fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions

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ISSN 0306-0012

0306-0012(2012)41:8;1-P

www.rsc.org/chemsocrev Volume 41 | Number 8 | 21 April 2012 | Pages 301334

Chemical Society Reviews

CRITICAL REVIEW

Ha Na Kim, Wen Xiu Ren, Jong Seung Kim and Juyoung YoonFluorescent and colorimetric sensors for detection of lead, cadmium,and mercury ions

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3210 Chem. Soc. Rev.,2012, 41, 32103244 This journal is c The Royal Society of Chemistry 2012

Cite this:Chem. Soc. Rev., 2012, 41, 32103244

Fluorescent and colorimetric sensors for detection of lead, cadmium, and

mercury ions

Ha Na Kim,wa Wen Xiu Ren,wb Jong Seung Kim*b and Juyoung Yoon*a

Received 8th September 2011

DOI: 10.1039/c1cs15245a

Exposure to even very low levels of lead, cadmium, and mercury ions is known to cause

neurological, reproductive, cardiovascular, and developmental disorders, which are more serious

problems for children particularly. Accordingly, great efforts have been devoted to the

development of fluorescent and colorimetric sensors, which can selectively detect lead, cadmium,

and mercury ions. In this critical review, the fluorescent and colorimetric sensors are classified

according to their receptors into several categories, including small molecule based sensors,calixarene based chemosensors, BODIPY based chemosensors, polymer based chemosensors,

DNA functionalized sensing systems, protein based sensing systems and nanoparticle based

sensing systems (197 references).

Introduction

Among various heavy metal ions, lead, cadmium, and mercury

ions are banned in electrical and electronic equipment by

the European Unions Restriction on Hazardous Substances

(RoHS) directive due to their hazardous nature.1 These three

heavy metal ions are not biodegradable, and hence can

accumulate in the environment, which results in contaminated

food and water.2 Therefore, World Health Organization

(WHO) and Environmental Protection Agency (EPA) have

strictly defined the concentration limits of these metal ions that

are allowed in the drinking water.3

Lead is the most abundant and toxic substance of the three, it

is often encountered in the environment due to its use in batteries,

gasoline, and pigments, etc.4 Lead pollution is a persisting

problem and a long-lasting danger to human health and the

environment, as the 300 million tons of lead mined to date are

still circulating mostly in soil and groundwater.5

Even very low

levels of lead exposure can cause neurological, reproductive,

cardiovascular, and developmental disorders, which introduce

particularly serious problems in children including slowed motor

responses, decreased IQs, and hypertension.6

Cadmium is also an extremely toxic and carcinogenic metal.7

A major exposure source is smoking and through food, but

inhalation of cadmium-containing dust is the most dangerous

route. Cadmium can be found in electroplated steel, pigments in

plastics, electric batteries and so on.8 A high exposure level of

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

b Department of Chemistry, Korea University, Seoul 130-701, Korea.E-mail: [email protected]; Fax: +82-2-3290-3121;Tel: +82-2-3290-3143

Ha Na Kim

Ha Na Kim was born in Seoul,

Korea, in 1980. She received

BS degree from Department

of Chemistry of Ewha Womans

University and obtained MS

degree in medical science from

Seoul National University in

2006. She is on a doctoral

course in Prof. Juyoung Yoons

laboratory in Ewha Womans

University.

Wen Xiu Ren

Wen Xiu Ren was born in

Changchun, China, in 1981.

In 2009, he obtained his PhD

from Kyungpook National

University under the supervi-

sion of Prof. Sang Chul Shim

and Prof. Chan Sik Cho. He

now works as a postdoctoral

fellow in Prof. Jong Seung

Kims laboratory at Korea

University.

w Contributed equally to this work.

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This journal is c The Royal Society of Chemistry 2012 Chem. Soc. Rev.,2012, 41, 32103244 3211

cadmium is associated with increased risks of cardiovascular

diseases, cancer mortality, and damage to liver and kidneys.9

Mercury is well known as one of the most toxic metals and is

widespread in air, water, and soil, generated by many sources

such as gold production, coal plants, thermometers, baro-

meters, caustic soda, and mercury lamps.10 As it can cause

strong damage to the central nervous system, accumulation of

mercury in the human body can lead to various cognitive and

motor disorders, and Minamata disease.11,12 A major absorp-

tion source is related to daily diet such as fish,13 and thus there

are considerable efforts contributed to the development of the

selective and sensitive detection methods.

Currently, the most common methods to detect heavy metal

ions include atomic absorption spectrometry,14 and induc-

tively coupled plasma mass spectrometry,15 however these

instrumentally intensive methods only measure the total metal

ion content, and often require extensive sample preparation.

Thus, a simple and an inexpensive method that not only

detects but also quantifies heavy metal ions is desirable for

real-time monitoring of environmental, biological, and indus-

trial samples.

Among various detection techniques, optical detections (via

fluorescence changes or colorimetric changes) are the most

convenient methods due to the simplicity and low detection

limit.1619 The most important advantage of a fluorescent

probe would be the intracellular detection. During the last

couple of decades, considerable efforts have been devoted to

the development of fluorescent and colorimetric sensors,

which can selectively detect metal ions.

To date there has been one review for lead analysis pub-

lished in 1998,20

this review is the first paper which system-

atically covers optical probes for lead, cadmium, and mercury

ions. Since Nolans and Lippard have reviewed the optical detec-

tion of mercury ions in 2008,21 we particularly focus on the recent

development of mercury detection between 2009 and 2011.

In this critical review, the fluorescent and colorimetric

sensors are classified according to their receptors into several

categories, including small molecule based sensors, calixarene

based chemosensors, polymer based chemosensors, DNA

functionalized sensing systems and nanoparticle based sensing

systems. Overall we would like to provide a general overview

of the design and application of Pb2+, Cd2+, and Hg2+

selective chemosensors.

Fluorescent and colorimetric sensors for detection of

lead ions

Chemosensors bearing heteroatom containing ligands

Small molecule based chemosensors. Czarnik and coworkers

reported a pioneering work regarding fluorescent chemo-

sensors for Pb2+ in 1996.22 Both 2- and 9-anthracene deriva-

tives bearing the N-methylthiohydroxamate ligand (1 and 2)

were prepared as shown in Fig. 1, which exhibited strongly

quenched fluorescence due to the photo-induced electron trans-

fer (PET). Complexation of 2-derivative1with Pb2+ resulted in

rapid metal ion-catalyzed hydrolysis. Whereas complexation

of 9-derivative 2 with Pb2+ induced a 13-fold fluorescence

enhancement at pH 9, which can be attributed to the steric

protection of the thiocarbonyl group by two peri hydrogens

(Fig. 1). Even though there were few competitive metal ions such

as Ag+, Co2+ and Hg2+, this is still one of the first examples of

fluorescent chemosensors for Pb2+.

Li et al. reported dibromo-p-methyl-methylsulfonazo

(DBM-MSA, 3) as a sensitive and selective chromogenic

Fig. 1 Structures of 2- and 9-anthracene derivatives (1and 2) and the

proposed binding mode of2 with Pb2+.

Jong Seung Kim

Jong Seung Kim was born in

Daejon, Korea, in 1963. He

received PhD from Department

of Chemistry and Biochemistry

at Texas Tech University. After

one-year postdoctoral fellow-ship at University of Houston,

he joined the faculty at Konyang

University in 1994 and trans-

ferred to Dankook University

in 2003. In 2007, he then moved

to Department of Chemistry at

Korea University in Seoul as a

Professor. To date, his research

records 270 scientific publica-

tions and 25 domestic and inter-

national patents.

Juyoung Yoon

Juyoung Yoon was born in

Pusan, Korea, in 1964. He

received his PhD (1994) from

The Ohio State University.

After completing postdoctoral

research at UCLA and atScripps Research Institute, he

joined the faculty at Silla

University in 1998. In 2002,

he moved to Ewha Womans

University, where he is currently

a Professor of Department of

Chemistry and Nano Science

and Department of Bioinspired

Science. His research interests

include investigations of fluores-

cent chemosensors, molecular

recognition and organo EL

materials.

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reagent for Pb2+ (Fig. 2).23 In 0.24 M phosphoric acid medium,

Pb2+ formed a 2 : 1 blue complex with 3, having a sensitive

absorption peak at 642 nm. Under optimal conditions, Beers

law was obeyed over the range 00.6 mg mL1 of Pb2+. The

lower limit of detection was found to be 2.21 ng mL1.

A similar approach was reported by Meng and coworkers.

A sensitive and selective chromogenic reagent dibromo-

p-methyl-carboxysulfonazo 4 (Fig. 2) was studied for the

spectrophotometric determination of Pb2+.24 In 0.25 M phos-

phoric acid medium, Pb2+

formed a 2 : 1 blue complex with4,having a sensitive absorption peak at 648 nm. Under optimal

conditions, Beers law was obeyed over the range from 0 to

0.8 mg mL1 of Pb2+ with a detection limit of 2.14 ng mL1. This

method was applied to determine the Pb2+ level in vegetables.

Compound5(Fig. 2) showed selective fluorescence enhance-

ment (lmax= 492 nm) with K+

in a mixed solution of CHCl3and CH3CN (9 : 1).

25 However, it was reported that the mixed

CH3CN/water solutions (510% H2O) of5 exhibited an even

larger fluorescence enhancement in the presence of Pb2+.

The emission intensity was increased by a factor of more than

20 and was accompanied by a shift in the emission maximum

from 486 to 498 nm. The Pb2+ complex with 5 formed a

unique structure involving a Pb2(CF3COO)4 unit sandwichedbetween two crown moieties of 5, which was confirmed by

X-ray crystallography.

