cyanide (o0.2 ppm) can be

detected by monitoring the absorption changes of the hybrid

biomolecular films upon cyanide binding to the heme groups.

Concluding remarks

This review covers recent reports describing cyanide sensing.

Attention has been given to approaches that involve hydrogen

bonding, displacement and nucleophilic addition, and

addition to boron. As described above, the nucleophilicity of

cyanide and the strong affinity of cyanide for Cu2+ and boron

are among the properties that have been used advantageously

in the design of selective cyanide probes. Considerable

attention has been focused on the development of cyanide

sensing systems in recent years. Therefore, it is likely that

various types of practical kits for monitoring drinking water

and industrial waste, or for detecting alarming biological

terror/warfare agents will soon be devised. In addition, the

design of new cyanide probes and the discovery of new

types of receptors for cyanide will contribute greatly to the

intellectual foundation of the anion recognition field.

Acknowledgements

This work was supported by the NRL program of

KOSEF/MEST (R04-2007-000-2007-0), the SRC program of

KOSEF/MEST (R11-2005-008-02001-0) and the WCU

program (R31-2008-000-10010-0). H. N. Kim thanks BK 21.

References

1 S. I. Baskin and T. G. Brewer, Medical Aspects of Chemical andBiological Warfare, ed. F. Sidell, E. T. Takafuji and D. R. Franz,TMM Publication, Washington, DC, 1997, ch. 10, pp. 271–286.

2 T. Suzuki, A. Hiolki and M. Kurahashi, Anal. Chim. Acta, 2003,476, 159.

3 A. Safavi, N. Maleki and H. R. Shahbaazi, Anal. Chim. Acta, 2004,503, 213.

4 D. Shan, C. Mousty and S. Cosnier, Anal. Chem., 2004, 76, 178.5 V. K. Rao, S. R. Suresh, N. B. S. N. Rao and P. Rajaram,Bull. Electrochem., 1997, 13, 327.

6 T. T. Christison and J. S. Rohrer, J. Chromatogr., A, 2007, 1155,31.

7 J. Yoon, S. K. Kim, N. J. Singh and K. S. Kim, Chem. Soc. Rev.,2006, 35, 355.

8 T. Gunnlaugsson, M. Glynn, G. M. Tocci, P. E. Kruger andF. M. Pfeffer, Coord. Chem. Rev., 2006, 250, 3094.

9 P. A. Gale, Acc. Chem. Res., 2006, 39, 465.10 R. Martınez-Manez and F. Sancanon, Chem. Rev., 2003, 103,

4419.11 S. K. Kim, D. H. Lee, J.-I. Hong and J. Yoon, Acc. Chem. Res.,

2009, 42, 23.12 H. N. Lee, Z. Xu, S. K. Kim, K. M. K. Swamy, Y. Kim, S.-J. Kim

and J. Yoon, J. Am. Chem. Soc., 2007, 129, 3828.13 D. G. Cho and J. L. Sessler, Chem. Soc. Rev., 2009, 38, 1647.14 G. J. Mohr, Anal. Bioanal. Chem., 2006, 386, 1201–1214.15 F. H. Zelder and C. Mannel-Croise, Chimia, 2009, 63, 58.16 K. W. Kulig, Cyanide Toxicity, U.S. Department of Health and

Human Services, Atlanta, GA, 1991.17 Guidelines for Drinking-Water Quality, World Health Organization,

Geneva, 1996.18 S.-S. Sun and A. J. Lees, Chem. Commun., 2000, 1687.19 P. Anzenbacher, Jr., D. S. Tyson, K. Jursıkova and F. N. Castellano,

J. Am. Chem. Soc., 2002, 124, 6232.

Fig. 34 Structures of probes 38a–c and mechanism of cyanide

addition to boronic acid adduct.

Fig. 35 Structures of receptors 39a–c and their adducts.

Fig. 36 Fluorescence images of 19 in the absence (a) and presence of

cyanide (b). Fluorescence images of the nematode C. elegans exposed

to sensor 8 only (c), with Cu2+ (d), with Cu2+ and cyanide (e).


20 N. Gimeno, X. Li, J. R. Durrant and R. Vilar, Chem.–Eur. J.,2008, 14, 3006.

21 Y.-H. Kim and J.-I. Hong, Chem. Commun., 2002, 512.22 H. Liu, X.-B. Shao, M.-X. Jia, X.-K. Jiang, Z.-T. Lia and

G.-J. Chen, Tetrahedron, 2005, 61, 8095.23 V. Ganesh, M. P. C. Sanz and J. C. Mareque-Rivas, Chem.

Commun., 2007, 5010.24 Q. Zeng, P. Cai, Z. Li, J. Qina and B. Z. Tang, Chem. Commun.,

2008, 1094.25 Z. Li, X. Lou, H. Yu, Z. Li and J. Qin, Macromolecules, 2008, 41,

7433.26 A. Touceda-Varela, E. I. Stevenson, J. A. Galve-Gasion, D. T. F.

Dryden and J. C. Mareque-Rivas, Chem. Commun., 2008, 1998.27 L. Shang, L. Zhang and S. Dong, Analyst, 2009, 134, 107.28 X. Lou, L. Zhang, J. Qin and Z. Li, Chem. Commun., 2008, 5848.29 S.-Y. Chung, S.-W. Nam, J. Lim, S. Park and J. Yoon, Chem.

