Colorimetric and fluorometric probes for the optical detection of environmental Hg(II) and As(III) ions

Abstract

Human exposure to Hg(II) and As(III) can lead to several physiological problems such as liver damage, kidney damage, lung cancer, skin cancer, motion disorder, brain damage, etc. To monitor and identify these harmful ions, throughout the years enormous effort has been put into the development of sensors. In this review, colorimetric and fluorometric chemical compounds (sensors) for Hg(II) (since 2015) and As(III) detection are described and discussed in detail. For Hg(II), sensors are divided on the basis of the compound's nature, such as heteroatom-based ligand-containing small molecules, rhodamine-based small molecules, reaction-based small molecules, and polymers. On the other hand, most As(III) ion sensors are based on H-bonding interactions.

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1. Introduction

A highly polluted living environment for humankind is a result of modern globalization and industrialization, where water sources are the most affected part while water is the basic and essential ingredient of human life on earth. Heavy metals are one of the most effective pollutants among other sources. Metals with a high atomic number, high density, and which are poisonous at low concentrations are known as heavy metals.^1–3 Heavy metals are harmful due to their tendency to bioaccumulation. Heavy metals can enter the human body through food, drinking water, and air sources. Metals such as arsenic, cadmium, lead, nickel, mercury, chromium, cobalt, zinc, copper and selenium are familiar heavy metals. The accumulation of these metals in our resources is a major concern as many industries discharge their metal wastes into freshwater without any purification.^4,5

Among the mentioned heavy metals, arsenic (As) and mercury (Hg) are the topmost candidates in the context of toxicity. The World Health Organization (WHO) and Environmental Protection Agency (EPA) have defined the permissible limits of concentrations for both mercury and arsenic.⁶

Arsenic poisoning in groundwater is a major concern in several parts of the world, such as Bangladesh, West Bengal, the western USA, Mexico, Chile, and Argentina.⁷ Many electronic component manufacturing industries use trace amounts of arsenic combined with silicon for light-emitting diodes (LEDs) and other devices.⁸ Although in some cases arsenic is used in drugs, chronic exposure can damage the human body. Long-term exposure and usage of arsenic-contaminated water can cause various health risks, such as kidney damage, liver damage, lung cancer, and skin cancer.^9–11 Arsenic can exist in −3 to +5 oxidation states, though the As(III) form is the most toxic to the environment and human health.¹² Due to such toxicity, the WHO set a limit of a safe arsenic (As) concentration in drinking water of 10 ppb.^13,14

Mercury is another heavy metal that is famous for Minamata disease¹⁵ and poisoning in Iraq.¹⁶ Mercury can spread in water, soil, and air from many sources, such as coal plants, mercury lamps, gold production, thermometers, barometers, and caustic soda.¹⁷ Fish is one of the major sources of mercury in humans.¹⁸ Mercury exposure has several harmful effects on health, like kidney failure, motion disorder, and brain damage.^19–21 Methylation of mercury promotes lipid solubility and, as a result, it can easily penetrate biological membranes along with the blood–brain barrier to damage the central nervous system. To avoid the harmful effects of mercury, an upper limit for Hg has been set at 10 nM by the U.S. Environmental Protection Agency (EPA).²²

The extent of toxicity for arsenic and mercury makes it necessary to monitor them in drinking water and different environmental sources with high selectivity and sensitivity. Techniques such as atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectrometry (ICP-MS), atomic fluorescence spectrometry (AFS), high-performance liquid chromatography (HPLC), surface-enhanced Raman scattering, chromatographic techniques, hydride-generation atomic absorption spectroscopy (HG-AAS), and voltammetry studies are used for the detection of arsenic and mercury.^23–33 The above-mentioned techniques are well known for their detection ability in very low concentrations, but they need costly instrumentation and extensive sample preparation. Therefore, the development of simple, cost-effective, and rapid detection methods is very much needed for real-time and ‘on-field’ monitoring of industrial, environmental, and biological contaminated samples.

Among different methods, optical detection through changes in fluorescence or color are most advantageous due to their simple nature and low limit of detection.^34–37 Colorimetric sensors can be useful in the case of the naked eye and rapid detection of analytes without any prior set-up where fluorogenic probes can detect contaminants at the cellular level. Thanks to such advantages, fluorescent and colorimetric sensors have been developed throughout the last few decades for the detection of toxic elements.

To date, three reviews have reported which have provided collective information about various detection systems for environmental Hg²⁺. These reviews discussed optical probes developed up to 2015.^38–40 Furthermore, there have been several reviews for arsenic detection based on the electrochemical method,⁴¹ surface-enhanced Raman spectroscopy (SERS),^42,43 and nano-material systems.^44–46 However, to the best of our knowledge no review based on fluorogenic and chromogenic compounds for As(III) detection has been reported.

In this review, we discuss in detail fluorescent and colorimetric chemical sensors for mercury and arsenic detection. We have classified the sensors depending upon their chemical behavior, such as interaction-based ligand systems, reaction-based irreversible systems, and polymeric materials for a clear and general overview of available sensing materials that have been developed in recent years. Until 2015, there were not such extensive studies on cellular-level tracking of toxic ions. But the new trend of tracking toxic ions at the cellular level has emerged as an excellent technique for a better understanding of their effects on the biological system. Exclusive selectivity and high sensitivity along with cell imaging have become the better outcomes of the sensing field at the present time for mercury and arsenic. Also, many new strategies have been developed in the field of polymer research, where functionalized polymers with sensing moieties have overcome the solubility issue with respect to small molecules and have triggered an improvement in ‘in-field’ applications for the detection of toxic ions. We have tried to give an overall idea of new ways and new developments in mercury and arsenic detection systems based on typical fluorogenic and chromogenic probes.

2. Fluorescent and colorimetric sensors for Hg²⁺ detection

2.1 Heteroatom-based ligand-containing small molecules

Heteroatom-containing ligands associated with a chromogenic or fluorogenic moiety are excellent candidates for the detection of analytes. Ligand-based sensors have been developed over the years with desirable signals and effectiveness for the detection of Hg²⁺ ions in different contaminated sources. In this section we will discuss the formation of Hg–O, Hg–S, Hg–N, etc. bonds due to the interaction of Hg and a ligand to promote some change in color or emission as a detection signal.

In this regard, an N,N-bis(2-(pyridin-2-ylmethoxy)ethyl)aniline receptor containing a boron-dipyrromethene (BODIPY) molecule 1⁴⁷ acts as a fluorescence ‘turn-off’ to ‘turn-on’ sensor for Hg²⁺ (Fig. 1). Here 1 can detect mercury in CH₃CN–water (1 : 1) medium with a limit of detection (LOD) of 1.81 × 10⁻⁷ M. In this case due to the presence of an N,N-bis(2-(pyridin-2-ylmethoxy)ethyl)aniline receptor along with BODIPY, the PET process is in the active mode which results in a fluorescence-off mode in the system. But the addition of Hg²⁺ stopped the photoinduced electron transfer (PET) process by interaction with the N and O atoms of the ligand which triggered the strong emission signal. All these observations made sensor 1 a highly selective and sensitive system for the detection of Hg²⁺ by the naked eye. A pyrene derivative 2⁴⁸ formed a 1 : 2 complex with Hg²⁺ in 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) buffer-CH₃CN (3 : 7, v/v, 10 mM buffer, pH = 7.4) medium (Fig. 1). Due to complexation, 2 showed an unusual red fluorescence and a change in color from yellow to orange along with a 36 nM LOD. The change in color as well as in emission is an advantage for 2.

Fig. 1 The structures of 1 and 2, and their proposed mechanisms of binding with Hg²⁺.

A Schiff-base 3⁴⁹ synthesized from 4-nitro-o-phenylenediamine and 4-formylbenzoic acid showed interesting sensing phenomena for the detection of Hg²⁺ in DMF–water (2 : 3) medium with an LOD of 0.061 μM. Initially, 3 showed green fluorescence, though upon addition of mercury at pH 7 the fluorescence was quenched, but at pH 7.45 fluorescence was turned on again (Fig. 2). The whole phenomenon was described as due to the reduction of intra-molecular charge transfer (ICT) caused by the formation of a strong 5-membered ring between Hg²⁺ and two imine nitrogens at pH 7 and again the introduction of ICT with increasing pH. Due to this interesting behavior of 3 in physiological pH, it has been used in cell imaging studies to extend their application. Sensor 4⁵⁰ also exhibits a ratiometric emission changing phenomenon due to the binding of heteroatoms of 1,8-naphthalimide-sulfamethizole compound with Hg²⁺ in DMSO–water (1 : 99) medium with an LOD 14.7 nM. Binding of Hg²⁺ with –SO₂ and the thiadiazole ring of the sulfamethizole segment of 4 leads to aggregation-induced emission enhancement (AIEE) which is responsible for the selective detection of mercury (Fig. 2).

Fig. 2 The proposed structures and sensing mechanisms of 3 and 4.

Tetraphenylethene derivatives are known for their aggregation-induced emission property. Using this as an advantageous property, sensor 5⁵¹ has been developed by the reaction of 2-(aminooxy)acetic acid and 4-(1,2,2-triphenylvinyl)benzaldehyde. With the addition of mercury to sensor 5 in ethanol–water (3 : 7) medium, the –CH=N and –OH groups coordinate with Hg²⁺ (Fig. 3) and form an aggregate to give a distinct emission with a low LOD of 45.4 nM. BODIPY derivatives are known to have excellent chromophore photochemical and thermal stability, and salen is an excellent ligand system due to its effective coordination behavior with an electron-deficient Lewis-acid (metal center).^52,53 Sensor 6⁵⁴ was designed by the combination of the two above-mentioned advantageous segments for the detection of Hg²⁺. Sensor 6 selectively detected Hg²⁺ among other metal ions by complexation in MeCN–H₂O (v/v, 1 : 1, HEPES 10 mM, pH = 7.4) medium with an LOD of 1.21 μM (Fig. 3). In this particular case, metal-induced intramolecular charge transfer is the reason behind the change in color from colorless to pink to detect Hg²⁺ selectively and sensitively.

Fig. 3 The chemical structures and proposed mechanisms of sensing of 5 and 6.

For biimidazole push–pull dye, sensor 7⁵⁵ coordinates with Hg²⁺ through the thiophene unit (Fig. 4) and stopped the charge transfer process to change the color to colorless from yellow in a CH₃CN–water (1 : 1) mixture with an LOD of 32.8 ppb. With a combination of thiosemicarbazone and 4-(diphenylamino) benzaldehyde, sensor 8⁵⁶ can detect Hg²⁺ in DMSO/Tris–HCl (8 : 2, v/v, pH = 7.0) medium. Hg²⁺ can bind with the sulfur of thiocarbonyl and the nitrogen of the imine group of 8 (Fig. 4) to induce a chelation-enhanced fluorescence quenching (CHEQ) effect. This fluorescence turn-off sensor 8 can detect Hg²⁺ up to a low concentration of 3.11 × 10⁻⁸ M. Sensor 9⁵⁷ is a coumarin–thiol based receptor that detects Hg²⁺ in a CH₃CN–water (3 : 2, v/v, pH = 7) mixture in both colorimetric and fluorometric fashion with an LOD of 5.01 × 10⁻⁸ M. In this case binding of Hg²⁺ with –SH, N of the imine group, and the –C=O group of the coumarin unit of 9 (Fig. 5) induce a color change as well as change in fluorescence. This dual-sensing nature makes 9 a good candidate for mercury detection.