Chen and Huang reported a new chemosensor 6 (Fig. 3),

which can signal Pb2+ selectively and improve the fluorescence

intensity in CH3CN.26 In fluorescence titration studies (lmaxfor

emission = 491 nm), 6 displayed 40-, 12-, and 18-fold fluores-

cence enhancements for Pb2+ (10 equiv.), Ba2+ (100 equiv.),

and Cu2+ (100 equiv.), respectively, due to the photo-induced

charge transfer (PCT) and metal binding-induced conforma-

tional restriction. As shown in Fig. 3, a 2 : 2 complex of Pb2+

and 6 was proposed since 6 had many advantages including

remarkable selectivity, much improved emission and easy detec-

tion. However, when the aqueous solution of Pb(ClO4)2 was

added to 6 in CH3CN, neither the binding strength nor the

fluorescence yield was affected.

In another study, Hayashitaet al.reported a supramolecular

7/g-cyclodextrin (g-CyD) complex sensor that exhibited the

monomer/dimer emission ratio response with high selectivity

for Pb2+

in 98% water/2% methanol (v/v) at pH 4.3 (Fig. 4).27

No obvious fluorescence was observed in the absence ofg-CyD.

In contrast, significant fluorescence emission appeared in the

presence of 12.0 mM g-CyD, indicating that 7 is dissolved inwater by forming an inclusion complex withg-CyD, which also

enhanced the fluorescence quantum yield. Upon the addition of

Pb2+, the broad emission observed in the longer wavelength

region (471 nm) intensified whereas the pyrene monomer emission

at 370410 nm decreased. The binding constant was calculated to

be 1.17 0.75 109 M2 with the stoichiometry of 2 : 1.

Kavallieratos et al. observed the efficient and selective ion-

exchange extraction of Pb2+

from water into 1,2-dichloroethane

(DCE) with concurrent fluorescence quenching using as an ion-

exchanger, the sulfonamide fluorophore8(Fig. 5).28 This simple

system did not require a secondary co-ligand in order to extract

Pb2+ and showed remarkable extraction selectivity against other

metals withDPb> 130DCuandDPb> 1400DZn. Fluorescencequenching was observed at 516 nm after the addition of

Pb(NO3)2 into a solution of8 and NH(i-Pr)2 in DCE. Specifi-

cally, the fluorescence intensity was reduced by as much as 29%

upon mixing 8 (10 mM) and NH(i-Pr)2 (22 mM) with 5.5 mM

Pb(NO3)2.

Two TTF-pyridyl derivatives9 and 10 (Fig. 5), in which the

TTF moiety and pyridyl group are linked by a double bond,

Fig. 2 Structures of compounds35.

Fig. 3 Structure of6 and its proposed 2 : 2 binding mode with Pb2+.

Fig. 4 Structures of 7 and g-CyD and the proposed binding mode

between 7/g-CyD with Pb2+.


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were studied as Pb2+ selective chemosensors in CH3CN.29 The

interaction between the pyridyl group and Pb2+ improves the

electron-accepting ability of the pyridyl group, which thus

induces the color change of the solution from yellow to deep

purple, the downfield shift of the proton peaks in 1H NMR,

and the increase of the oxidation potentials E1ox and E2ox to

more positive values. These dramatic changes were specific for

Pb2+. The stoichiometry for the9complex was 2 : 1 (9/Pb2+),

while that for the 10 complex was 1 : 1 (10/Pb2+) with the

binding constants (log Ks) of 5.42 and 5.57 for 9 and 10,

respectively.

a,b,g,d-Tetrakis(3,5-dibromo-2-hydroxylphenyl)porphyrin

(11) displayed the selective fluorescence quenching effect on

Pb2+ in the aqueous solution (pH 9.0) based on the chelation

of porphyrin by b-cyclodextrin (b-CD) as reported by Yang

et al. (Fig. 5).30 This caused a large increase of the porphyrin

fluorescence intensity (655 nm) and thus was sensitive to Pb2+

that displayed fluorescence quenching of11. The detection limit

of this system was in the concentration range of 2.8 107 to

7.4 105

M of Pb2+

. The organizing ability of the b-CD medium

and the protection of the ligand from the micro-environment

conferred increased sensitivity, selectivity and detection limit

compared with those obtained in the absence ofb-CD.

The Yoon group reported rhodamine B derivative 12 as a

fluorescent and colorimetric chemosensor for Pb2+ (Fig. 6).31

Among the various metal ions, compound 12 showed signifi-

cant fluorescent enhancement only with Pb2+ in CH3CN,

despite relatively small fluorescent enhancement with Cu2+

and Zn2+. From the fluorescent titrations, the association

constant for Pb2+

was calculated to be 1.95 105

M1. The

spiro-carbon in compound 12 appeared at d 64.7 ppm in

CD3CN : CDCl3 (9 : 1, v/v) and this peak disappeared upon

the addition of Pb2+ or Zn2+ which suggested a reversible

ring-opening mechanism as shown in Fig. 6.

Additionally, the Teramae group reported that the 13/Triton

X-100 complex (Fig. 7) formed below the critical micelle con-

centration (cmc) in water exhibited an amplified fluorescence

response for Pb2+.32 Dynamic light scattering and dark-field

microscope analyses revealed that the 13/Triton X-100 complex

formed pseudo-micelle aggregates, which was triggered by selec-

tive Pb2+

binding with13and resulted in improved fluorescence

intensity with a distinct blue shift of the fluorescence emission

at pH 5.70. The fluorescence color changed from green (lmax=

531 nm) to blue (lmax= 481 nm), which was easily confirmed

by the naked eye. The standard conditions used for fluores-

cence experiments employed 1.25 mM of13 in 0.4% 1,4-dioxane/

99.6% water (v/v) containing 0.08 mM Triton X-100 and

10.0 mM acetate buffer (pH 5.70).

The fluorescent sensor (14) containing the bis(2-pyridyl-

methyl)amine group as a binding moiety for Pb2+ was developed

by Hong and coworkers (Fig. 7).33

Compound 14 also showed

selective fluorescence intensity enhancement (lmaxfor emission =

562 nm) with Pb2+ over other metal ions in pH 7.0 HEPES

buffer solution. This was ascribed to the complex formation

between Pb2+ and14 that blocked the photo-induced electron

transfer process. A linear response as a function of Pb2+

concentration was obtained ranging between 1.9 107

and 6.0 106 M. The lower detection limit was found to

be 1.9 108 M (3.9 mg L1) which is below the maximal

allowed concentration of lead ions (10 mg L1) in drinking

water. Therefore, this indicated the great potential of14 to be

employed as the sensor material for Pb2+

detection.

A new type of synthetic fluorescent sensor 15 has been

studied for probing Pb2+ in living biological samples by the

Chang group (Fig. 7).34 Under simulated physiological con-

ditions (20 mM HEPES, buffer pH 7), a desirable selective

turn-on response for Pb2+ over competing metal ions was

observed. Kd for Pb2+ coordination to 15 was reported as

23 4mM. The addition of 15 ppb Pb2+, the maximum EPA

limit for the allowable level of lead in drinking water, to a 5 mM

solution of15 induced a 15 2% increase in the fluorescence

intensity. This fluorescent sensor 15 was hence successfully

applied to track the changes in Pb2+ levels within living cells.

Basuet al.have designed, synthesized, and characterized the

new turn-on ratiometric fluorescent lead sensor 16 (Fig. 8).35

Compound16 exhibited an absorption band at 415 nm and an

emission band at 465 nm. Upon incubation with lead acetate

solution, the absorption band shifted to 389 nm and the

emission band also shifted to 423 nm with a 5-fold increase

in the fluorescence intensity. Compound 16 was able to detect

Pb2+ in aqueous solution over a wide pH range (410) and

selectively in a mixture of several other metals at a concen-

tration as low as 10 ppb. This sensor is advantageous because

of its sensitivity for Pb2+ at concentrations below the limit

set by the US Environmental Protection Authority (EPA).

Additionally, the dissociation constant (Kd) of16 was calcu-

lated as 23 mM.

Guilard and coworkers reported a new colorimetric mole-

cular sensor based on a 1,8-diaminoanthraquinone signaling

subunit 17 (Fig. 8) as an efficient lead ion sensor in water atFig. 6 Structure of Pb2+ probe 12.

Fig. 7 Structures of1315 and Triton X-100.

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neutral pH for naked-eye detection.36 The addition of Pb2+

(1 equivalent) induced a dramatic change in color (from violet

to pink) that was blue-shifted by 47 nm and hence suggested a

strong binding of Pb2+ by the triamide 17. In addition, the

naked eye detection limit of Pb2+ was 23 ppm (1015 mM) in

solution, which can be improved to 21 ppb (0.1 mM) by using a

conventional spectrometer.

A fluoroionophore sensor,N-[4(1-pyrene)-butyroyl]-l-trypto-phan (18), was reported as a Pb2+ selective chemosensor by Wu

and colleagues (Fig. 8).37 In the aqueous solution, compound18

exhibited a very high sensitivity (0.15 mM) and the 18Pb2+

complex showed a selective excimer peak at 465 nm. Both

FT-infrared and Raman spectroscopy in addition to DFT

calculations were employed to predict a characteristic inter-

action of lead ions with two carboxylate groups and two

indole rings as well as the hydrogen bonding between two

amide groups with a stiochiometry of 2 : 1 (Pb2+

: 18).