Commun., 2009, 2866.30 F. H. Zelder, Inorg. Chem., 2008, 47, 1264.31 C. Mannel-Croise and F. Zelder, Inorg. Chem., 2009, 48, 1272.32 Y. K. Kim, Y.-H. Lee, H.-Y. Lee, M.-K. Kim, G. S. Cha and

K. H. Ahn, Org. Lett., 2003, 5, 4003.33 D.-S. Kim, H. Miyaji, B.-Y. Chang, S.-M. Park and K. H. Ahn,

Chem. Commun., 2006, 3314.34 Y. M. Chung, B. Raman, D.-S. Kim and K. H. Ahn, Chem.

Commun., 2006, 186.35 H. Miyaji, D.-S. Kim, B.-Y. Chang, E. Park, S.-M. Park and

K. H. Ahn, Chem. Commun., 2008, 753.36 H. Lee, Y. M. Chung and K. H. Ahn, Tetrahedron Lett., 2008, 49,

5544.37 Z. Ekmekci, M. D. Yilmaz and E. U. Akkaya, Org. Lett., 2008, 10,

461.38 H.-T. Niu, D. Su, X. Jiang, W. Yang, Z. Yin, J. He and

J.-P. Cheng, Org. Biomol. Chem., 2008, 6, 3038.39 H.-T. Niu, X. Jiang, J. He and J.-P. Cheng, Tetrahedron Lett.,

2008, 49, 6521.40 Y. Sun, G. Wang and W. Guo, Tetrahedron, 2009, 65, 3480.41 K.-S. Lee, J. T. Lee, J.-I. Hong and H.-J. Kim, Chem. Lett., 2007,

36, 816.42 K.-S. Lee, H.-J. Kim, G.-H. Kim, I. Shin and J.-I. Hong,

Org. Lett., 2008, 10, 49.43 S. K. Kwon, S. Kou, H. N. Kim, X. Chen, H. Hwang, S.-W. Nam,

S. H. Kim, K. M. K. Swamy, S. Park and J. Yoon, TetrahedronLett., 2008, 49, 4102.

44 Y. Chung, H. Lee and K. H. Ahn, J. Org. Chem., 2006, 71, 9470.

45 D.-G. Cho, J. H. Kim and J. L. Sessler, J. Am. Chem. Soc., 2008,130, 12163.

46 J. L. Sessler and D.-G. Cho, Org. Lett., 2008, 10, 73.47 C.-L. Chen, Y.-H. Chen, C.-Y. Chen and S.-S. Sun, Org. Lett.,

2006, 8, 5053.48 M. Tomasulo and F. M. Raymo, Org. Lett., 2005, 7, 4633.49 M. Tomasulo, S. Sortino, A. J. P. White and F. M. Raymo, J. Org.

Chem., 2006, 71, 744.50 J. Ren, W. Zhu and H. Tian, Talanta, 2008, 75, 760.51 S.-J. Hong, J. Yoo, S.-H. Kim, J. S. Kim, J. Yoon and C.-H. Lee,

Chem. Commun., 2009, 189.52 F. Garcıa, J. M. Garcıa, B. Garcıa-Acosta, R. Martınez-Manez,

F. Sancenon and J. Soto, Chem. Commun., 2005, 2790.53 Y.-K. Yang and J. Tae, Org. Lett., 2006, 8, 5721.54 J. V. Ros-Lis, R. Martınez-Manez and J. Soto, Chem. Commun.,

2002, 2248.55 X. Zhang, C. Li, X. Cheng, X. Wang and B. Zhang, Sens.

Actuators, B, 2008, 129, 152.56 A. Afkhami and N. Sarlak, Sens. Actuators, B, 2007, 122, 437.57 P. Kaur, D. Sareen, S. Kaur and K. Singh, Inorg. Chem. Commun.,

2009, 12, 272.58 G. Qian, X. Li and Z. Y. Wang, J. Mater. Chem., 2009, 19, 522.59 J. V. Ros-Lis, R. Martınez-Manez and J. Soto, Chem. Commun.,

2005, 5260.60 E. Palomares, M. V. Martınez-Dıaz, T. Torres and E. Coronado,

Adv. Funct. Mater., 2006, 16, 1166.61 J. O. Huh, Y. Do and M. H. Lee, Organometallics, 2008, 27, 1022.62 T. W. Hudnall and F. P. Gabbaı, J. Am. Chem. Soc., 2007, 129,

11978.63 T. Agou, M. Sekine, J. Kobayashi and T. Kawashima, Chem.–Eur.

J., 2009, 15, 5056.64 R. Badugu, J. R. Lakowicz and C. D. Geddes, J. Am. Chem. Soc.,

2005, 127, 3635.65 M. Jamkratoke, V. Ruangpornvisuti, G. Tumcharen, T. Tuntulani

and B. Tomapatanaget, J. Org. Chem., 2009, 74, 3919.66 S. Kou, H. N. Lee, D. v. Noort, K. M. K. Swamy, S. H. Kim,

J. H. Soh, K. Lee, S. Nam, J. Yoon and S. Park, Angew. Chem.,Int. Ed., 2008, 47, 872.

67 N. Tominaga, S. Kohra, T. Iguchi and K. Arizono, J. Health Sci.,2004, 50, 545.

68 X. Chen, S.-W. Nam, M. J. Jou, Y. Kim, S.-J. Kim, S. Park andJ. Yoon, Org. Lett., 2008, 10, 5235.

69 K. Poland, E. Topoglidis, J. R. Durrant and E. Palomares,Inorg. Chem. Commun., 2006, 9, 1239.


sensors for the optical detection of cyanide ion · sensors for the optical detection of cyanide...

Documents