Fig. 4 The chemical structures and proposed binding modes with Hg²⁺ of 7 and 8.

Fig. 5 The chemical structures of 9 and 10 along with their proposed sensing mechanisms.

Phenothiazine-based sensor 10⁵⁸ was designed to detect Hg²⁺ in an ethanol–water (6 : 4, v/v) mixture with an LOD of 17.8 nM. Complexation of Hg²⁺ diaminomalenonitrile moieties of 10 (Fig. 5) inhibits the original ICT process; as a result, quenching of fluorescence and a change in color are observed. With this fluorescence change property, 10 can track cellular Hg²⁺ successfully. Receptor-based sensing models have emerged as a useful tool for the development of Hg²⁺ sensors. A sulfonamide group containing an unnatural peptide receptor with cyanostilbene-based ratiometric fluorogenic probe 11 has been developed.⁵⁹ It binds with Hg²⁺ in such a fashion that it can form an aggregate which is red-emissive (Fig. 6). Sensor 11 is highly selective towards Hg²⁺ in an aqueous buffered solution (10 mM HEPES, pH = 7.4) with an impressive detection limit of 65 nM. This red-emissive nature of 11 is useful for imaging of HeLa cells with Hg²⁺ contamination.

Fig. 6 The chemical structures of 11, 12, and 13 with the proposed mechanism of sensing for 11.

Macrocycles containing sulfur atoms are capable of capturing Hg²⁺. Also, if the BODIPY unit can be functionalized with receptors in the 3 and 5 positions, then the recognition can induce a variation in both emission and absorption. Combining these facts, sensor 12⁶⁰ was developed where N-phenyl-1-aza-4,13-dithia-7,10-dioxacyclopentadecane is attached to the 3 positions of the BODIPY unit (Fig. 6). This BODIPY derivative (12) can detect Hg²⁺ in CH₃CN–water (5 : 95, v/v) medium by a color change as well as turn-on mode of emission change with an LOD of 99 ppm. The design of a fluorescent probe can detect an analyte depending upon different phenomena like PET, FRET, ICT TICT, etc. for the output emission signal. 4-(Methylthio)-2-oxo-2H-pyrano[3,2-c]julolidine-3-carbonitrile derived sensor 13⁶¹ is a twisted intramolecular charge transfer (TICT) active fluorophore, where dipicolyl amine acts as a chelator to bind Hg²⁺ (Fig. 6). The sensing behavior of 13 has been studied in a methanol–HEPES buffer (7 : 3, v/v, pH = 7.2) medium. Sensor 13 detects Hg²⁺ in a ratiometric fashion by changing the emission from red to green with an excellent detection level of 5.7 × 10⁻⁹ M along with tracking of Hg²⁺ in the MCF-7 cell line. Binding with a dipicolylamine unit of 13 with Hg²⁺ restricts the TICT activity which is responsible for the drastic change in emission signal.

Aggregation induced emission (AIE)-based fluorogenic probes are very useful due to their unique fluorescence phenomenon. The tetrathenylethene unit is a well-established moiety for designing AIE-active molecules. Cationic AIE-active sensor 14⁶² consists of tetraphenylethene and quinoline units, and can detect Hg²⁺ by a different method. Initially, 14 showed red fluorescence in aqueous solution (containing 1% DMSO) due to aggregation, but the emission was quenched due to the addition of I⁻ to it. This I⁻-containing sensor 14 system can now act as an Hg²⁺ sensor. Addition of Hg²⁺ to the 14–I⁻ system turns on the red emission again. By this process, 14 can be used as a turn-on fluorescence sensor for Hg²⁺ with a detection limit of 591.9 nM. Another AIE-active sensor 15⁶³ is developed by the conjugation between tetraphenylethene and pyrido[2,3-b]pyrazine units. Sensor 15 has an excellent AIEE phenomenon itself. In the presence of Hg²⁺ in the acetonitrile solution sensor, 15 changed its emission color from red-orange to colorless with a moderate LOD of 7.46 × 10⁻⁶ M. The chemical structure of sensors 14 and 15 are depicted in Fig. 7.

Fig. 7 The chemical structures of sensors 14 and 15.

The 8-hydroxyquinoline based sensor 16 was successfully applied for the recognition of Hg²⁺ (Fig. 8).⁶⁴ In a solution of MeOH–water (1 : 4, v/v), fluorescence quenching was observed for Hg²⁺ with a simultaneous change in emission from blue to colorless. This is a typical example of a turn-off fluorescent sensor where complexation between the sensor and the analyte is responsible for fluorescence quenching.

Fig. 8 The chemical structure of 16 and the proposed sensing mechanism.

Fluorescein as a fluorophore is widely used due to its high molar extinction coefficient, high quantum yield, and strong absorbance along with strong emission signals in the visible range.^65–67 Sensor 17⁶⁸ is a fluorescein dithia-cyclic skeleton which show selective detection ability for Hg²⁺ in an MeOH–Tris–HCl (95 : 5, v/v, pH = 7.2) medium. Upon interaction with Hg²⁺, a drastic color change from yellow to orange was observed along with quenched fluorescence due to the inherent quenching property of mercury (Fig. 9). Another sensor 18,⁶⁹ a Schiff base receptor of fluorescein–phenylalaninol conjugate has been successfully applied for the detection and removal of Hg²⁺. The addition of Hg²⁺ to 18 in aqueous medium changed the color from yellow to pink with quenching of the fluorescence of the system. Binding of Hg²⁺ with the –CH=N and –OH groups is responsible for the quenching of fluorescence as well as color (Fig. 9). Sensor 18 has impressive LODs of 1.65 μM and 0.34 μM, as calculated from absorption and fluorescence studies, respectively. Another fluorescein-derived chemosensor 19 has been reported for the detection of Hg²⁺. Sensor 19⁷⁰ is a fluorescein hydrazide coupled 2-(pyridine-2-ylmethoxy)-naphthalene-1-carbaldehyde moiety which exhibited excellent selectivity and sensitivity towards Hg²⁺ in buffer solution (pH = 7.2, HEPES buffer). Hg²⁺–induced spirolactam ring-opening of the fluorescein moiety is the reason behind the drastic enhancement in fluorescence (Fig. 9). An LOD of 1.24 μM and the ability to track Hg²⁺ at the cellular level make sensor 19 a good candidate in the area of mercury detection.

Fig. 9 The chemical structures of sensors 17, 18, and 19.

Excited-state intramolecular proton transfer (ESIPT)-active molecules are advantageous due to their excellent photostability, large Stokes shift, and unique emission properties. Naphthalene-derived sensor 20⁷¹ is an ESIPT-active probe that has been able to detect Hg²⁺ in CH₃CN–water (9 : 1, v/v, pH = 7.0, HEPES buffer) medium in a fluorescence on to off fashion accompanied by a drastic change in color from colorless to yellow. The interaction between the N and –OH groups of 20 and Hg²⁺ stopped the ESIPT process, resulting in fluorescence quenching (Fig. 10).

Fig. 10 The chemical structures of sensors 20, 21, and 22, and the proposed sensing mechanism of sensor 20.

Terpyridine is a good chromophore that can be introduced to design colorimetric chemical sensors for metal ions. Sensor 21 is a colorimetric fluorescent probe, a combination of a terpyridine unit as a fluorescent moiety and three pyridine rings with ether linkers as receptors (Fig. 10). Sensor 21⁷² is a typical ratiometric fluorescent sensor for Hg²⁺ in aqueous medium by changing the fluorescence from blue to green with an LOD of 0.138 ppm. Initial blue fluorescence is due to weak ICT generated from the terpyridine segment. But after the strong complexation of Hg²⁺ by the receptor, the PET process becomes the driving force for the change in emission color to green. Due to this colorimetric fluorescence change, sensor 21 can be coated on filter paper as paper strips, for the detection of the contaminant in various water sources with the naked eye.

Calix[4]arene-based fluorescent sensing probes are a combination of two parts, i.e.; an ionophore that is responsible for the analyte interaction and a fluorogenic moiety responsible for signal generation. Sensor 22⁷³ is an example of a calix[4]arene-based probe where pyrene is used as a signaling unit (Fig. 10). Sensor 22 can detect Hg²⁺ selectively in CH₃CN–HEPES (6 : 4, v/v, pH = 7.2) medium with an excellent detection limit of 2.94 × 10⁻⁹ M. Complexation between Hg²⁺ and the carbonyl groups of the amide linkages of 22 is the reason behind the fluorescence quenching.

Naked-eye detection of analytes has its uses for cost-effectiveness and simplicity. Sensor 23⁷⁴ is an NBD-based chemosensor (Fig. 11) which detects Hg²⁺ in a methanol–water (1 : 1) mixture by changing the color of the solution from pale yellow to pink with a detection limit of 4.7 × 10⁻⁷ M. The formation of a complex by interaction between 23 and Hg²⁺ triggered the intramolecular charge transfer (ICT) process; as a result, a pink color was observed. Another colorimetric sensor 24,⁷⁵ an azobenzene gelator, acts as a multianalyte detection system (Fig. 11) by changing color. The addition of Hg²⁺ to an acetonitrile solution of 24 resulted in a color change to vermeil from yellow due to complexation. Sensor 24 has an LOD of 9.22 × 10⁻⁹ M towards Hg²⁺ ions.

Fig. 11 The chemical structures of 23, 24 and 25–Hg²⁺.

4-Amino-1,8-napthalimide based fluorogenic probe 25⁷⁶ has been developed to detect Hg²⁺, and it contains iminodiacetic acid and picolinic acid as receptors. Sensor 25 is highly selective and sensitive towards Hg²⁺ in HEPES buffer solution (pH = 7.4) with a moderate LOD of 1.03 × 10⁻⁷ M. A reduced PET process due to the binding of Hg²⁺ with the picolinic acid and iminodiacetic acid receptor of 25 (Fig. 11) is responsible for the turn-on fluorescence signal. Due to the turn-on fluorescence feature, 25 is also able to image cells in the presence of Hg²⁺.

Colorimetric fluorescent sensors have their own advantages due to their dual-mode of signaling, i.e.; by the naked eye and under UV light. Sensor 26,⁷⁷ which is based on one indole ring (Fig. 12), is a typical example of a colorimetric fluorescent probe. Sensor 26 was applied for the detection of Hg²⁺ in HEPES buffer solution (pH = 7.0) by changing the color of the system from light yellow to pink and quenching the emission with a detection limit of 1.08 × 10⁻⁶ M. 1 : 1 binding between Hg²⁺ and 26 resulted in a color change and fluorescence quenching. Sensor 26 can successfully image HeLa cells at pH 7.4 in the presence of Hg²⁺.