Several years ago, a redox, chromogenic and fluorescent

chemosensor molecule based on a deazapurine ring 19 was

reported by Ta rraga and Molina et al. (Fig. 9).38 Upon the

addition of aqueous Pb2+

, compound19 in CH3CN showed aredox shift (DE1/2= 0.15 V of the Fe(II)/Fe(III) redox couple),

the colorless to orange color change and an emission change of

620-fold with a detection limit of 1.32 108 M. Compound

19 exhibited a very weak fluorescence in CH3CN at 364 and

377 nm and a large chelation-enhanced fluorescence (CHEF)

effect only with aqueous Pb2+

even though there was a relatively

small CHEF effect with Zn2+. From the fluorescence titrations,

the association constants (Ka) for Pb2+ and Zn2+ were calcu-

lated to be 6.1 105 and 2.7 104 M1, respectively.

The same group reported a series of ferrocenyl-containing

imidazopyridine and imidazophenazine receptors 2022 as

Pb2+ selective chemosensors (Fig. 9).39 Imidazophenazine-

ferrocene dyad 20 has also demonstrated its ability for Pb2+

sensing through redox (DE1/2 = 120 mV), absorption (Dl =

23 nm, pale orange to red color), and emission (CHEF = 133)

channels. The resulting Jobs plot suggested a 2 : 1 binding

model between 20 and Pb2+, with the association constant

being 3 108 M2 in CH3CN. The recognition properties of

the two-armed imidazopyridine-ferrocene triad 21 were very

similar to those exhibited by the parent monosubstituted

receptor 19, and the most salient features were a strong pertur-

bation of the redox wave (DE1/2 = 180 mV), the absorption

wavelength (Dl= 23 nm, colorless to yellow color), a dramatic

increase in the fluorescent quantum yield (Fcomplex/Fligand =

890) in the presence of Pb2+, while the optical responses toward

Zn2+

were silent. Binding assays using the continuous variation

method (Jobs plot) suggest a 1 : 1 binding model with a Ka=

1.4 105 M1. The two-armed imidazophenazine-ferrocene

triad 22 sensed Pb2+ through perturbation of the oxidation

potential of the Fe(II)/Fe(III) redox couple (DE1/2= 110 mV),

the important blue shift (Dl= 160 nm) of the high energy band

in the absorption spectrum, and a remarkable increase of the

emission band (CHEF = 220), whereas smaller changes were

observed in the presence of Zn2+. From the titration data, a

1 : 1 binding mode was deduced and the association constant

Ka was found to be 3.5 103

M1

for Pb2+

.

The synthesis and electrochemical, optical, and ion-sensing

properties of ferrocene-imidazophenazine dyads were also pre-

sented by Ta rraga and Molina et al.40 Compound 23 (Fig. 9)

behaved as a highly selective redox/chromogenic/fluorescent

chemosensor molecule for Pb2+ in CH3CN/H2O (9 : 1). The

emission spectrum illustrated a CHEF (47-fold) in the presence

of Pb2+, a new low-energy band appeared at 502 nm in its

UV/vis spectrum (yellow to orange color) and the oxidation

redox peak was anodically shifted (DE1/2 = 230 mV). From

the fluorescence binding isotherm, the association constant

was calculated to be 3.57 106

M1.

Calixarene based chemosensors

Quite a few examples of Pb2+ selective fluorescent chemo-

sensors utilized a unique calixarene template. Lerayet al.reported

a new fluorescent molecular sensor 24 based on a calix[4]arene

bearing four carboxydansyl groups as fluorophores (Fig. 10).41

The complexation of Pb2+ to 24 in the CH3CN/H2O system

induced a noticeable blue shift in the fluorescence spectrum and

an increase in the fluorescence intensity with an unprecedented

detection limit of 4 mg L1.

Kim and coworkers developed a series of calix[4]arene-based

fluorescent chemosensors for Pb2+ detection in the past few

years. In 2004, Kim and Lee et al. reported a new fluorescent

chemosensor with two different types of cation binding sites on

the lower rims of a 1,3-alternate calix[4]arene (25) (Fig. 11).42

Two pyrene moieties linked to a cation recognition unit that is

composed of two amide groups to form a strong excimer in



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solution. The excimer fluorescence can be quenched by the

addition of Pb2+ ions, and revived by further addition of K+

ions. Thus, metal ion exchange produced anOnOffOnswitch-

able fluorescent chemosensor. Computational results revealed

that the highest occupied molecular orbital (HOMO) and the

lowest unoccupied molecular orbital (LUMO) of the two

pyrene moieties interact under UV irradiation of 25 and its

K+ complex, while such HOMOLUMO interactions were

absent in the Pb2+ complex.

The Kim group also synthesized N-(1-pyrenylmethyl)

amide-appended cone calix[4]crown-5 (26) and its structuralanalogue crown-6 (27) (Fig. 12).43

Judging from the fluores-

cence changes upon the addition of cations, 27 having a

crown-6 ring displayed the higher Pb2+ ion selectivity over

other cations. Coordinating Pb2+ with two amide oxygen atoms

with the aid of a crown ring, a reverse PET occurred in such a

way that electrons transferred from the pyrene groups to the

electron deficient amide oxygen atoms resulting in a quenched

fluorescence. When diazo-phenyl units were modified to

compound27, new sensor 28 was formed which showed weak

fluorescence because of the energy transfer (ET) from the

pyrene groups to the electron deficient azo parts (Fig. 12).44

Upon the addition of Pb2+

, compound 28 revealed the

fluorescent and colorimetric dual changes, which arose from

a hypsochromic shift of the azo units in the UV spectrum as

well as the fluorescence enhancement of the pyrenyl parts

in the fluorescence spectrum via a suppressed fluorescence

resonance energy transfer (FRET).

Kim et al. also tried to replace the crown ring of 25 by a

triazacrown ring to give a new fluorescent chemosensor 29

(Fig. 13).45 When Pb2+ or Co2+ was bound to 29, both

monomer and excimer emissions quenched due to the combi-

nation of heavy metal effect, reverse-PET, and conformational

changes. The association constants (Ka) of 29 for Pb2+ and

Co2+ were 4.65 107 and 4.95 106 M1 in CH3CN,respectively. On the other hand, 29 illustrated the ability to

bind with anions, particularly F anions. Addition of F

anions to 29 formed a selective complex through H-bonding

and produced quenched monomer emission with little excimer

emission change due to the PET effect.

1,3-Alternate calix[4]arene 30 bearing bispyrenylamide on

the two lower rims and two carboxylic acids on the other two

lower rims was also synthesized by the Kim group (Fig. 14).46

When the Pb2+ ion was bound to two amide oxygen atoms

linked to pyrenylamide of30, it exhibited a marked quenched

excimer emission due to its geometrical change during the

complexation. This excimer emission band revived with

further addition of Ca2+ ions, indicating an interesting on/offswitch process.

As shown in Fig. 14, compound31 responded to K+, Pb2+,

or Cu2+ and revealed band shifting in both fluorescence and

absorption spectra with different binding modes.47 With K+,

fluorescence emissions of the ligand were barely affected, while

addition of Pb2+ or Cu2+ produced a remarkable change

in both excimer and monomer emissions. The observed data

indicated that the metal cation was encapsulated by the

crown-5 ring for K+ and by the two facing amide groups in

the latter case, which was verified by a metal ion exchange

experiment. The wavelength shifts in both fluorescence and

absorption spectra upon addition of Cu2+ showed that, in

Fig. 10 Structure of the fluorescent chemosensor 24.

Fig. 11 Structure of fluorescent chemosensor 25 and its proposedbinding models with Pb2+ and K+ ions.

Fig. 12 Structures of the fluorescent chemosensors26, 27 and 28.

Fig. 13 Structure of fluorescent chemosensor 29 and its proposed

binding models with Pb2+ and F ions.

Fig. 14 Structures of fluorescent chemosensors30 and 31.

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contrast to Pb2+, Cu2+ interacted with the nitrogen atoms of

the amide groups through the PCT mechanism.

In 2006, Kim and Vicens et al. designed an unsymmetrical

1,3-alternate calix[4]biscrown-based chemosensor 32 having

a 1,5-naphthalene unit (Fig. 15).48 The weak fluorescence

intensity of the naphthalene unit suggested that benzene rings

of the calix[4]arene as well as the oxygen atoms of the crown-5

ring take part in PET. Complexation of Pb2+ caused fluores-

cence quenching due to an inverse PET process. On the other

hand, binding of two K+ ions to both crown-5 and 1,5-

naphthalene-crown-6 loops of 32 induced the fluorescenceenhancement of the naphthalene unit by CHEF (chelation-

enhanced fluorescence).

Kim, No and Ham et al. reported the syntheses of C-1,2-

alternate homodioxacalix[4]arene pyreneamides 33 and 34

(Fig. 15). With metal ion complexation, their emission bands

and thermodynamic stabilities of the complexes were changed.49

Upon Pb2+

ion complexation, both 33 and 34 showed a

quenched fluorescence in both monomer and excimer bands.

Upon the addition of Ca2+ ions,33 gave no response while34

provided enhanced excimer and declined monomer emission

with ratiometric response. The excimer spectral changes were

rationalized by the frontier molecular orbital in that the

effective PyPy* interaction induced an emission intensityincrease upon Ca2+ ion complexation, while in contrast there

was no such interaction observed for Pb2+ binding.

1,3-Alternate calix[4]arene-based fluorescent chemosensor

35 containing two-photon absorbing chromophores was repor-

ted by Kim and Cho et al. (Fig. 16).50 The sensing behaviors of

35 toward metal ions were investigated via absorption band

shifts as well as one- and two-photon fluorescence changes.

Free ligands absorb light at 461 nm and weakly emit their

fluorescence at 600 nm when excited by UV-vis radiation

at 461 nm, without any two-photon excited fluorescence at

780 nm. Addition of Al3+ or Pb2+ ions to the ligand solution

caused the blue-shifted absorption and enhanced fluorescence

due to a declined resonance energy transfer (RET) upon

excitation by one- and two-photon processes. Addition of the

Pb2+ ion to a solution of35K+ resulted in a higher fluores-

cence intensity than the original35Pb2+ complex regardless of

the excitation pathway, due to the allosteric effect induced by

the complexation of K+ with a crown loop.