Fig. 12 The chemical structures of 26, 27, and 28.

An imidazo[1,2-a]pyridine-based fluorogenic probe 27⁷⁸ was developed to detect Hg²⁺. Sensor 27 (Fig. 12) was able to detect Hg²⁺ in a fluorescence turn-off fashion in EtOH–water (8 : 2, v/v) medium. A 2 : 1 binding stoichiometry is observed between 27 and Hg²⁺ with an excellent detection limit of 1 ppb with imaging of HeLa cells. Unfortunately, 27 suffers from interference by Fe³⁺.

Earlier we discussed one ESIPT sensor. Another ESIPT sensor 28⁷⁹ is a Schiff base type system where an 8-aminoquinoline moiety acts as the binding site for Hg²⁺ ions (Fig. 12). In MeCN–water (3 : 2, v/v, 10 mM HEPES buffer, pH = 7.0) medium, sensor 28 is able to sense Hg²⁺ with a detection limit of 0.11 μM. Upon binding of Hg²⁺ with 28, a strong emission signal is observed due to the disruption of the ESIPT process. Sensor 28 is useful for detecting Hg²⁺ at the cellular level due to the intense emission signal. Again, an ESIPT probe 29⁸⁰ was also developed for the detection of Hg²⁺. Sensor 29 (Fig. 13) differentiates Hg²⁺ from other competitive ions in a fluorescence turn-on fashion in DMF–HEPES solution (1 : 1, v/v, 10 mM, pH = 7.4). The free probe shows a very weak emission as it is in both PET and ESIPT active mode. Upon the addition of mercury, both processes are disrupted to turn on the intense emission. This change in emission from off to on demonstrates the sensing ability of 29 with an LOD of 6.45 × 10⁻⁶ M.

Fig. 13 The chemical structure and proposed sensing mechanism of 29.

Similar to PET, ESIPT, AIEE, etc., TICT is also a well-known phenomenon in the case of fluorescence spectroscopy. Sensor 30⁸¹ is an example of a TICT-active probe, where naphthalene diimide acts as the signaling unit. It can detect Hg²⁺ in acetone medium with a change in emission from colorless to red with a moderate LOD of 3 μM. The change in emission is attributed to the restriction of the TICT process of 30 due to binding with Hg²⁺. Another TICT-active molecule 31⁸² was developed with naphthalene diimide as a signaling unit and bis[2-(3,5-dimethylpyrazole-1-yl)ethyl]amine as an electron donor and ligand for the binding of Hg²⁺. In an acetone–water (1 : 1) medium, sensor 31 can recognize Hg²⁺ (Fig. 14) with a change in fluorescence from colorless to red. The sensing mechanism is quite similar to that of sensor 30. With a 1.3 × 10⁻⁶ M detection limit, sensor 31 is useful for carrying out a biological study for the detection of Hg²⁺ in MCF-7 cells.

Fig. 14 The chemical structures of 30 and 31–Hg²⁺.

Benzothiazole-based sensor 32⁸³ is an example of a colorimetric and fluorescent probe. The addition of Hg²⁺ to 32 (Fig. 15) in CH₃CN–water (1 : 1, v/v, pH = 8.0) medium resulted in a change in color from pink to blue accompanied by a strong emission signal at 425 nm. Thus 32 can be applied to detect Hg²⁺ with a significant range of 2.5 μM by UV-vis and 1.8 ppb by fluorescence emission. A combination of dansyl group and tyrosine developed a turn-on fluorescence sensor 33⁸⁴ which was applied to detect Hg²⁺ in HEPES buffer solution (pH = 7.4). With interaction between two molecules of the sensor 33 (Fig. 15) and one Hg²⁺, the distance between dansyl units is reduced forming a dimer which is responsible for the enhanced fluorescence signal. Such high selectivity and an impressive LOD of 22.65 × 10⁻⁹ M towards Hg²⁺ make sensor 33 an excellent detection system with cell imaging capability.

Fig. 15 The chemical structures of 32 and 33.

We have discussed chemosensors which are based on ligand systems attached to some signaling units. Systems based on different phenomena such as ICT, PET, ESIPT, TICT, and AIEE have been used for the detection of Hg²⁺ by UV-vis and fluorescence spectroscopic techniques. Not all them but many of these sensors can image the cell in the presence of mercury. A summary of the information about the above-mentioned sensors is given in Table 1.

Table 1 A comparison of different chemo-sensors (1–33)

Compound	Medium	LOD	Type of sensing	Biological study
1	CH3CN–water (1 : 1, v/v)	1.81 × 10^−7 M	Turn-on fluorescence	NA
2	CH3CN–HEPES (7 : 3, v/v)	36 × 10^−9 M	Turn-on fluorescence	NA
3	DMF–water (2 : 3, v/v)	0.061 × 10^−6 M	Ratiometric fluorescence	Done
4	DMSO–water (1 : 99, v/v)	14.7 × 10^−9 M	Turn-on fluorescence	NA
5	Ethanol–water (3 : 7, v/v)	45.4 × 10^−9 M	Turn-on fluorescence	NA
6	MeCN–water (1 : 1, v/v)	1.21 × 10^−6 M	Colorimetric	NA
7	MeCN–H2O (1 : 1, v/v)	32.8 ppb	Colorimetric	NA
8	DMSO–Tris–HCl (8 : 2, v/v)	3.11 × 10^−8 M	Turn-off fluorescence	NA
9	MeCN–H2O (3 : 7, v/v)	5.01 × 10^−8 M	Turn-off fluorescence and colorimetric	NA
10	EtOH–water (6 : 4, v/v)	17.8 × 10^−9 M	Turn-off fluorescence	Done
11	Buffered solution containing 1% DMSO	65 × 10^−9 M	Turn-off fluorescence	Done
12	CH3CN–water (5 : 95, v/v)	99 ppm	Colorimetric and turn-on fluorescence	NA
13	MeOH–HEPES (7 : 3, v/v)	5.7 × 10^−9 M	Turn-on ratiometric fluorescence and colorimetric	Done
14	DMSO–water (1 : 99, v/v)	591.9 × 10^−9 M	Turn-on fluorescence	NA
15	CH3CN	7.46 × 10^−6 M	Turn-off fluorescence	Done
16	MeOH–water (1 : 4, v/v)	3.12 × 10^−9 M	Turn-off fluorescence	Done
17	MeOH–Tris–HCl (5 : 95, v/v)	7.38 × 10^−9 M	Turn-off fluorescence and colorimetric	NA
18	Water	0.34 × 10^−6 M	Colorimetric and turn-off fluorescence	NA
19	HEPES buffer	1.24 μM	Turn-on fluorescence	Done
20	CH3CN–water (1 : 9, v/v)	1.24 × 10^−6 M	Turn-off fluorescence	NA
21	Water	0.138 ppm	Turn-on ratiometric fluorescence	NA
22	CH3CN–HEPES (6 : 4, v/v)	2.94 × 10^−9 M	Turn-off fluorescence	NA
23	Methanol–water (1 : 1, v/v)	4.7× 10^−7 M	Colorimetric	NA
24	CH3CN	9.22 × 10^−9 M	Colorimetric
25	HEPES buffer	1.03 × 10^−7 M	Turn-on fluorescence	Done
26	HEPES buffer	1.08 × 10^−6 M	Turn-off fluorescence and colorimetric	Done
27	EtOH–water (2 : 8)	1 ppb	Turn-off fluorescence	Done
28	MeCN–water (3 : 2, v/v)	0.11 × 10^−7 M	Turn-on fluorescence	Done
29	DMF–HEPES solution (1 : 1, v/v)	6.45 × 10^−6 M	Turn-on fluorescence	Done
30	Acetone	3 × 10^−6 M	Turn-on	NA
31	Acetone–water (1 : 1, v/v)	1.3 × 10^−6 M	Turn-on	Done
32	CH3CN–water (1 : 1, v/v)	2.5 × 10^−6 M	Colorimetric and turn-on fluorescence	NA
33	HEPES buffer	22.65 × 10^−9 M	Turn-on fluorescence	Done

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2.2 Rhodamine-based ligand systems for the detection of Hg²⁺

We have discussed heteroatom-based ligand systems (1–33) which consist of different fluorogenic and chromogenic moieties apart from rhodamine, for the detection of Hg²⁺. Among several dyes available as a fluorophore, rhodamine dyes are well known for their unique features, such as high absorption coefficient, long excitation wavelength, strong absorption, emission signal in the visible range and high quantum yield. Due to such extensive features, rhodamine is being used as the basic unit for the development of fluorescent and colorimetric probed to detect metal ions.^85–89 In this section we are going to discuss reported Hg²⁺ sensors based on rhodamine derivatives with ligand systems.

For the binding of Hg²⁺, a phthalaldehydic has been combined with rhodamine 6G to synthesize sensor 34.⁹⁰ Spirolactam ring-closed derivative 34 formed a colorless solution in a MeOH–water (1 : 1, v/v) mixture with no emission. Upon the addition of Hg²⁺, the solution instantly changed color to pink with a strong yellow fluorescence. Strong 1 : 1 binding between 34 and Hg²⁺ resulted in the spirolactam ring-opening of the rhodamine derivative (Fig. 16), credited with the color and fluorescence change with an excellent lower detection limit of 5 pM, Due to this turn-on fluorescence behavior of 34, it has been used for the detection of Hg²⁺ in HeLa and macrophage cells.

Fig. 16 The chemical structures of sensors 34 and 35 along with their proposed sensing mechanism.

Sensor 35⁹¹ is a rhodamine–tryptamine-coupled fluorogenic and chromogenic sensor. Tryptamine is analogous to tryptophan and acts as a neurotransmitter. The carbonyl oxygen of rhodamine is replaced by sulfur as Hg²⁺ has a high affinity towards thio groups. Initially, 35 has no color or fluorescence in MeOH–water (7 : 3) medium, but the sudden appearance of a pink color along with orange-red emission has been observed upon the addition of Hg²⁺. The high thiophilic affinity of Hg²⁺ results in spirolactam ring-opening (Fig. 16) and a simultaneous change in color and fluorescence. A strong 1 : 1 binding stoichiometry between Hg²⁺ and 35 and naked-eye visualization of a change in color as well as fluorescence established the excellent sensing capacity of the sensor with an extremely low detection limit of 2.1 nM.

Another rhodamine-derived sensor 36 has been applied for the detection of Hg²⁺. Slight modification has been undertaken to make the sensor different from the rhodamine B unit, where one side of the xanthene moiety has been substituted by piperazine and further functionalized with naphthyl chloride to develop sensor 36.⁹² A closed spirolactam ring has been formed by the introduction of hydrazine, which acts as the binding segment for Hg²⁺. In an MeCN–water (7 : 3, v/v) mixture, sensor 36 showed no color or emission. But upon the introduction of Hg²⁺ to the solution, the sudden appearance of a pink color and yellow fluorescence has been observed. Initial binding of Hg²⁺ (Fig. 17) with 36 induces spirolactam ring-opening followed by hydrolysis for the formation of rhodamine acid, leading to the change in color as well as fluorescence. Sensor 36 has a moderate LOD of 0.38 μM and can be applied to stain living cells. Similarly, a combination of thioxo-rhodamine B hydrazine with [2,2′-bithiophene]-5-carboxaldehyde and [2,2′-bithiophene]-5,5′-dicarboxaldehyde leads to the development of sensors 37a and 37b, respectively.⁹³ These two sensors have different modes of action, although Hg²⁺–induced spirolactam ring-opening is common to both. The sensing behavior of both sensors was carried out in EtOH–HEPES (1 : 1) medium. Initially, the solutions of both 37a and 37b have no color or emission. Upon the addition of Hg²⁺, both showed a pink color with reddish-orange emission. Complexation of Hg²⁺ with 37a triggers spirolactam ring-opening to activate the color and fluorescence of the rhodamine unit upon the excitation wavelength of the bithiophene moiety which suggests a FRET mechanism. In the case of 37b, the sensing mode is different from that of 37a, a traditional Hg²⁺–induced spirolactam ring-opening upon binding in the cavity formed by thiophene and rhodamine unit is credited with the color change and emission change. The LOD values for 37a and 37b are 3.1 × 10⁻⁹ M and 2.92 × 10⁻⁹ M, respectively. These naked-eye fluorescent sensors are capable of detecting Hg²⁺ in living cells. The proposed sensing mechanisms of 37a and 37b are mentioned in Fig. 18.

Fig. 17 The chemical structure and proposed sensing mechanism of sensor 36.

Fig. 18 The chemical structures of 37a and 37b and their proposed sensing mechanisms.

Another sensor 38⁹⁴ was designed by the attachment of hexaphenylbenzene and rhodamine units (Fig. 19). Initially, sensor 38 showed AIEE in a water–MeCN (1 : 1) mixture and formed fluorescent aggregates. The aggregates showed blue fluorescence due to the stacking of hexaphenylbenzene units. After the addition of Hg²⁺ to the solution, the fluorescence signal of 475 nm (blue emission) decreased and a new signal at 582 nm (orange-red emission) appeared with an intense pink color. The opening of the spirolactam ring by Hg²⁺ triggers the FRET process from hexaphenylbenzene (donor) to the rhodamine unit (acceptor). Thus, sensor 38 has evolved as an excellent tool for the detection of Hg²⁺ both in water sources and at a cellular level with a detection limit of 100 nM.

Fig. 19 The chemical structure and proposed sensing mechanism of 38.

Slightly modified rhodamine B derivative 39⁹⁵ was developed by the reaction between thiocarbonyl-functionalized rhodamine B and different substituted cinnamyl aldehydes. In an EtOH–water (1 : 1, v/v, PBS, Ph 7.4) mixture, all the derivatives of 39 have been applied for the detection of Hg²⁺ with the same mode of action. Spirolactam ring-opening and binding of Hg²⁺ through C=S and C=N segments resulted in a color change and fluorescence change (Fig. 20). All the derivatives are capable of tracking Hg²⁺ in living cells as well as in animal systems. The sensor consisting of H-functionalized cinnamyl aldehyde, has the maximum efficiency towards Hg²⁺ detection.

Fig. 20 The chemical structures of 39, 40, and 41, and the proposed sensing mechanisms of 39 and 40.

Another sensor 40,⁹⁶ a combination of diphenyl selenium and rhodamine B hydrazide was applied for the selective and sensitive detection of Hg²⁺ in MeOH–water (9 : 1, v/v) medium. Traditional Hg²⁺-induced spirolactam ring-opening followed by complexation with 40 resulted in a color change and fluorescence change (Fig. 20). With an impressive LOD of 12 nM, sensor 40 is capable of detecting Hg²⁺ in living cells and zebrafish. A similar kind of rhodamine 6G derivative 41⁹⁷ has been developed for the selective and sensitive detection of Hg²⁺ in DMSO–water (1 : 1) medium with an acceptable LOD of 2.07 × 10⁻⁸ M. An initial weak emission band at 575 nm of 41 is due to a PET process but after the addition of Hg²⁺, a drastic enhancement in fluorescence intensity at 575 nm has been observed as a result of a chelation-enhanced fluorescence (CHEF) process (Fig. 20). The visual detection ability of 41 enabled the development of paper strips for the detection of Hg²⁺.

From the condensation of thiobisethylamine with rhodamine B was developed a simply synthesized sensor 42.⁹⁸ A solution of 42 in MeCN–HEPES (1 : 99, v/v) showed no color and no fluorescence, but the addition of Hg²⁺ resulted in a sudden color change and fluorescence change. Complexation between Hg²⁺ and 42 through an oxygen atom of the amide carbonyl group, S, and N atoms of the thiobisethylamine unit (Fig. 21) simultaneously opened the spirolactam ring which triggered the color and fluorescence change. With a moderate LOD of 0.14 μM, 42 has the capability of imaging cells in the presence of Hg²⁺.

Fig. 21 The chemical structures of 42 and 43. The proposed sensing mechanism of 42.

Another sensor 43,⁹⁹ a combination of 2-hydroxy acetophenone and rhodamine hydrazine, was applied for the selective and sensitive detection of Hg²⁺ in an EtOH–water (2 : 1, v/v) buffer (10 mM, HEPES, pH = 7.2) mixture. The solution of 43 turned pink upon the addition of Cu²⁺ and Hg²⁺, though enhanced reddish-orange fluorescence has been observed only in the case of Hg²⁺. Strong 1 : 1 binding (Fig. 21) between the ion and 43 is attributed to spirolactam ring-opening and subsequent color and fluorescence change with a detection limit of 150 nM.

A combination of a dialdehyde derivative of bisphenol A and N-(rhodamine-B) lactam-ethylenediamine developed a dual-channel probe 44,¹⁰⁰ which has been applied for the selective detection of Hg²⁺ by the FRET phenomenon. In an MeCN–water (8 : 2, v/v, HEPES, Ph = 7.0) mixture, 44 showed an excellent pink color along with orange fluorescence upon the addition of Hg²⁺. Spirolactam ring-opening of the rhodamine unit by Hg²⁺ forms a new conjugate system and activates the FRET process from the bisphenol (donor) unit to the rhodamine (acceptor) unit to give the orange emission as an output signal (Fig. 22). This emissive property of 44 can be used in the detection of Hg²⁺ in living cells.

Fig. 22 The chemical structures of 44 and 45 and their proposed sensing mechanisms.

Ratiometric sensor 45,¹⁰¹ a combination of a BODIPY unit and a rhodamine unit, was developed very cleverly. A combination of these two units has been used as a FRET pair, where the BODIPY unit can act as a donor and the rhodamine unit as an acceptor. These two units have been attached by a thiophene unit, which can act as a binding unit of Hg²⁺. An ethanolic solution of 45 showed only a green fluorescence due to the BODIPY unit. But upon the addition of Hg²⁺, reddish-orange emission observed upon excitation at 480 nm (BODIPY moiety) due to spirolactam ring-opening followed by FRET activation (Fig. 22). This FRET pair has an excellent LOD value of 1.56 ppb.

Sensor 46¹⁰² was also developed by the sequential reactions between rhodamine B, triethylenetetramine, and phenyl isothiocyanate (Fig. 23). Thiourea segments of 46 are responsible for the interaction with Hg²⁺. In MeCN–HEPES (9 : 1, v/v) medium, 46 and Hg²⁺ formed a stable 1 : 3 complex with a strong orange emission accompanied by a pink color. Similarly, another rhodamine-based sensor 47 (Fig. 23) has been developed with the combination of rhodamine B and -thiophene acetyl chloride.¹⁰³ This thiophene-coupled rhodamine derivative 47 was applied for the detection of Hg²⁺ in an EtOH–water (2 : 1, v/v) mixture. Spirolactam ring-opening induced by Hg²⁺, followed by the complexation with 47 resulted in a pink coloration and reddish emission. An LOD of 0.11 μM and the ability to image living cells and zebrafish helped 47 to become a potential tool for the detection of Hg²⁺.

Fig. 23 The chemical structures of 46 and 47.

In this section, we have discussed reported sensors of Hg²⁺ based on heteroatom-containing ligands and rhodamine units as the signaling moiety. The rhodamine unit has been successfully used as the signaling unit as it has both colorimetric and fluorometric properties in spirolactam ring-closed form. Rhodamine-based sensors can show turn-off to turn-on fluorescence activity upon interaction with metal ions. Hg²⁺ can induce the opening of the spirolactam ring in rhodamine derivatives and switch on the color as well an emission. Due to this unique feature, modified rhodamine molecules are one of the most commonly used tools for the detection of Hg²⁺ ions. All the comparative data are described in tabular form in Table 2.

Table 2 A comparison of different rhodamine-based chemosensors (34–47) for Hg²⁺

Compound	Medium	LOD	Type of sensing	Biological study
34	MeOH–water (1 : 1, v/v)	5 × 10^−12 M	Colorimetric and turn-on fluorescence	Done
35	MeOH–water (7 : 3, v/v)	2.1 × 10^−9 M	Colorimetric and turn-on fluorescence	NA
36	MeCN–water (7 : 3, v/v)	0.36 × 10^−6 M	Colorimetric and turn-on fluorescence	Done
37a	EtOH–HEPES (1 : 1, v/v)	3.1 × 10^−9 M	Colorimetric and turn-on fluorescence	Done
37b	EtOH–HEPES (1 : 1, v/v)	2.92 × 10^−9 M	Colorimetric and turn-on fluorescence	Done
38	MeCN–water (1 : 1, v/v)	100 × 10^−9 M	Colorimetric and turn-on fluorescence	NA
39	EtOH–water (1 : 1, v/v, PBS, pH = 7.4)	8.26 × 10^−9 M, 15.52 × 10^−9 M, 23.26 × 10^−9 M	Colorimetric and turn-on fluorescence	Done
40	MeOH–water (9 : 1, v/v)	12 × 10^−9 M	Colorimetric and turn-on fluorescence	Done
41	DMSO–water (1 : 1, v/v)	2.07 × 10^−8 M	Colorimetric and turn-on fluorescence	NA
42	MeCN–HEPES (1 : 99, v/v)	0.14 × 10^−6 M	Colorimetric and turn-on fluorescence	Done
43	EtOH–water (2 : 1, v/v)	150 × 10^−9 M	Colorimetric and turn-on fluorescence	NA
44	MeCN–water (8 : 2, v/v, HEPES, Ph = 7.0)	2.16 × 10^−6 M	Colorimetric and turn-on fluorescence	Done
45	EtOH	7.8 × 10^−9 M	Colorimetric and turn-on fluorescence	NA
46	MeCN–HEPES (9 : 1, v/v)	3.04 × 10^−7 M	Colorimetric and turn-on fluorescence	NA
47	EtOH–water (2 : 1, v/v)	0.11 × 10^−6 M	Colorimetric and turn-on fluorescence	Done

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2.3 Reaction-based irreversible sensors for Hg²⁺

The above-mentioned sensor systems can detect Hg²⁺ complexation with the ligands and they can also be reversible. These interaction-based systems are one kind of developed tool that can be used for the detection of analytes, but there is always a chance of interference by other metal ions with the same type of chemical properties. But reaction-based detection systems are preferable due to their high selectivity over other competitive metal ions. Thioacetal deprotection, 1,3,4-oxadiazole formation, ester hydrolysis, hydrolysis of an imine bond, and alkyne or vinyl ether oxymercuration are well-known reactions which are preferably carried out by Hg²⁺. These reactions have been used to design and develop different sensing systems for Hg²⁺ over the years. In this section, we are going to discuss reaction-based sensing systems that have evolved over the last few years.