Huang and Chen et al. reported a new p-tert-butylcalix[4]-

arene-based chemosensor 36 with threeN,N-diethylacetamide

groups as the recognition site and one methyl 3-ethoxy-

naphthalene-2-carboxylate as the fluorescent group, which

exhibited a highly selective fluorescent response to Pb

2+

ions(Fig. 17).51 The association constant was 6.5 104 M1 in the

CH3CN/H2O system.

The Chung group reported a novel chromogenic calix[4]arene

sensor 37 bearing bistriazoles and azophenols as binding sites

and azo groups as signal transduction units, which displayed

selective coloration with Ca2+ and Pb2+ addition (Fig. 17).52

The association constants for the 1 : 1 complex of37 towards

Ca2+ and Pb2+ ions were determined to be 7.06 104 M1 and

8.57 103 M1, respectively, resulting in a large bathochromic

shift in the absorption spectrum.

Talanova et al.described a new, efficient, and highly selective

fluorescent chemosensor38bearing two pendent proton-ionizable

dansylcarboxamide groups to the calix[4]arene preorganized inthe partial cone conformation for determination of Pb

2+ions

(Fig. 17).53 Complexation of Pb2+ with38 induces a blue shift

as a result of the carboxydansyl fluorophore deprotonation. In

acidic CH3CN/H2O (1 : 1 v/v) solution, 38 allowed for the

detection of Pb2+ at the levels as low as 2.5 ppb.

New fluorescent sensors 3941 based on calix[4]arenes

have been synthesized by Kumar et al. (Fig. 18).54 Interaction

between Pb2+ ions and imino nitrogen of ligands causes

spectrofluorometric changes in the pyrenyl group because of

a reverse PET phenomenon. Compounds 39 and 40 in the

cone conformation showed ratiometric sensing while 41 with

the 1,3-alternate conformation exhibited OnOff signalling


Fig. 16 Structure of compound35.


Fig. 18 Structures of the fluorescent chemosensors3941.

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with Pb2+ ions. Compounds 40 and 41 also showed a colour

change from colourless to yellow upon the addition of

Pb2+ ions.

Peptide based chemosensors

Deo and Godwin reported a ratiometric fluorescent probe that

is selective for Pb2+.55 This probe consists of a fluorescent dye

(dimethylamino)-naphthalene-1-sulfonamide (dansyl or dns)conjugated to the amino terminus of a tetrapeptide (ECEE)

(glutamate, E, and cysteine, C). The specific amino acids

within the first generation ligand were chosen because their

side chains contain functional groups (carboxylates and thiols)

that are known to coordinate Pb2+ under biologically relevant

conditions. Upon addition of Pb2+, the emission maximum of

dns-ECEE shifts from 557 to 510 nm with the enhancement of

intensity. By plotting the ratio of fluorescence emission inten-

sity at 510 nm versus the fluorescence emission intensity at

557 nm (I510/I557), an EC50for Pb2+ was obtained asB120 mM.

Pb2+ induced hydrolysis

A fluorescent chemodosimeter 42 for Pb2+

was designed and

synthesized by linking resorufin (serving as a fluorophore and

electron acceptor) to p-nitrophenol (serving as a fluorescence

quencher and electron donor) through phosphodiester bonds

(Fig. 19).56 Upon the addition of Pb2+, the phosphate ester

bonds in the probe were cleaved and the fluorophore was

released, accompanying the retrievement of fluorescence.

Although the 5 h heating required for the reaction is its

primary shortcoming, it is directly proportional to the Pb2+

concentration in a range of 50125 nM with a detection limit

of 22 nM in phosphate buffer (pH 8).

Polymer based chemosensors

Compared to small organic compounds, polymer based optical

sensors displayed several important advantages.57 For instance,

signal amplification could be one of the most important

advantages.

Bunz and coworkers reported the simple polymer 43 as a

potent sensing platform for lead salts in the aqueous solution

(Fig. 20).58 The polymer has a strong emission at Imax= 465 nm,

typical for a dialkoxy-PPE. The fluorescence of an aqueous

PIPES-buffered solution (pH 7.2) of43 was efficiently quenched

by Pb2+ with aKSV= 8.8 105.43was by a factor of 1.5 103

more sensitive toward quenching than its model compound 44,

which can be attributed to multivalent binding that is an

important factor in the observed sensitivity.

A series of ethylene glycol (45), triethylene glycol (46) and

pentaethylene glycol (47) esters of 10,12-pentacosadiynoic acid

(PCDA) (Fig. 20) were synthesized by Sukwattanasinitt and

colleagues.59 Even though the glycol ester lipids could not

form polydiacetylenes upon UV irradiation, they however

could be mixed with PCDA up to 30 mol% and polymerized

to form blue sols. The PDA sols with blue to red colorimetricresponse selectively to Pb2+ offered a method for the naked

eye detection of Pb2+ at part per million levels. The color

transition was induced by the selective binding between Pb2+

and carboxylate groups of PCDA causing vesicle aggregation

and fusion. The dynamic range of47/PCDA (30/70 mol%) sol

for Pb2+

detection was determined by varying the concen-

tration of Pb(NO3)2 solution from 5 to 100 mM. Linear

colorimetric response was obtained with Pb2+ concentration

in the range of 530 mM.

Yoonet al. have developed a new PDA-based chemosensor

system for the detection of Pb2+ in the aqueous solution.60 UV

irradiation of the suspensions derived from both DA monomers

(48a: PCDA = 1 : 9) resulted in the formation of stable andblue-colored PDA molecules (48b) (Fig. 21). 48b (200 mM)

displayed a selective and clear blue-to-red transition only with

Pb2+ in HEPES (10 mM, pH 7.4) among various metal ions

tested, including Na+

, K+

, Ca2+

, Cd2+

, Co2+

, Cu2+

, Hg2+

,

Mg2+, Ni2+, Pb2+ and Zn2+. Since the blue-to-red transition

of the PDAs is accompanied by the generation of fluorescence,

the lead-promoted transition was also monitored by fluores-

cence spectroscopy.48b (50 mM) produced a large fluorescence

Fig. 19 Structure of the fluorescent chemodosimeter 42 and its two

possible hydrolytic routes.

Fig. 20 Structures of4347 and PCDA.

Fig. 21 Structure of monomer 48a and polymerization process of

polymer 48b.

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enhancement with Pb2+. The fluorescence spectra of the PDAs

48bshowed a gradual increase in the presence of 09mM Pb2+

with the detection limit of 0.8 ppm.

Pb2+-dependent DNAzyme based sensing systems

In 2000, Li and Lu reported a novel strategy to convert Pb2+

dependent DNAzyme (817 motif) into a highly selective and

sensitive fluorescence-based Pb2+ sensor.61 6-Carboxytetra-methylrhodamine (TMR) was labelled to the substrate (17DS)

containing a single RNA linkage (ribonucleoside adenosine,

(rA)) as a fluorophore. 4-(40-Dimethylaminophenylazo)benzoic

acid (Dabcyl) was labelled to the enzyme strand (17E-DY) as a

fluorescence quencher (Fig. 22(a)). When the substrate strand

was annealed to the enzyme strand, the TMR fluorescence was

quenched by nearby Dabcyl (Fig. 22(a)). Upon the addition of

Pb2+

, the fluorescence revived due to deoxyribozyme-catalyzed

cleavage of the substrate. The biosensor had a quantifiable detec-

tion range from 10 nM to 4 mM and a selectivity of >80-fold

for Pb2+ over other metal ions at 4 1C. In 2003, Lu and

co-workers optimized their sensing system by introducing

both inter- and intramolecular quenchers to overcome thetemperature limitation (Fig. 22(b)).62 More recently in 2009,

introduction of the mismatches into the DNAzyme to resist

temperature-dependent variations from 4 to 30 1C was explored

(Fig. 22(c)).63 The new sensor was designed with the GR-5

DNAzyme base instead of 8-17 DNAzyme which offered higher

selectivity and a slightly lower detection limit than previously

reported (Fig. 22(d)).64

Moreover, Tan and co-workers linked an 817 DNAzyme

sequence labelled with a quencher and a leaving substrate

fragment labelled with a fluorophore through a DNA hairpin

structure. This modification can bring the quencher in close

proximity to the fluorophore ensuring efficient fluorescence

quenching.65 The new probe showed a selectivity for Pb2+

over other metal ions, where the quantifiable detection range

was from 2 nM to 20 mM.

A similar work was reported by Zhanget al.66 The substrate

strand of the Pb2+-dependent DNAzyme was designed as

a molecular beacon (MB) for highly efficient quenching. Upon

the addition of Pb2+ ions, the DNAzyme catalyzed cleavage

of the MB substrate could convert the intramolecularly stable

hybridized MB stem into two much less stable intermolecularly

hybridized DNA strands, thereby releasing the fluorophore-

labeled DNA strand and finally generated a fluorescence signal

enhancement. The Pb2+ detection limit was 600 pM. In addi-

tion, this strategy is applicable to detect the adenosine with

similarly high sensitivity.