2.3.1 Thioacetal deprotection. Thioacetal deprotection is one of the most important reactions which is done selectively by the Hg²⁺ ion. Using this to their advantage, many sensing systems have been developed to sense mercury with high selectivity. With this virtue, a simple benzothiazole-based fluorescent probe 48¹⁰⁴ has been designed for the detection of Hg²⁺. In this compound, one of the aldehyde groups has been protected by 1,3-propanedithiol to form thioacetal which is the reaction site for Hg²⁺. Initial green fluorescence of 48 in PBS buffer (pH 7.4, containing 2% DMSO) solution is observed due to the ESIPT process between the benzothiazole moiety and adjacent –OH group as well as due to the presence of the electron-donating group thioacetal. After the addition of Hg²⁺, green fluorescence shifted to blue fluorescence in a ratiometric manner. Hg²⁺ deprotects the thioacetal to form an electron-withdrawing aldehyde group which is the reason for the observed blue shift in emission (Fig. 24). Due to this deprotection behavior of Hg²⁺ towards thioacetal groups, 48 becomes a highly selective and ratiometric fluorescent tool for sensing purposes with an LOD of 7.6 × 10⁻⁹ M. Sensor 48 also has the capability of sensing mercury ions in biological systems.

Fig. 24 The chemical structures and proposed sensing mechanisms of 48 and 49.

Similarly, an oligothiophene-based thioacetal system 49¹⁰⁵ has been developed as an excellent colorimetric and fluorometric probe for the detection of Hg²⁺ in EtOH–water (1 : 1) medium. Sensor 49 has a strong blue fluorescence due to the stopped ICT process as well as having no color. But upon addition of Hg²⁺, the color of 49 changed from colorless to yellow accompanied by yellow fluorescence. The formation of an aldehyde group from thioacetal is promoted by Hg²⁺ (Fig. 24) which activates the ICT process, which is responsible for the color change as well as the fluorescence change. Sensor 49 can detect Hg²⁺ in water, soil, and seafood with a detection limit of 1.03 × 10⁻⁸ M.

Benzothiazole-based “ESIPT + AIE”-active probe 50¹⁰⁶ was designed for the selective detection of Hg²⁺ in THF–water (1 : 1, v/v, PBS, Ph = 8.5) medium. The aldehyde group was protected by 3-marceptopropionic acid to make it an Hg²⁺-reactive compound. Hg²⁺-triggered hydrolysis of 50 (Fig. 25) resulted in the formation of an “ESIPT-AIE”-active molecule which shows a strong yellow fluorescence. This distinct change in emission can be effectively applied for biological study. Sensor 50 has an impressive detection limit of 1.59 × 10⁻⁸ M. Similarly a colorimetric and fluorescent probe 51,¹⁰⁷ based on a benzo[1,2-b:4,5-b′]dithiophene (BDT) unit has been developed for the detection of Hg²⁺, where a thioacetal group is used as the reaction site. Sensor 51 has been applied for the detection of Hg²⁺ in a THF–water (1 : 1) mixture with a change of color to yellow from colorless and yellow emission from blue. Thioacetal deprotection to aldehyde formation (Fig. 25) of sensor 51 promoted by Hg²⁺ is the reason behind the color change as well as the emission change. Due to its reaction-based sensing mechanism, sensor 51 emerged as a highly selective Hg²⁺ sensor with a moderate LOD of 3.1 × 10⁻⁷ M.

Fig. 25 The chemical structures and proposed sensing mechanisms of 50 and 51.

A 1,3-dithiane group has been incorporated into a dicyanomethylene-4H-pyran fluorophore for the design of a dual colorimetric and NIR fluorescent probe 52.¹⁰⁸ Sensor 52 has been applied for the detection of Hg²⁺ in a PBS–DMSO buffer (20 mM, pH 7.4, 5 : 5, v/v) mixture. Hg²⁺–Induced deprotection of the thioacetal segment changes the color to pink from purple with an emission signal around the NIR area (Fig. 26). 52 can successfully detect selectively only Hg²⁺ among other metal ions due to the thiophilic nature of mercury. This dual-channel detection system has an LOD value of 6.8 × 10⁻⁸ M. Due to its prominent and visual color change as well as emission signal around the NIR zone, it can be applied in biological systems and the environment for the detection of Hg²⁺.

Fig. 26 The chemical structures and proposed sensing mechanisms of sensors 52 and 53.

Another sensor 53¹⁰⁹ consists of benzothiazole as a core unit. The presence of the thioacetal group stops the ICT process and activates the ESIPT between –OH and the benzothiazole unit; as a result, blue fluorescence has been observed in a pH 7.4, 10 mM HEPES buffer–ethanol (1 : 1, v/v) mixture. Upon addition of Hg²⁺ to the mixture of 53, intense greenish-yellow emission was observed by decreasing the blue emission. ICT along with ESIPT has been activated due to the appearance of the –CHO group by Hg²⁺-triggered deprotection of thioacetal (Fig. 26). Due to the ratiometric nature of the detection and low LOD of 5.8 nM, sensor 53 can act as a good tool for the detection of Hg²⁺, though it lacks biological application.

A simple pyrene derivative 54a^110a containing a bisethylsulfane moiety has been applied to sense Hg²⁺ in semi-aqueous medium and biological systems. Sensor 54 can detect Hg²⁺ selectively due to the presence of the bisethylsulfane segment. Hg²⁺ promotes the removal of bisethylsulfane to produce 1-pyrenecarboxaldehyde (Fig. 27) in MeCN–water (1 : 1, v/v) medium with the appearance of blue emission. Sensor 54a has a detection limit of 57 nM and can successfully detect Hg²⁺ in living cells and zebrafish.

Fig. 27 The chemical structures and proposed sensing mechanisms of 54a, 54b and 54c.

Another dithiolane-based probe 54b^110b has been successfully applied to identify Hg(II) in ethanol/water (2 : 8, v/v; pH = 7.40) medium. Due to the protected form of the –CHO group in the naphthalene moiety, the fluorescence intensity is weak initially. After addition of Hg(II), a colour change to light green from light yellow and strong emission were observed. This change in colour and emission is expected due to the transformation of dithiolane to a formyl group (Fig. 27). Sensor 54b turned out to be an excellent sensor for Hg(II) with a detection limit of 4.0 × 10⁻⁸ M and ability for cell imaging.

Probe 54c^110c has been reported as an excellent small molecular probe for Hg(II) detection. In a 99% PBS buffer solution of 54c, with the addition of Hg(II), the solution turned green-emissive from non-emissive. Here also the dithiolane segment has been used as selective reaction site for Hg(II). By virtue of this the formation of a –CHO group triggered by Hg(II) leads to the observed green emission (Fig. 27). As a reaction-based sensor, 54c is highly selective towards Hg(II) and suffered zero interference by other analytes. It has been successfully applied in a paper-strip model and for analysis of Hg(II) contamination in real samples. The limit of detection for 54c is calculated as 19.3 nM.

Another sensor 55 consists of a π-extended anthracene moiety bearing thioacetal segments within it.¹¹¹ In a solution of a THF–PBS buffer (1 : 1, v/v, pH = 7.4) mixture, sensor 55 showed weak blue fluorescence. After the addition of mercury, successful deprotection of thioacetal formed the aldehyde. Aldehyde formation from thioacetal (Fig. 28) triggered the intense green emission which contributed to the effectiveness of the chemodosimetric nature of 55 with an LOD of 59 nM. Due to this ratiometric change in emission, 55 was utilized for the detection of Hg²⁺ in living cells.

Fig. 28 The chemical structures and proposed sensing mechanisms of 55 and 56.

Coumarin-based fluorescent probe 56¹¹² was developed by introducing a 2-aminophenyl group to the Hg²⁺/CH₃Hg⁺-reactive thioacetal group. In a PBS buffer solution of 56, the introduction of Hg²⁺ ions resulted in aldehyde formation from thioacetal followed by condensation with an adjacent –NH₂ group to form a heterocyclic aromatic compound with large conjugation (Fig. 28). Due to the formation of the heterocyclic aromatic compound with a coumarin ring, bright green emission was observed with the shifting of the emission spectrum. Sensor 56 is able to detect both Hg²⁺ and CH₃Hg⁺ with the same mode of sensing mechanism and green emission as an output signal. The LOD values are 27 nM and 5.7 μm for Hg²⁺ and CH₃Hg⁺, respectively.

In this section, we have discussed thioacetal-based probes for the irreversible detection of Hg²⁺ in the environment and biological systems.

2.3.2 Vinyl ether oxymercuration. The hydrolysis of vinyl ether by Hg²⁺ is one design that can make the sensor highly selective. This so-called oxymercuration reaction can overcome the selectivity issue compared to probes based on heteroatom-containing ligands. Also, in most cases this vinyl ether hydrolysis leads to turn-on fluorescence which is much preferable for tracing Hg²⁺ as well as CH₃Hg⁺ in both the environment and biological systems. In this section, we are going to discuss some reported chemodosimeters for mercury detection based on the hydrolysis of the vinyl ether group.

Fluorescent probe 57¹¹³ consisting of coumarin as a fluorophore moiety and vinyl ether as the reactive site was developed for the detection of Hg²⁺. Sensor 57 in HEPES buffer solution showed no emission but upon addition of Hg²⁺ the sudden appearance of blue emission was observed. The irreversible hydrolysis reaction of the vinyl ether group promoted by Hg²⁺ (Fig. 29) is the reason behind the turn-on fluorescence response of 57 with a detection limit of 0.12 μM. Similarly, another sensor 58¹¹⁴ comprises an O–vinyl protected hydroxyl benzaldehyde coupled with rhodamine hydrazone. Initially 58 in CH₃CN–PBS buffer (3/7, v/v, 10.0 mM, pH = 7.40) solution exhibited green fluorescence due to the ICT process. After the addition of Hg²⁺, the green fluorescence of 58 decreased due to the deprotection of the vinyl ether group which inhibited the ICT process (Fig. 29). With the turn-off emission of 58 in the presence of Hg²⁺, it has a detection limit of 244 ppb.

Fig. 29 The chemical structures of 57 and 58 along with their proposed sensing mechanisms.

Sensor 59,¹¹⁵ based on a vinyl ether derivative of hemicyanine, has been developed for the detection of Hg²⁺. Deprotection of the –OH group of hemicyanine by a vinyl group blocks the ICT process. Hydrolysis of vinyl ether promoted by Hg²⁺ in 59 (Fig. 30) activates the ICT process in the HEPES buffer solution, which is responsible for the appearance of an orange color as well as reddish-yellow fluorescence. This drastic change in color and fluorescence of 59 appears to be advantageous in the field of Hg²⁺ detection with biological applications.

Fig. 30 The chemical structure and proposed sensing mechanism of 59.

An NIR-fluorescent probe 60¹¹⁶ was developed, where 9-(2-carboxyphenyl)-6-(diethylamino)-1,2,3,4-tetrahydroxanthylium was used as a fluorophore and vinyl ether acted as the reactive site for Hg²⁺. Sensor 60 in ethanol–H₂O (2 : 8, v/v 50 mM HEPES buffer solution, pH = 7.4) solution initially showed a weak red emission at 660 nm but upon the introduction of Hg²⁺, a drastic enhancement in 660 nm peak with strong red emission was observed. This change in emission was due to the removal of the vinyl ether group and the formation of an –OH group which increases the “push–pull” property to activate the ICT process (Fig. 31). Due to the turn-off to turn-on nature of 60 in the presence of Hg²⁺, it is very useful in the environment and biological systems. This NIR probe has an LOD value of 3.2 nM.

Fig. 31 The chemical structures and proposed sensing mechanisms of 60 and 61.

Another sensor 61¹¹⁷ was developed for the selective and sensitive detection of Hg²⁺ with the help of a vinyl ether group as the reaction site. Initially, blue fluorescence of 61 was observed in 10 mM PBS buffer (1% CH₃CN) solution which was due to the stopped ESIPT process. But after the addition of Hg²⁺ to the PBS buffer solution, an equivolume of DCM was added and fluorescence was recorded, a drastic red shift of the emission spectrum was observed with a cyan emission. Deprotection of the vinyl ether group promoted by Hg²⁺ and formation of –OH group (Fig. 31) activate the ESIPT process which was the reason for cyan fluorescence. Sensor 61 is an excellent chemodosimeter due to its ratiometric nature and an impressive LOD of 7.8 × 10⁻⁹ M. It can also be applied in biological systems to detect Hg²⁺ with good efficiency.

2.3.3 Other reaction-based sensors. In this section, we are going to discuss other reaction-based approaches for the detection of Hg²⁺, such as hydrolysis of esters or imine bonds, and 1,3,4-oxadiazole formation. Sensor 62¹¹⁸ consists of a 2-mercapto-benzyl ester group as the reaction site forester hydrolysis. 4-[2-(4-Hydroxy-phenyl)-vinyl]-1-methyl-pyridinium[e]iodide was used as the signaling unit due to its high water solubility. In a 100% PBS buffer solution, sensor 62 shows no emission due to the ester moiety which inhibits the intramolecular charge transfer process. But upon addition of Hg²⁺ ion, it coordinates with the –SH and C=O groups of the 2-mercapto-benzyl segment to facilitate the hydrolysis reaction to form an –OH group of the fluorophore (Fig. 32). This hydrolysis reaction triggers activation of the ICT process to show a green-yellow emission signal. Sensor 62 acted as a turn-on chemodosimeter for the detection of Hg²⁺ with a detection limit of 6.5 nM. Another sensor 63,¹¹⁹ a Schiff base type of compound containing benzimidazole and coumarin units as fluorophores, was developed for the selective detection of Hg²⁺ in HEPES buffer/DMSO (v/v = 9 : 1, pH = 7.2) medium. Initial weak blue emission turned intense blue upon the addition of Hg²⁺ into the solution of 63. This enhanced emission signal is expected to be due to the cleavage of the imine bond by Hg²⁺ and the formation of the coumarin part (Fig. 32). With a high sensitivity of 70 nM, 63 can be applied for the detection of Hg²⁺ in biological systems.

Fig. 32 The chemical structures and proposed sensing mechanisms of 62 and 63.

Similarly, sensor 64¹²⁰ was developed using a coumarin derivative and a 5-aminoisophthalic acid methyl ester unit. Due to the formation of the Schiff base between coumarin dye and the amino isophthalic acid methyl ester derivative in CH₃CN–H₂O (8/2, v/v, 0.1 M KClO₄ buffer, pH = 7.34) medium, no emission was observed. Upon the addition of Hg²⁺, a highly intense peak at 490 was observed. The resulting emission signal corresponded to the coumarin aldehyde unit which was a result of imine bond cleavage promoted by Hg²⁺ to suppress the PET process (Fig. 33). Sensor 64 was successfully applied to detect mercury at the nanomolar level with biological applications.

Fig. 33 The chemical structure and proposed sensing mechanism of 64.

An imidazo[1,2-a]pyridine-rhodamine ratiometric fluorescent probe 65¹²¹ was developed for the detection of Hg²⁺ in PBS/EtOH (9 : 1, v/v) medium. Upon addition of Hg²⁺ to the solution of 65, it turned pink in color with a reddish emission. Hg²⁺ promoted spirolactam ring-opening followed by the formation of 1,3,4-oxadiazole by thiosemicarbazide (Fig. 34). Due to this new structure formation and extended conjugation, the FRET process was generated to give a unique color and emission. Sensor 65 has an LOD of 9.1 nM and the capability of tracking mercury at the cellular level with excellent efficiency.

Fig. 34 The chemical structures and sensing mechanisms of 65 and 66.

Another sensor 66¹²² was developed as a pyrido[1,2-a]benzimidazole-rhodamine based FRET system. In this system, benzimidazole was used as the energy donor and a piperazine-functionalized rhodamine unit was used as the acceptor of energy. In a solution of EtOH–water (2 : 8, v/v), 66 shows blue emission with no color. After the addition of Hg²⁺, the sudden appearance of a pink color with red emission was observed upon excitation at 380 nm which corresponds to the benzimidazole moiety. The mechanism is similar to that of sensor 65, where the formation of 1,3,4-oxadiazole and spirolactam ring-opening (Fig. 34) is the reason behind the color change and emission change. Sensor 66 with a good LOD of 18.8 nM, can be applied for detecting Hg²⁺ in biological systems.

Sensor 67¹²³ was developed with the combination of rhodamine B, o-phenylenediamine, and phenyl isothiocyanate. Initially a solution of 67 in MeCN–HEPES (1 : 9, v/v, pH = 7.2) medium showed no color and no emission. The addition of Hg²⁺ to the solution resulted in a pink color and reddish emission. Hg²⁺ promoted spirolactam ring-opening followed by the formation of a benzimidazole-appended rhodamine intermediate (Fig. 35) to generate the color as well as the emission output. The dual-mode of detection of 67 in a chemodosimetric manner made it much more useful with an LOD of 1.6 nM and biological applicability.

Fig. 35 The chemical structures and proposed sensing mechanisms of 67, 68a and 68b.

Another sensor 68 was designed with a perimidine moiety for the detection of Hg²⁺ ions. In a MeCN–water (3 : 7, v/v) mixture, 68a^124a showed no emission. A strong blue emission was observed for 68a upon the addition of Hg²⁺. The blue emission signal is attributed to the Hg²⁺-mediated formation of a double bond in the junction of the coumarin and naphthalin moiety (Fig. 35). Sensor 68a suffered from a low LOD of 1.08 μM although it can be applied in biological systems to detect Hg²⁺.

Another azo-based sensor 68b^124b has been introduced for the successful colorimetric detection of Hg(II) in a DMSO–water (1 : 99, v/v) system. Here the Hg(II)-triggered desulfurization and subsequent rearrangement leads to the change in colour for 68b (Fig. 35). This system is an excellent molecule to detect Hg(II) with an LOD of 8.1 nM and can be used as a solid chip to visualize the colour change.

A combination of the dye pyronin and the chelating agent meso-2,3-dimercaptosuccinic acid developed sensor 69¹²⁵ for the detection and removal of Hg²⁺. This one of the rare systems which can detect and sense Hg²⁺ ions. In PBS buffer solution, 69 remained in turn-off fluorescence mode and was colorless to the naked eye. Upon introduction of Hg²⁺, a solution of 69 turned pink in color and emitted reddish fluorescence. Strong binding of Hg²⁺ with the ligand and subsequent removal of the chelated complex generated free pyronin dye to which was attributed the appearance of the pink color and reddish emission (Fig. 36). With the excellent dual-sensing signal and high LOD of 300 pM, sensor 69 was successfully applied at the cellular level and in a zebrafish model for tracking Hg²⁺.

Fig. 36 The chemical structures and proposed sensing mechanisms of 69 and 70.

The thiocarbonate-appended fluorescein-based chemodosimeter 70¹²⁶ was developed for the turn-on fluorescent detection of Hg²⁺ in a HEPES buffer solution (20 mM, pH 7.4, 1% EtOH). Initially, with no color and emission, 70 showed green emission upon the addition of Hg²⁺. Hg²⁺ promotes the hydrolysis of the thiocarbonate segment and forms free fluorescein acid which results in a greenish emission (Fig. 36). Sensor 70 has a detection limit of 40 nM.

Another thiocarbonate-based sensor 71¹²⁷ was developed, where 2-(2′-hydroxyphenyl)benzothiazole was used as the fluorophore unit. Benzothiazole segments are well known for their ESIPT activity as well as their AIEE activity. Upon functionalization of the –OH group, the ESIPT process stopped for 71. An appearance of yellow fluorescence was observed in an EtOH–water (5/5, v/v, HEPES pH = 7.4) solution of 71 upon the addition of Hg²⁺ ions. This yellow color was generated due to the Hg²⁺-triggered hydrolysis of thiocarbonate to form an –OH group and activate the ESIPT process (Fig. 37). Sensor 71 has a detection limit of 55 nM.

Fig. 37 The chemical structures and proposed sensing mechanisms of 71 and 72.

Similarly, sensor 72¹²⁸ was designed based on the ESIPT phenomenon, where 2-(2′-hydroxyphenyl)benzothiazole also acted as a signaling unit and thiophosphate as a reaction site. Blocking of –OH group with thiophosphate deactivated the ESIPT process and turned off the emission. In a solution of CH₃CN/HEPES (1 : 4, v/v, 10 mM, pH = 7.4), 72 turned blue-emissive upon addition of Hg²⁺ ions. Removal of the thiophosphate group resulted in the formation of an –OH group (Fig. 37) which activated the ESIPT to give blue emission. With an LOD of 12 nM, 72 can be applied for the detection of Hg²⁺ at the cellular level.

In this section, we have successfully discussed Hg²⁺ sensors based on reactions, which are chemodosimetric in nature as they irreversibly detect the analyte. In comparison to heteroatom-containing ligand systems, reaction-based sensors are superior due to their excellent selectivity towards Hg²⁺ ions. All the summarised information about reaction-based sensors (48–72), is given in Table 3.