He et al. reported a fluorescent biosensor based on Pb2+-

regulatory protein in Ralstonia metallidurans CH34 with high

selectivity and sensitivity for Pb2+ ions.67 A 25-mer duplex

DNA containing the PbrR-binding sequence was prepared as

a probe (Fig. 23). In the central base pair of this sequence, a

fluorescent base, 2-aminopurine (2AP), was incorporated as

a messenger. Addition of Pb2+ ions and PbrR triggered a

distortion of the duplex DNA to generate an unpaired 2-AP

base, which would emit a strong fluorescence. At room tempera-

ture, the detection limit can reach the nanomolar range (50 nM)

for Pb2+

ions in solution. The probe was also highly selective

towards Pb2+ ions over other metal ions (about 1000-fold) and

could be reversed by the addition of ethylenediaminetetraacetate

(EDTA).

A new colorimetric and chemiluminescence detection system

for Pb2+ was reported by the Willner group.68 The probe was

constructed by hybridizing a nucleic acid containing Pb2+-

dependent cleaving DNAzyme and its substrate including

horseradish peroxidase (HRP)-mimicking DNAzyme. Upon

the addition of Pb2+ ions, the HRP-mimicking DNAzyme by

the cleavage of the substrate assembled in the presence of

hemin to a catalytic G-quadruplex. The catalytic G-quadruplex

catalyzed the H2O2-mediated oxidation of 2,20-azino-bis(3-

ethylbenzothiazoline)-6-sulfonate (ABTS2) or luminol, which

results in a color change or generates chemiluminescence (CL),

respectively. Furthermore, this method can be applied to

L-histidine detection by using L-histidine cofactor-dependent

nucleic acid cleaving DNAzyme instead of the Pb2+-dependent

cleaving DNAzyme.

Wang and Dong et al. designed another colorimetric and

CL sensor for Pb2+ based on a similar concept. In the presence

of K+

, a common G-quadruplex DNAzyme PS2.M (with

hemin as a cofactor) can effectively catalyze the H2O2-mediated

Fig. 22 Predicted secondary structures of the fluorescent DNAzyme

lead sensors and schematic representation of the catalytic beacon

sensor: (a) normal 817 DNAzyme sensor; (b) temperature independent

817 DNAzyme sensor; (c) 817 DNAzyme sensor with mismatches;

(d) GR-5 DNAzyme sensor. F represents the fluorophore, FAM, Q1 is

the quencher DABCYL and Q2 is the quencher BHQ-1s. The single

RNA base on the substrate arm is denoted by rA.

Fig. 23 Binding of Pb2+ ions to PbrR691 as revealed by a 2AP-

modified DNA probe. A# = 2-aminopurine = 2AP.

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oxidation of ABTS2 or luminol accompanied by color change

or CL emission, respectively (Fig. 24).69 Addition of the Pb2+

ion induced a conformational change in the K+-stabilized

PS2.M to Pb2+-stabilized structure which has a higher stability

and a lower DNAzyme activity than the former. Thus, this

system can be applied to colorimetric (ABTS2) and CL

(luminol) detection of Pb2+ in aqueous solution. In addition,

this sensing system provides good selectivity for Pb2+ with a

low detection limit (32 nM per ABTS2 and 1 nM per luminol).

The Chang group also developed a fluorescence approach

for Pb2+ ions detection based on another G-quadruplex

DNAzyme, AGRO100.70 In the presence of hemin, addition

of Pb2+ ions can increase DNAzyme activity of AGRO100 for

H2O2-mediated oxidation of Amplex UltraRed (AUR). The

AGRO100-AUR probe was highly sensitive (LOD = 0.4 nM)

and selective (by at least 100-fold over other metal ions)

toward Pb2+ ions, with a linear detection range from 0 to

1000 nM.

A thrombin-binding aptamer (TBA) labelled with a fluoro-

phore and a quencher was reported by Chang et al. as a

fluorescent sensor for Pb2+ and Hg2+.71 As shown in Fig. 25,

the TBA had a random coil structure that can be changed into

a G-quartet structure in the presence of Pb2+ and into a

hairpin-like structure in the presence of Hg2+ ions. Changes in

the DNA strands conformation caused fluorescence between

the fluorophore and the quencher to decrease via FRET. Pb2+

and Hg2+ ions can be selectively detected at concentrations as

low as 300 pM and 5.0 nM in the presence of phytic acid and a

random DNA/NaCN mixture, respectively.

Wang et al. reported a recoverable DNA molecular device

for the highly selective and sensitive fluorescent detection of

Pb2+ based on DNA duplexquadruplex exchange.72 T30695,

(GGGT)4, and its partly complementary strand were hybrid-

ized to form a DNA duplex. Addition of Pb2+ ions disrupted

the duplex and stabilized the newly formed G-quadruplex. The

Pb2+-stabilized G-quadruplex interacted with zinc proto-

porphyrin IX and enhanced its fluorescence intensity. Further

addition of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA), a strong Pb2+ chelator, can reset this

DNA molecular device.

Lu and Tong et al. developed a new label-free method

for fluorescent detection of Pb2+

ions.73

They introduced an

abasic site called dSpacer into the duplex regions of the 817

DNAzyme, which can bind to an extrinsic fluorescent com-

pound, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND),

and quench its fluorescence (Fig. 26). Addition of Pb2+ ions

enabled the DNAzyme to cleave its substrate and to release

ATMND from the DNA duplex, recovering its fluorescence.

Similarly, this method was also used for the fluorescent detec-

tion of adenosine by linking the dSpacer to the adenosine

aptamer. The adenosine-induced structural switching of theaptamer led to the release of ATMND and subsequent fluores-

cence enhancement. The detection limits of Pb2+ and adenosine

were 4 nM and 3.4 mM, respectively.

In 2010, the Lu group reported that DNA can hold ATMND

and quench its fluorescence by extending one end of DNA

with a loop to generate a vacant site (Fig. 27).74 Either metal

Fig. 24 Schematic of utilizing Pb2+-induced allosteric G-quadruplex

DNAzyme, PS2.M, for label-free colorimetric and CL detection of Pb2+.

Fig. 25 Representation of the sensing mechanism of the TBA probe

for the detection of Hg2+ and Pb2+ ions.

Fig. 26 Schematic illustration of label-free fluorescent detection of

(a) Pb2+ and (b) adenosine.

Fig. 27 Fluorescence enhancement response of the functional DNA

sensors specific to (a) Pb2+, (b) UO22+, (c) adenosine, and (d) Hg2+

using unmodified DNA via a vacant site.

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ion-dependent cleavage by DNAzymes or analyte-dependent

structural-switching by aptamers could release ATMND from

the DNA duplex and recover its fluorescence. As shown in

Fig. 27, label-free fluorescent sensors for Pb2+, UO22+, Hg2+,

and adenosine were developed with high selectivity and sensi-

tivity. The detection limits decreased to 3 nM, 8 nM, 30 nM,

and 6mM for UO22+

, Pb2+

, Hg2+

and adenosine, respectively.

Recently, Liu and Lu reported highly sensitive and selective

colorimetric sensing systems for Pb2+ detection by using

Pb2+-dependent DNAzyme as a target recognition element

and DNA-functionalized gold nanoparticles as a signaling

element.7578 As shown in Fig. 28, the Pb2+-dependent DNA-

zyme was composed of an enzyme (17E) and a substrate strand

(17DS) which was extended on both ends. Hybridization of

the substrate with DNA attached nanoparticles induced

aggregation of nanoparticles to provide a color change from

red to blue.75 In addition, the nanoparticles could be aligned

either in a head-to-tail manner or in a tail-to-tail manner

according to the DNAs attached to the nanoparticles. In the

former case, heating-and-cooling process (annealing) was

required for the aggregation.76,77 However, in the presence

of Pb2+, the substrate was cleaved by the enzyme, which inhibits

the aggregation, and hence the color remains red. Furthermore,

for the tail-to-tail aligned nanoparticles, the aggregation can be

perturbed by further addition of Pb2+ to result in a blue-to-red

color change, whereas the head-to-tail manner cannot.78 This

process could be accelerated by using small pieces of DNA to

invade the cleaved substrate of the DNAzyme.

In 2008, Lu et al. reported a simple label-free colorimetric

sensor for on-site and real-time Pb2+ detection.79 In the absence

of Pb2+, the salt-induced aggregation of gold nanoparticles

resulted in a color change from red to blue. This aggregation

could be prevented by single-stranded DNA, which was released

from the enzyme-complex by Pb2+ induced cleavage. The sensor

exhibited a low detection limit of 3 nM and higher selectivity for

Pb2+ over other metal ions.

Nanoparticle based sensing systems

Hupp et al. reported a simple colorimetric technique for the

detection of aqueous heavy metal ions, such as Pb2+, Cd2+,

and Hg2+. 13.6 0.4 nm diameter gold particles capped with

11-mercaptoundecanoic acid (MUA) were employed as

chromophores (Fig. 29).80 Functionalized gold nanoparticles

were aggregated in solution in the presence of divalent metal

ions by an ion-templated chelation process as shown in Fig. 33,which induced an easily measurable change in the absorption

spectrum of the particles. The aggregation also enhanced the

hyper-Rayleigh scattering (HRS) response from the nanoparticle

solutions, providing an inherently more sensitive method of

detection. The chelation/aggregation process was reversible via

the addition of a strong metal ion chelator such as EDTA.

Thomas and colleagues reported Au and Ag nanoparticles

that can be employed as Pb2+ selective colorimetric sensors,

prepared by mixing the corresponding metal cations (Au3+ or

Ag+) and a naturally occurring bifunctional molecule, gallic

acid (Fig. 30).81 This system is known for its ability to detect

micromolar quantities (ppm level) of Pb2+ ions even in the

presence of other metal cations in water resulting in a visualcolor change from pink to blue for Au nanoparticles and

yellow to red for Ag nanoparticles. Detailed mechanistic

investigations indicated that the hydroxyl group of gallic acid

(Fig. 30) is involved in the reduction of the Au 3+/Ag+ ions

and that the carboxylate group binds strongly to the surface of

the nanoparticles. The newly synthesized nanoparticles are

extremely stable in the pH range between 4.55.0. Under these

pH conditions, it is difficult to bring nanoparticles in proximity

due to strong interparticle electrostatic repulsion. However,

the unique coordination behavior of Pb2+ ions (coordination

number up to 12 with flexible bond length and geometry)

allows the formation of a stable supramolecular complex

resulting in the plasmon coupling and a visual color change.

Fig. 28 (a) Secondary structure of the DNAzyme. (b) Cleavage of

17DS by 17E in the presence of Pb2+. Pb2+-directed assembly of gold

nanoparticles by the DNAzyme when nanoparticles are aligned in a

head-to-tail (c) or a tail-to-tail manner (d). (e) For head-to-tail aligned

aggregates, Pb2+ cannot induce DNAzyme cleavage and no color change

can be observed. (f) For tail-to-tail aligned aggregates, Pb2+ can induce

DNAzyme cleavage and color change can be observed. The rate of color

change can be significantly increased by adding invasive DNA.

Fig. 29 Proposed process for the metal ion induced aggregation of

Au-MUA.

Fig. 30 A general scheme for two electron oxidation of gallic acid to the

corresponding quinine form and a representation of electrostatic inter-

action of carboxylic groups on the nanoparticle surface and the hydrogen

bonding network formed between the surface capped molecules.

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Positively charged CdTe-QDs capped with cysteamine

(CA-CdTe-QDs) and negatively charged AuNPs capped with

11-mercaptoundecanoic acid (MUA-AuNPs) (Fig. 31) havebeen prepared and used for the determination of Pb2+ by

Wang and Guo.82 These positively charged CACdTe-QDs

formed FRET donoracceptor assemblies with negatively

charged MUA-AuNPs due to electrostatic interactions, which

effectively quenched the PL intensity of the QDs (Fig. 31). A

novel inhibition assay method for Pb2+ detection was proposed

based on the modulation effect of Pb2+ on the FRET efficiency

between QDs and AuNPs (Fig. 31). The response was linearly

proportional to the concentration of Pb2+ in the range of

0.224.51 ppm, and the detection limit was calculated to be

30 ppb of Pb2+.

Meanwhile, Huang and colleagues developed a colorimetric,

label-free gold nanoparticle (Au NP) probe for the detectionof Pb2+ in aqueous solution.83 The unique feature here is that

this system is a nonaggregation-based nanoparticle sensor, in

which Pb2+ ions accelerate the leaching rate of Au NPs by

thiosulfate (S2O32) and 2-mercaptoethanol (2-ME) (Fig. 32).

The formation of PbAu alloys accelerated the Au NPs rapid

dissolution into solution, leading to dramatic decreases in

the surface plasmon resonance (SPR) absorption. The 2-ME/

S2O32-Au NP probe was highly sensitive (LOD = 0.5 nM)

and selective (by at least 1000-fold over other metal ions)

toward Pb2+ ions, with a linear detection range (2.5 nM10 mM).

Glutathione functionalized gold nanoparticles (GSH-GNPs)

were reported by Suet al.as a facile, cost-effective and sensitive

colorimetric detection method for Pb2+

(Fig. 33)84

which canpotentially induce immediate aggregation of these nanoparticles.

Therefore the existence of Pb2+ was able to be detected by

colorimetric response of GNPs monitored from a UV-vis

spectrophotometer or even with the naked eye (red to blue color

change), and the detection limit had the potential to reach

100 nM. The SPR of the GSH-GNPs solution at 700 and

520 nm are related to the quantities of dispersed and aggregated

GSH-GNPs, respectively.

Alkanethiol-bearing monoazacrown ethers were also used to

modify gold nanoparticles (AuNPs) as a simple and fast colori-

metric sensor to selectively detect Pb2+ in aqueous solutions(Fig. 34).85 These AuNPs selectively sensed Pb2+ through color

change from brown to purple, which was visually discernible by

an appearance of the surface plasmon band (SPB) at 520 nm.

The recognition mechanism is attributed to the unique structure

of the monoazacrown ether attached to AuNPs and the metal

sandwich coordination between two azacrown ether moieties

that are attached to separate the nanoparticles.

Han et al. adopted 11-mercaptoundecyl phosphoric acid as

a thiol ligand for AuNPs (Phos-AuNPs) based on the fact

that alkyl phosphates are potentially good ligands for Pb2+

because Pb2+ easily forms solids with phosphates and approxi-

mately 95% of the body burden of lead is stored in the bones as

lead phosphate derivatives.86 Phos-AuNPs were aggregatedby Pb2+, which caused a dramatic red-to-blue color change.

The detection limit of Phos-AuNPs for Pb2+ was reported as

1.637mM from the titration results.

Functional materials based sensing systems

In 2007, the Crego-Calama group developed a new sensing

material for the detection of heavy metal ions.87 The arrays

of 21 different fluorescent sensing monolayers, which were

consisted of 3 different fluorophores and 7 different ligands,

were directly generated by combinatorial methods and immo-

bilized on the wells surface of glass microtiter plates (Fig. 35).

Fig. 31 (a) Schematic representation of the FRET donoracceptor

assembly of positively charged CA-CdTe-QDs and negatively charged

MUA-AuNPs; (b) schematic representation of the inhibition assay

method for Pb2+ determination.

Fig. 32 Sensing mechanism of the 2-ME/S2O32-Au NP probe for

the detection of Pb2+ ions.

Fig. 33 Strategy for the colorimetric detection of Pb

2+

using GSH-GNPs.

Fig. 34 Schematic representation of the Pb2+-induced aggregationvia

sandwich complexation of azacrown ether-capped gold nanoparticles.

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Upon the addition of metal ions, such as Cu2+, Co2+, Pb2+,

Ca2+ and Zn2+, the monolayers produced various responses

by low selective interactions. These responses could be collected

by laser confocal microscopy and microarray reader fluores-

cence scanner and processed for each analyte as the charac-

teristic fluorescent pattern. The sensing systems can be recovered

by washing with EDTA solution.

As shown in Fig. 36, Asher and coworkers prepared two-

dimensional (2-D) polystyrene particle arrays with a high

diffraction ratio of incident light.88 These 2-D particle arrays

can be immobilized on hydrogel thin films containing different

molecular recognition agents for chemical sensing by polymer-

ization. In the presence of a special analyte, 2-D lattice spacing

of the arrays can be changed by hydrogel swelling/shrinking

caused by analyte-induced alterations of hydrogel osmotic

pressure, resulting in changes in the diffracted wavelength.

When acrylic acid (AAc) was copolymerized, the sensing

system showed high pH dependence in a range of pH 3.22 to

7.91. Furthermore, copolymerization of 4-acryloylamido-

benzo-18-crown-6 (4AB18C6) into the hydrogel produced a new

sensing material which can detect less than 1012 mol of Pb2+.

Fluorescent and colorimetric sensors for detection ofcadmium ions

Small molecule based chemosensors

In 2001, Prodi and Savage et al. designed and synthesized

5-chloro-8-methoxyquinoline appended diaza-18-crown-6 (49)

(Fig. 37) as a chemosensor for Cd2+ detection.89 Compound

49 exhibited extremely weak emission in methanol solution.

The crown ring moiety can bind to various metal ions,

including alkali and alkaline earth but with the exceptions of

Mg2+, transition and post-transition metal ions. Among them

only Cd2+

and Zn2+

could bind with49and give about 30 nm

red shift of lem with high quantum yield. In addition, the

enhancement factor for Cd2+

(94-fold) is larger than for Zn2+

(69-fold).

Three mixed donor phenanthroline-containing macrocycles

(5052) (Fig. 38) as fluorometric chemosensors for toxic heavy

metal ions were reported by Lippolis and coworkers.90 These

macrocycles could interact with Pb2+, Cd2+, and Hg2+ to

generate different complex species depending on the molar

ratios of M/L. In CH3CN solution, addition of Pb2+ and

Hg2+

induced a chelation enhancement of fluorescence

quenching (CHEQ) for all three ligands. In contrast, upon

addition of Cd2+, the CHEQ effect could be observed with 50

and 52 in the low molar ratio range (Cd2+/50 o 1; Cd2+/

52 o 0.5), and then the CHEF occurred in the higher molar

ratios range (1 o Cd2+

/50 o 2; 0.5 o Cd2+

/52 o 1). For51,the Cd2+ induced CHEF effect occurred in the whole range of

molar ratios.

Yoon et al. synthesized two anthracene derivatives bearing

the iminomethyl diacetic acid moiety at 9,10-(53) and 1,8-

positions (54) for selective fluorescent cadmium chemosensors

(Fig. 39). Fluorescence studies of53 indicated a selective and

Fig. 35 (a) The self-assembled monolayers formed in each well of the

glass microtiter plate (MTP); (b) the arrays of 21 different fluorescent

sensing monolayers (TM0-TM6, T0-T6, L0-L6) in MTP. (c) Chemical

composition of each fluorescent sensing monolayer.

Fig. 36 Fabrication of a 2-D photonic crystal for sensing

applications.

Fig. 37 Structure of compound 49 and its proposed binding mode

with Cd2+.


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large CHEF effect by a PET mechanism with Cd2+

at pH 10,

0.1 M CAPS buffer, even though there was a relatively small

CHEF effect with Zn2+.91 The association constants for Cd2+

and Zn2+ were calculated to be 69100 and 3200 M1,

respectively. The stoichiometry with Cd2+ was 1 : 1 binding

and the selectivity for Cd2+ was 20 times larger than that for

Zn2+. In 100% aqueous solution,54 was heavily quenched by

metal ions via PET.92 Particularly, the Cd2+54 complex

displayed a unique red-shifted broad band due to the chelato-

selective fluorescence perturbation resulted from electrophilic

aromatic cadmiation.