Table 3 A comparison of different reaction-based sensors (48–72) for Hg²⁺ detection

Compound	Medium	LOD	Type of sensing	Biological study
48	PBS buffer (pH = 7.4, containing 2% DMSO)	7.6 × 10^−9 M	Turn-on fluorescence	Done
49	EtOH–water (1 : 1, v/v)	1.03 × 10^−8 M	Turn-on fluorescence	NA
50	THF–water (1 : 1, v/v, PBS, pH = 8.5)	1.59 × 10^−8 M	Turn-on fluorescence	NA
51	THF–water (1 : 1, v/v)	3.1 × 10^−7 M	Turn-on fluorescence	NA
52	PBS–DMSO buffer (5 : 5, v/v 20 mM, pH = 7.4)	6.8 × 10^−8 M	Turn-on fluorescence and colorimetric	Done
53	Ethanol–HEPES buffer (1 : 1, v/v, pH = 7.4)	5.8 × 10^−9 M	Turn-on fluorescence	NA
54a	MeCN–water (1 : 1, v/v)	57 × 10^−9 M	Turn-on fluorescence	Done
54b	EtOH–H2O (2 : 8, v/v, pH = 7.4)	4.0 × 10^−8 M	Turn-on fluorescence	Done
54c	DMS–PBS buffer (1 : 99, v/v, pH = 7.4)	19.3 × 10^−9 M	Turn-on fluorescence	Done
55	THF–PBS buffer (1 : 1, v/v, pH = 7.4)	59 × 10^−9 M	Turn-on fluorescence	Done
56	PBS buffer	27 × 10^−9 M	Turn-on fluorescence	NA
57	HEPES buffer	0.12 × 10^−6 M	Turn-on fluorescence	NA
58	CH3CN–PBS buffer (3 : 7, v/v, 10.0 mM, pH = 7.4)	244 ppb	Turn off fluorescence	NA
59	HEPES buffer	NA	Turn-on fluorescence and colorimetric	Done
60	Ethanol–H2O (2 : 8, v/v 50 mM HEPES buffer solution, pH = 7.4)	3.2 × 10^−9 M	Turn-on fluorescence	Done
61	PBS buffer (1% CH3CN)	7.8 × 10^−9 M	Turn-on fluorescence	Done
62	PBS buffer	6.5 × 10^−9 M	Turn-on fluorescence	NA
63	HEPES buffer/DMSO (9 : 1, v/v, pH = 7.2)	70 × 10^−9 M	Turn-on fluorescence	Done
64	CH3CN/H2O (8 : 2, v/v, 0.1 M KClO4 buffer, pH = 7.34)	Nanomolar level	Turn-on fluorescence	Done
65	PBS/EtOH (9 : 1, v/v)	9.1 × 10^−9 M	Ratiometric fluorescence	Done
66	EtOH–water (2 : 8, v/v)	18.8 × 10^−9 M	Turn-on fluorescence	Done
67	MeCN–HEPES (1 : 9, v/v, pH = 7.2)	1.6 × 10^−9 M	Turn-on fluorescence	Done
68a	MeCN–water (3 : 7, v/v)	1.08 × 10^−6 M	Turn-on fluorescence	Done
68b	DMSO–water (1 : 9, v/v)	8.1 × 10^−9 M	Colorimetric	NA
69	PBS buffer	300 × 10^−12 M	Turn-on fluorescence	Done
70	HEPES buffer	40 × 10^−9 M	Turn-on fluorescence	NA
71	EtOH–water (5/5, v/v, HEPES pH = 7.4)	55 × 10^−9 M	Turn-on fluorescence	NA
72	CH3CN–HEPES (10 mM, 1 : 4, v/v)	12 × 10^−9 M	Turn-on fluorescence	Done

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2.4 Polymer-based sensors for the detection of Hg²⁺

Above we have discussed small-molecule systems to detect Hg²⁺ ion in environmental sources and biological systems. Among the sensors (1–72), only a few compounds can detect Hg²⁺ in pure water or buffer medium. To overcome this issue, polymeric sensors were introduced for this detection process. Not only their water solubility but also the presence of many repeating units throughout the backbone, means polymers can produce highly amplified intensity to which can be attributed their high sensitivity.^129–134 Due to these advantageous features, polymeric materials have been developed in recent times for the detection of analytes such as Hg²⁺. In this section, we are going to discuss some polymeric materials which were applied for the detection of Hg²⁺ ion under different conditions.

A dithioacetal-based conjugated polymeric sensor 73¹³⁵ was developed for detecting Hg²⁺ in THF medium with high selectivity and sensitivity. Initial green fluorescence turned into red emission upon the addition of Hg²⁺ to a solution of 73. The intramolecular charge transfer process was inhibited in the dithioacetal containing 73, but Hg²⁺ promoted deprotection of dithioacetal and the formation of –CHO group again triggered the ICT process to give red emission (Fig. 38). This visual color change of fluorescence for 73 can be used as a good tool for detecting Hg²⁺ with a detection limit of 1 μM.

Fig. 38 The chemical structures and proposed sensing mechanisms of 73 and 74.

Another polymeric sensor 74,¹³⁶ consisting of a hydrophilic segment and a functionalized BODIPY segment, was developed for the detection of Hg²⁺. A 4-amino phenol functionalized BDIPY unit used as the responsible site for Hg²⁺ sensing. Due to the water solubility of random polymer 74, it can detect Hg²⁺ in a pure water medium. The appearance of a brown color and intense green emission was observed after the addition of Hg²⁺ to the solution of 74. This drastic change in color and emission was due to the hydrolysis of the imine bond by Hg²⁺ and the formation of an aldehyde group (Fig. 38). Sensor 74 has an LOD of 1.10 μM.

Sensor 75¹³⁷ is a thermoresponsive diblock copolymer with colorimetric detection ability towards Hg²⁺ ions. Polymeric sensor 75 has an LCST value of ∼55 °C and is molecularly soluble in water. Below the LCST, PHPDEA units are exposed to water. Upon the addition of Hg²⁺, the exposed PHPDEA unit is hydrolyzed to form the strong electron-withdrawing group cyanide. With this formation of a strong –CN group (Fig. 39), the intramolecular charge transfer process was maximized and an obvious sudden color change to pink from yellow was observed. But above LCST, 75 was unable to detect Hg²⁺ ions as the HPDEA units were then inside the hydrophobic core of the multi-molecular micelles. Sensor 75 was demonstrated as an excellent highly selective tool for the detection Hg²⁺ colorimetrically with a detection limit of 0.03 mM.

Fig. 39 The chemical structures and sensing mechanisms of sensors 75, 76a, and 76b.

Further stimuli-responsive polymeric sensors 76a and 76b were developed for the detection of Hg²⁺ in a colorimetric way with pH-tunable sensitivity.¹³⁸ Sensor 76a was developed by the protection of the aldehyde group of the azo-polymer with ethanethiol and 76b was developed by the protection of the aldehyde of the azo-polymer with 3-marcaptopropionic acid. These azo-polymer derivatives can detect Hg²⁺ in a HEPES buffer solution of pH 7.4 in a colorimetric fashion. But, interestingly, 76a detected Hg²⁺ in ∼60 minutes and 76b in ∼15 minutes at pH = 7.4. So the deprotection of dithioacetal promoted by Hg²⁺ was 4 times faster in the case of 76b compared to 76a due to the formation of C=O⋯Hg interaction, which further triggered the C⋯S–Hg cleavage which leads to aldehyde formation. But in the case of pH = 11, 76b showed a ∼60 minute reaction time in the presence of excess of Hg²⁺ ions, which suggested the pH-tunable sensitivity of the sensors. Ultimately the pH-dependent deprotection of dithioacetal was the main mechanism (Fig. 39) for the colorimetric detection ability of both sensors (76a and 76b).

A set of sensors 77a and 77b were developed as PEGylated BODIPY polymers.¹³⁹ The presence of a dithia-dioxa-aza cyclopentadecane ligand to the BODIPY core triggered the ICT process and both sensors were non-emissive. Due to the presence of PEG units, 77a and 77b can be used for the detection of Hg²⁺ ions in pure water (Fig. 40). In the presence of Hg²⁺, a drastic change in color and enhanced fluorescence were observed in both 77a and 77b. A yellow emission with a pink color to the naked eye for 77a and red emission with blue color to the naked eye for 77b were observed in the presence of Hg²⁺. Complexation of Hg²⁺ with the dithia-dioxa-aza cyclopentadecane ligand leads to the color and emission change. Due to the intense and bright emissive nature of 77a and 77b, they can be used at the cellular level to detect Hg²⁺ ions. The LOD value for 77a is 8.1 ppb and that for 77b is 129.3 ppb.

Fig. 40 The chemical structures of 77a and 77b.

A tryptophan-dithiocarbamate-based fluorogenic polymeric probe 78¹⁴⁰ was developed for the selective detection and removal of Hg²⁺ ions. In pure aqueous medium, 78 was able to detect Hg²⁺ by an enhancement in fluorescence signal at 366 nm due to the inhibition of the PET process. Due to the presence of a dithiocarbamate unit, it can bind the Hg²⁺ ion and stop the PET process to give the fluorescence signal (Fig. 41). With a detection limit of 1.5 nM, sensor 78 is able to detect Hg²⁺ at the cellular level. Another water-soluble copolymer 79¹⁴¹ was developed with a tryptophan unit and a pyridine segment attached through an imine bond. Due to the complexation of Hg²⁺ through the N atoms of the imine bond and pyridine units, quenching of fluorescence was observed (Fig. 41). This quenched fluorescence of 79 was used to detect Hg²⁺ ions at the cellular level with an LOD value of 7.41 nM.

Fig. 41 The chemical structures and proposed sensing mechanisms of 78 and 79.

Another BODIPY-based thiosemicarbazone moiety containing polymeric sensor 80a^142a was developed for detecting Hg²⁺ ions in a pure aqueous (HEPES buffer solution, pH = 7.4) medium. Upon the addition of Hg²⁺, a solution of 80a showed yellow emission from fluorescence-off mode. The binding of Hg²⁺ ions with two thiosemicarbazone groups of nearby polymeric chains stopped the C=N isomerization and resulted in a yellow fluorescence (Fig. 42). Complexation of Hg²⁺ with 80a resulted in a precipitate to remove Hg²⁺ successfully from the contaminated water source. Highly selective polymeric sensor 80a has a detection limit of 0.36 μM and the capability to remove mercury.

Fig. 42 The chemical structures of 80a and 80b + Hg²⁺ complex.

For the first time a chitosan thiomer, 80b^142b has been synthesized successfully and applied for the colorimetric detection of Hg²⁺ in aqueous solution. As Hg²⁺ has strong affinity towards thiol groups, 80b turned out to be an excellent binding material for it. Due to the formation of an S–Hg–S bond (Fig. 42), a drastic change in colour is observed from colorless to yellow to light brown to brown. This polymeric material has also been applied for removal of Hg²⁺ ions due to strong binding. Polymer 80b has been developed as an excellent sensor material with an ultra-low LOD of 0.465 ppb.

In this section, we have discussed polymeric sensors for the detection of Hg²⁺ ions. In recent years polymeric sensors have been developed to treat the analyte in pure water, which can be achieved by the synthesis of functionalized polymers with hydrophilic and hydrophobic segments. A summary of the information about polymeric sensors (73–80b) is given in Table 4.