Gunnlaugsson et al.reported compounds55and56 (Fig. 39)

as fluorometric chemosensors for Cd2+ based on the PET

principle, using an anthracene fluorophore, connected to either

one or two iminodiacetate receptors by a methylene spacer.93

Both 55 and 56 have good water solubility and are pH-

independent in the physiological pH range. Upon addition of

Cd2+, the formation of charge-transfer complexes (exciplexes)

induced fluorescent enhancement atlmax= 506 and 500 nm for

55 and 56, respectively, whereas addition of Zn2+ only causes

the increase of (monomeric) anthracene emission of 56 and a

red-shifted emission (lmax= 468 nm) of55. Thus, both55 and

56 demonstrated sufficient Cd2+ selectivity over Zn2+ under

physiological conditions.

Compound57 (Fig. 40), a di-substituted bis(anthrylmethyl)

derivative of 1,8-dimethylcyclam, was studied by Youn and

Chang as a Hg2+- and Cd2+-selective fluorogenic sensor in

aqueous CH3CN solution.94 The water content of the aqueous

CH3CN solution can dominate the signaling type of the

recognition of Hg2+ and Cd2+. An OFFON type signaling

was observed for Hg2+ and Cd2+ ions in low water content

solutions (CH3CN : H2O = 90 : 10, v/v), while a selective

ONOFF type signaling toward Hg2+ ions was observed in

50% aqueous CH3CN solution.

Noveron and Stang et al. developed a new chromogenic

phenanthroline-containing supramolecular optical sensor (58)

(Fig. 41) for transition metals such as Ni2+, Cd2+, and

Cr3+.95 The 1 : 1 complexations of58 with Ni2+, Cd2+, and

Cr3+ in methanol solution induced dramatic changes in the

UV-vis spectrum. The binding constants are calculated to be

2.01 0.05 107 M1, 3.39 0.5 104 M1 and 7.53 0.4

103 M1 for Ni2+, Cd2+, and Cr3+, respectively.

Yuasa and coworkers designed and synthesized a carbohydrate-based fluorometric chemosensor (59) (Fig. 42) for Zn2+ and

Cd2+.96 Two amino groups stayed at the 3 and 5 positions of

the carbohydrate component as the recognition group and

two pyrene groups were attached to 2 and 4 positions as the

fluorophore. In the absence of metal ions, the two pyrene

groups were separated apart from each other and therefore

only produced monomer emission. Addition of metal ions

induced ring flip of the carbohydrate that led the pyrene

groups to fold and thus to afford excimer emission. Overall,

59also achieved high selectivity for Zn2+ and Cd2+ over other

metal ions in acetone solution.

Zhang and Yu et al. reported the design and synthesis of a

porphyrin-appended terpyridine (60) (Fig. 43) as a fluorometric

chemosensor for recognition of Cd2+ ions.97 Upon addition of




with Cd2+.


with M2+.


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This new b-cyclodextrin derivative 88 (Fig. 55) showed very

weak fluorescence because of the intramolecular PET from N

atom in the triazole moiety to the 8-hydroxyquinoline fluoro-

phore. Addition of Cd2+ can recover the fluorescence by

inhibiting the PET process. The Jobs plot analysis suggested

a 1 : 1 stoichiometry of88/Cd2+ complex. Moreover, the limit

of detection (LOD) for88towards Cd2+

was found to be 1.89

103

M. In addition, using sodium adamantine carboxylate as a

co-chelating agent, the binding constant (log Ks) increased from

2.10 0.23 to 3.38 0.09 without affecting the emission

wavelength.

A new fluorescent Cd2+ sensor (89) (Fig. 56) based on

8-hydroxyquinoline containing a 2,8-dithia-5-aza-2,6-pyridino-

phane as an ionophore has been synthesized.118 This chemo-

sensor exhibited a significant CHEF response toward Cd2+ not

only in aqueous solutions but also in sodium dodecyl sulfate

micelles, liposomes, and living cells. The 1 : 1 stoichiometry of

89Cd2+

complex was confirmed by X-ray structure analysis.

Probe 89 was proved to be a good choice for selective imaging

of Cd2+ in living cells owing to its low cytotoxicity and low

background fluorescence.

Li and coworkers reported dipyrrolylquinoxaline (DPQ)

derivatives 90 and 91 as new fluorescent sensors for transition-

metal ions.119 Both 90 and 91 showed good sensitivity toward

Cd2+, Zn2+ with turn-on fluorescence based on the CHEF

mechanism and Cu2+, Hg2+ turn-off fluorescence based on the

CHEQ mechanism. Jobs plot and crystal structure analysis

indicated the formation of M90 (or 91) complex with 1 : 1

stoichiometry.

Compound 92 (Fig. 57), containing a benzoimidazole

moiety as a fluorophore and DPA as an ionophore, was reported

as a ratiometric fluorescent Cd2+ sensor by Guo and Heet al.120

In the HEPES buffer solution (50 mM, 0.1 M KNO3, pH 7.2)

of 92, addition of Cd2+ led to the co-planation of pyridine

and benzoimidazole moieties and also enhanced electron-

withdrawing ability of the acceptor resulting in both absorp-

tion spectra (red shift about 19 nm) and emission spectra

changes (red shift about 53 nm). UV-vis and fluorescence

titrations indicated the 1 : 1 binding stoichiometry of92Cd2+

complex with picomolar sensitivity. Metal-ion selectivity experi-

ments indicated that probe 92 was unaffected by other metal

ions, except Zn2+

. Although Zn2+

addition also induced a red

shift in emission, it has little disturbance to the Cd2+ detection.

Probe 92 also exhibited high cell membrane permeability and good

reversibility with the metal ion chelator TPEN in HeLa cells.

Yoon and co-workers designed a naphthalimide-based

fluorescent chemosensor 93 for ratiometric Zn2+ and Cd2+

detection (Fig. 58).121 Large fluorescent enhancements were

observed upon addition of Zn2+ (22-fold) and Cd2+ (21-fold).

Notably Cd2+ induced a blue shift to 446 nm (blue fluorescence),

while Zn2+ caused a red shift to 514 nm (green fluorescence) in

the aqueous solution (CH3CN/0.5 M HEPES (pH 7.4) = 50 : 50)

via amide tautomerization. The colorimetric changes could

be distinguished by the naked eye and also Jobs plot study

illustrated the 1 : 1 binding mode of 93Cd2+ and 93Zn2+

complexes.

In 2011, Qian and Xu et al. investigated two near-infrared

fluorescent sensors 94 and 95 (Fig. 58) based on a tricarbo-

cyanine fluorophore for detecting Cd2+.122 Both 94 and 95

showed high selectivity and sensitivity to Cd2+ over other

metal ions, in particular95, which can even distinguish Cd2+

in Tris-HCl (12.5 mM) solution (containing 0.05 mM sodium


Fig. 55 Structure of compound 88 and its proposed binding modes

with Cd2+ and sodium adamantane carboxylate.

Fig. 56 Structures of compounds89, 90 and 91.

Fig. 57 Structure of92 and its binding mode with Cd2+.

Fig. 58 Structures of compounds93, 94 and 95.

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Shiet al.described the complexation of cationic 5,10,15,20-

tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP) and negatively

charged chemically converted graphene (CCG) sheets and utilized

the TMPyP/CCG complex (Fig. 62) as an optical sensor for

detecting Cd2+ ions in aqueous media.129 Addition of Cd2+

ions to the pure TMPyP solution exhibited a bathochromic

shift of absorption band (ca.22 nm). In the presence of CCG,

the chelating reaction between TMPyP and Cd2+ ions was

greatly accelerated from 20 h to 8 min under ambient condi-

tions with a larger bathochromic shift (ca.40 nm). Overall, the

TMPyP/CCG complex displayed high selectivity towards

Cd2+ ions over other metal ions, including Zn2+ ions.

The design and synthesis of triazole-ester modified silver

nanoparticles (TE-Ag NPs) (Fig. 63) was reported by the Li

group.130 TE-Ag NPs showed high selectivity towards Cd2+

over other metal ions. Addition of Cd2+ ions into TE-Ag NPs

solution induced a dramatic increase of the absorbance intensity

at 550 nm resulting in a significant color change from yellow to

red, which can be observed by the naked eye. The TEM image

indicated that the color change of TE-Ag NPs in the presence of

Cd2+ is attributed to the Cd2+-induced assembly of TE-Ag NPs.

The limit of colorimetric detection for Cd2+ is 2.0 105 M.

Anzenbacher, Jr.et al.reported a fluorescence sensor array,

which was generated by dispersing 9 cross-reactive sensors

(S1S9) (Fig. 64) in a hydrophilic polyurethane carrier.131

Based on the various affinities and selectivities of the sensors,

this array can distinguish metal cations, such as Ca2+, Mg2+,

Cd2+, Hg2+, Co2+, Zn2+, Cu2+, Ni2+, Al3+, Ga3+ at

different ranges of pH and at different cation concentrations

using linear discriminant analysis (LDA). This array was also

used to identify samples from nine different mineral water

brands without any pretreatment.

Based on a similar concept, Feng and Guanet al.reported a

solgel membrane array, which immobilized five commercially

available colorimetric indicators (Fig. 65) for the discrimina-

tion of trace heavy metal ions.132

Color-difference maps weregenerated by comparing the digital red, green, and blue values

in the presence and absence of analytes. Using this array, eight

heavy metal ions, including Pb2+, Hg2+ and Cd2+, can be

differentiated at standard concentrations of wastewater discharge.

Fluorescent and colorimetric sensors for detection of

mercury ions

Small molecule based chemosensors

Ferrocene based small molecules.Ta rraga and Molina et al.

reported ferrocene-based multichannel molecular chemosensors

Fig. 62 Structure of the TMPyP/CCG complex.

Fig. 63 Structure of TE-Ag NPs.

Fig. 64 Structures of the chemosensors S1S9 used in the array.

Fig. 65 Structures of five indicators and color-difference maps of eight

heavy-metal ions at standard concentrations of wastewater discharge.

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bearing two pyridine rings which have Hg2+ selectivity through

three different channels: the oxidation peak that is anodically

higher shifted (DE1/2= 300 mV for 97 and DE1/2 = 200 mV

for 98), new low-energy bands that appear in the absorption

spectrum at 483 nm and 485 nm, respectively. Also, the

emission bands of 97 and 98 were red-shifted by 28 nm and

32 nm, respectively. Remarkable chelation-enhanced fluores-

cent factors (CHEF = 227 for 97 and 165 for 98) were

accompanied. The changes of compound 97 in absorption

spectra are accompanied by the color change from yellow to

orange, which allows the potential naked eye detection.40,133

The P. Ghosh group reported thiomethoxychalcone-based

ligands99 and 100 as Hg2+ selective chemodosimeters. In the

acetonitrile solution, these two compounds showed selective

color changes from orange to purple with Hg2+, and the UV/vis

titration results indicated the formation of 2 : 1 (99: Hg2+) and

1 : 1 (100: Hg2+) complexes. X-ray crystal structure and cyclic

voltammetric studies supported a selective chemodosimetric

desulfurization between Hg2+ and99 or 100.134

Kim et al. developed a ferrocene-based electrochemical

chemodosimeter for Hg2+ recognition.135 Addition of Hg2+

induced cyclization and desulfurization as shown in Fig. 66. In

addition, an anodic shift of 101s redox potential and a red

shift in UV-vis spectroscopy were observed in CH3CN/H2O

(9 : 1) solution with high selectivity among the various metal ions.

Rhodamine based small molecules. Three sensors bearing the

thiophene group and rhodamine, or thiospirolactam rhodamine,

were synthesized for the selective detection of Hg2+ by Duan

et al.136 Compared to compounds 102 and 103, compound 104

containing two rhodamine carbohydrazone arms exhibited better

selectivity for Hg2+ in fluorescent enhancement and absorption

detection (Fig. 67). The ppb level fluorescent detection limit of

102,103and104for Hg2+ offered their potential applications in

the Hg2+ detection of drinking water.

Recently, Yoon et al. described two rhodamine hydrazone

derivatives bearing a thiol (105) and a carboxylic acid group

(106) as selective fluorescent and colorimetric chemosensors

for Hg2+ (Fig. 68).137 Both the chemosensor samples containing

Hg2+ in aqueous solution induced large fluorescent enhance-

ment and color change by the spirolactam ring-opening process

of the rhodamine moiety. From the detection of Hg2+ in the

microfluidic channel, the linear responses of compounds105and

106 were observed in the range of 1 nM1 mM Hg2+ concen-

tration with the detection limit of 1 nM for 105and 4.2 nM for

106, respectively. Both chemosensors were applied successfully

to detect previously exposed nanomolar concentrations of Hg2+

in the C. elegans.

Lin et al. reported new fluorescence turn-on Hg2+ probe

107 considering the interaction of Hg2+ with both thiol and

alkyne moieties.138 The probe exhibited large fluorescence

enhancement, high selectivity, low detection limit of 39 nM,

and linear fluorescent response to Hg2+ ranging from 5 108

to 4 106 M. Furthermore, the probe 107 is applicable for

Hg2+ imaging in the living cells. The proposed mechanism is

shown in Fig. 69.

Lin and coworkers constructed a novel reversible fluores-

cence turn-on Hg2+ sensor based on a new receptor composed

of a thiol atom and an alkene moiety for living cell fluorescent

imaging.139 Compound 108 showed a 1000-fold fluorescent

enhancement with Hg2+ in PBS buffer (25 mM, pH 7.0,

containing 2.5% CH3CN) and is highly selective to Hg2+

with a detection limit of 27.5 nM. The S atom and the alkene

moiety of compound 108 took part in the 1 : 1 stoichiometry

binding with Hg2+ and the binding is reversible when excess

EDTA was added under the neutral conditions (Fig. 70).

A rhodamine B-based chemosensor containing NS2 for the

reversible binding receptor of Hg2+ in aqueous media was intro-

duced by Qianet al.140Compound109exhibited quick fluorescent

and colorimetric response that allowed for the real-time detection.

Fig. 66 Structures of compounds 97100 and Hg2+ induced intra-

molecular cyclic guanylation of101.


Fig. 68 Structures of compounds105 and 106.

Fig. 69 Proposed mechanism of107 with Hg2+.

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The 1 : 1 stoichiometry 109/Hg2+ was confirmed by Jobs plot

and the EDTA addition changed the color from pink to colorless

and the fluorescence was turned off (Fig. 71). The binding constant

Kawas calculated to be (1.18 0.13) 106 M1 from the titrationcurve with Hg2+.

Recently, Tang and Nandhakumar et al.reported rhodamine B

hydrazide methyl 5-formyl-1H-pyrrole-2-carboxylate Schiff

base110141 to detect both Cu2+ and Hg2+ using two different

detection modes that are UV-vis spectroscopy for Cu2+ and

selective fluorescent recognition for Hg2+. Despite the copper

ion induced color change with very weak fluorescent emission,

only Hg2+ exhibited fluorescent enhancement by forming the

open-ring form of rhodamine spirolactam in MeOH : H2O

(3 : 1, v/v, HEPES 10 mM, pH 7.4). In addition, compound 110

for sensing Hg2+ is not influenced under neutral pH conditions.

Yuet al.reported compound111 (Fig. 72) as a fluorometric

chemosensor for Hg2+ based on the rhodaminecoumarinconjugate.142 Probe111 showed high sensitivity and selectivity

for Hg2+ sensing with reversible dual-responsive colorimetric

and fluorescent response in 50% water/ethanol buffered at

pH 7.24. The probe 111 can be applied for the recognition of

Hg2+ in both tap and river water samples, and the quantity of

Hg2+

with a linear response ranged from 8.0 108

to 1.0

105 mol L1. The detection limit was 4.0 108 mol L1.

A rhodamine based sensor containing a histidine group was

synthesized for the detection of Hg2+ by the Yoon group.143

As shown in Fig. 72, compound112has two carbonyl oxygens as

well as imidazole nitrogen that can provide a nice storage pocket

for Hg2+. Addition of 100 equiv. Hg2+ caused the fluorescence

increase over 100-fold in 0.02 M, pH 7.4 HEPES : EtOH

(1 : 9, v/v) solution. From the fluorescent titration study with

Hg2+, the association constant of compound 112 was calcu-

lated to be 2.0 103

M1

and thus112 was further applied to

sense the intracellular Hg2+.

Yoonet al.also reported two rhodamine derivatives bearing

mono and bis-boronic acid groups (113and114) as fluorescent

and colorimetric sensors for Hg2+ (Fig. 73). These two

rhodamine derivatives were the first examples of reversible

fluorescent chemosensors, which utilized the boronic acid

group as the binding ligand for metal ions.144 Through the

fluorescent titration with Hg2+ in CH3CNwater (9 : 1, v/v),

the association constants of 114 and 114 with Hg2+ were

calculated to be 3.3 103 M1 and 2.1 104 M1, respectively.

Bis-boronic chemosensor 114 showed 9-fold tighter binding

with Hg2+ than mono-boronic chemosensor 113, due to the

additional boronic acid moiety, which plays an important role

in the recognition of Hg2+

.

The Yoon group introduced rhodamine 6G thiolactone

derivative 115 as a selective and colorimetric sensor for Hg2+

at pH 7.4.145 Offon type fluorescent and colorimetric changes

were observed in the presence of Hg2+ in CH3CNHEPES

buffer (0.01 M, pH 7.4) (1 : 99, v/v). X-Ray structure of

115Hg2+ exhibited the 1 : 2 stoichiometry of 115/Hg2+ and

the sensor 115 could detect Hg2+ in the nanomolar range. In

addition, compound115 could be applied for in vivo imaging of

C. elegans to detect Hg2+. Yoon and Shins group designed a

selenolactone based fluorescent probe 116 for the detection of

inorganic mercury and methylmercury species with unique

fluorescence enhancement and UV-vis spectral change.146 Because

of the extremely high affinity between mercury and selenium,

mercury and methylmercury species induced a deselenation reac-

tion in compound 116 (Fig. 74). In the concentration range of

Hg2+ (030 nM), the fluorescent intensity displayed a linear

response proportionally and the Jobs plot study demonstrated

the binding mode of 1 : 1 stoichiometry between 116 and Hg2+.

This sensing ability was hence successfully applied for the detection

of inorganic mercury/methylmercury species in cells and zebrafish.

Compound 117 (Fig. 75), a tren-spaced rhodamine and

pyrene fluorophore, was reported by the Kim group as a Hg2+

and Cu2+-selective fluorogenic sensor that modulated pyrene

excimer emission.147 The complexation of117with Hg2+ induced

the rhodamine spirolactam ring opening and exhibited dynamic

excimer emission. The different binding mode between Hg2+

and Cu2+ was elucidated from DFT (density functional theory)

Fig. 70 Proposed binding mode of108 with Hg2+.

Fig. 71 Proposed binding mode between109/Hg2+.

Fig. 72 Structures of compounds 110112, and the proposed binding

mode of111 with Hg2+.



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3232 Chem. S

fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions

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