Table 4 A comparison of different polymer-based sensors (73–80b) for Hg²⁺ detection

Compound	Medium	LOD	Type of sensing	Biological study
73	THF	1 × 10^−6 M	Turn-on fluorescence	NA
74	Pure water	1.1 × 10^−6 M	Turn-on fluorescence	NA
75	Water	0.03 × 10^−3 M	Colorimetric	NA
76a and 76b	Pure water	NA	Colorimetric	NA
77a	Pure water	8.1 ppb	Turn-on fluorescence and colorimetric	Done
77b	Pure water	129.3 ppb	Turn-on fluorescence and colorimetric	Done
78	Pure water	1.5 × 10^−9 M	Turn-on fluorescence	Done
79	Pure water	7.41 × 10^−9 M	Turn-off fluorescence	Done
80a	HEPES buffer	0.37 × 10^−6 M	Turn-on fluorescence	NA
80b	Aqueous medium	0.465 ppb	Colorimetric	NA

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We have now discussed the development and implementation of different types of detection systems based on heteroatom-containing ligand systems, reaction-based systems, and polymeric systems, for sensing Hg²⁺ ion in various sources.

3. Fluorescent and colorimetric detection systems for As(III)

The most toxic form of arsenic is the +3-oxidation state. In groundwater, arsenic exists as arsenite (As(III)) and arsenate (As(V)), though the arsenite form is more toxic than As(V). Except for conventional methods, rapid detection techniques using color change or emission change are very rare in number. In this section, we are going to discuss some of the chemical sensors which have been used to detect As(III) in a colorimetric way or a fluorometric way.

A combination of boron trifluoride diethyletherate ((C₂H₅)₂OBF₃) and curcumin produced sensor 81¹⁴³ for the selective detection of As(III) colorimetrically. A solution of 81 in 60% ethanol showed an orange color, but upon addition of As(III), it turned blue. This redshift in absorbance spectra was observed due to the deprotonation of the hydroxyl groups by As(III) to promote the delocalization of the negative charges towards the acceptor part (Fig. 43). This prominent change in color in the presence of As(III) can be used for the selective detection of As(III) with an LOD of 0.26 μM. Amberlite XAD-2 resin coated with 81 was used for the detection of As(III) in a solid phase with an LOD of 3 × 10⁻⁵ M.

Fig. 43 The chemical structures and proposed sensing mechanisms of 81, 82a, and 82b.

Two isatin-appended Schiff bases 82a and 82b¹⁴⁴ were developed for the colorimetric detection of As(III). DMSO solutions of 82a and 82b showed a brown color but upon adding AsO₂⁻, they turned blue with absorption maxima of 600 nm and 624 nm, respectively. The formation of a charge-transfer complex between As(III) and 82a/82b resulted in the changed colors. For both sensors As(III) was bound through C=O and C=N segments, as depicted in Fig. 43. In a colorimetric fashion, 82a and 82b can be used as selective sensors for As(III) detection with detection limits of 0.26 ppm and 0.56 ppm.

Sensor 83,¹⁴⁵ a combination of 2,6-diformyl-p-cresol and 4-aminoantipyrine was developed for the selective detection of arsenite in colorimetric and fluorometric fashion. A HEPES buffer (1 mM, pH 7.4; water/DMSO (v/v), 9 : 1) solution of 83 showed no color and no emission due to the strong PET effect originating from the hydroxyl group. Addition of AsO₃³⁻ ions to the solution of 83 produced a light-yellow greenish color and green emission. This drastic and prominent change in color and emission was the result of the binding of arsenite with 83, which disturbed the PET process and triggered the CHEF process via intermolecular hydrogen bonding (Fig. 44). Its turn-on fluorescence feature was used effectively for intracellular tracking of arsenite. The dual-mode sensing process and excellent LOD value of 4.12 made 83 a potential tool in the field of rapid and effective arsenite detection.

Fig. 44 The chemical structure and proposed sensing mechanism of sensor 83.

Condensation between rhodamine 6G hydrazide and 5-methyl salicylaldehyde produced sensor 84.¹⁴⁶ In acetonitrile : HEPES buffer (4 : 1, v/v, pH 7.4) solution, 84 did not show any color or emission due to the spirolactam ring-closed form. After the addition of As(III), a solution of 84 turned pink in color with an intense yellow emission. Spirolactam ring-opening followed by strong 1 : 1 binding between As(III) and 84 resulted in the observed color and emission change (Fig. 45). Due it turn-on fluorescence, 84 was also used for detecting As(III) at the cellular level. Dual-channel sensor 84 emerged as an excellent material for the selective detection of As(III) with an LOD of 0.164 ppb.

Fig. 45 The chemical structures of 84 and 85 along with the proposed sensing mechanism of 84.

An aggregation-induced emission-based sensor 85 was developed using tetraphenylethene (TPE) as a fluorescent moiety and cysteine as a binding ligand for As(III).¹⁴⁷ An aqueous solution (THF–water, 1 : 99, v/v) of 85 (Fig. 45) was nonfluorescent, but upon addition of As(III) an intense blue fluorescence was observed and it gradually became more intense with an increasing concentration of As(III). Binding of As(III) with the –SH group of cysteine of 85 through the formation of As–S bond promoted the π–π stacking of TPE units to produce the intense blue emission which is typical of the AIE process. Sensor 85 has a detection limit of 0.5 ppb, which is much lower than the WHO limit.

An oxime-based fluorogenic probe 86¹⁴⁸ was applied for the detection of arsenite with turn-on fluorescence. In a pure aqueous medium of pH 7.24, 86 did not show any prominent fluorescence signal, but upon the introduction of AsO₂⁻ a strong blue emission was observed. This turn-on fluorescence signal helped to detect AsO₂⁻ in pure aqueous medium with a detection limit of 1.32 μM. The output fluorescence signal was the result of H-bonding interaction between AsO₂⁻ and 86 (Fig. 46). This H-bonding interaction leads to the formation of different nano/microstructures in pure aqueous solution. Sensor 86 was successfully utilized for cell imaging in the presence of AsO₂⁻ ions. This sensor suffered from a selectivity issue, as it showed similar fluorescence properties in the presence of arsenate as well. Along with the sensitivity issue, the LOD value of 86 towards AsO₂⁻ is not up to the mark compared to the WHO level.

Fig. 46 The chemical structures and proposed sensing mechanisms of 86 and 87.

A colorimetric probe 87 was designed as a benzothiazole Schiff base for the highly sensitive and selective detection of As³⁺ ions.¹⁴⁹ Sensor 87 showed a light yellow color in DMSO–water (1 : 1) medium. After the addition of As³⁺ ions, a solution of 87 turned brownish orange. Due to strong 1 : 1 binding between 87 and As³⁺ (Fig. 46), a strong change in color was observed. But unfortunately, the same characteristics were observed when 87 was treated with As⁵⁺ with the same absorbance spectrum. Though the drastic change in color was helpful for recognizing As³⁺ ions, the selectivity issue was a drawback for this system. It can be used for detecting arsenic (As³⁺/As⁵⁺) in water but cannot be used for the selective detection of As³⁺. Sensor 87 suffered from selectivity issues, but the detection limit was excellent with an LOD value of 7.2 ppb for As³⁺ ions.

A chromogenic–fluorescence probe 88¹⁵⁰ was applied for the detection of As³⁺ along with Cr³⁺, Fe³⁺, Al³⁺, Ga³⁺, and In³⁺ ions. In a water–MeCN (95 : 5, v/v) solution, in the presence of As³⁺, the color of 88 changed to violet from colorless along with a quenching of fluorescence. For all other trivalent cations as well, the same observation was found. It was hypothesized that cation-induced dehydration formed a highly conjugated cationic molecule and that led to the color change (Fig. 47). Sensor 88 has LODs of 10.4 μM (UV-vis) and 10.7 μM (fluorescence). Though the color change is drastic in the case of 88, it suffered from low selectivity towards As³⁺ and a low detection limit. Due to these issues, 88 cannot be used to separately detect As³⁺ ions. Similarly, another sensor 89 was developed by the combination of 2-hydroxy-1-naphthaldehyde and thiosemicarbazide.¹⁵¹ With no color or emission in DMF–water (9 : 1, v/v, HEPES, pH = 7.2), 89 changed its color to yellow with a unique emission at 495 nm upon addition of AsO₂⁻ ions. A strong hydrogen bonding interaction between AsO₂⁻ and the –OH and –NH groups of 89 leads to a color and emission change (Fig. 47). Eventually, 89 could be a useful sensor with an LOD value of 66 nM but it suffers from the selectivity issue as it can also detect CN⁻ ions with the same spectroscopic properties.

Fig. 47 The chemical structures and proposed sensing mechanisms of sensors 88 and 89.

Another hydrazine-based thiocarbamide chemosensor 90 was applied for the colorimetric and fluorometric detection of AsO₃³⁻ ions.¹⁵² Sensor 90 detected AsO₃³⁻ ions in MeCN–water (9 : 1, v/v, pH = 7.2) by changing the color from colorless to yellow and non-fluorescent to yellow fluorescence. Here also the H-bonding interaction between the anion, the –NH group of thiocarbamide segment, and the Ar–OH group was the reason behind the change in color as well as in fluorescence (Fig. 48). The dual-sensing properties of 90 with an excellent detection limit of 15 nM meant it emerged as a good tool for detecting As(III) in real applications as it was able to detect the analyte in contaminated real samples. It can also detect phosphate ions with the same color and emission change as AsO₃³⁻, so there might be interference.

Fig. 48 The chemical structures of 90 and 91 along with the proposed sensing mechanism of 91.

Another fluorogenic probe 91 was designed by the combination of pyrene and calix[4]arene for detecting As³⁺.¹⁵³ Due to the presence of an amide group in the system, it can be a catalysis binding site as well as helping the CHEF process. In the presence of As³⁺ ions, the fluorescence intensity of 91 decreased, as a result of binding between the sensor and analyte for activation of the PET process (Fig. 48). This turn-off fluorescence of 91 was used to analyze real samples contaminated by As³⁺, as the sensor has an LOD value of 11.53 nM for As³⁺. Besides the excellent sensitivity of 91 towards As³⁺, selectivity was a problem as the sensor was able to detect Nd³⁺ and Br⁻ by turn-on and turn-off fluorescence, respectively, under the same experimental conditions.

A colorimetric sensor 92 was developed with condensation between 2,4-dinitrophenyl hydrazine and 2,4-dihydroxy benzaldehyde.¹⁵⁴ Due to the presence of 2,4-dinitrophenyl hydrazine, it can act as an H-bonding formation segment with some unique chromophoric features. Sensor 92 (Fig. 49) showed different colors in water–DMSO (9 : 1) and water–MeCN (9 : 1) mixtures. The color of 92 in water–DMSO solution changed to purple from orange in the presence of As³⁺ but in the case of a water–MeCN solution, it changed from yellow to red. The presence of Ar–OH and –NH groups in the sensor was attributed to the strong bonding of As³⁺ by H-bonding interaction which resulted in a drastic and intense color change. So, sensor 92 can serve as a good naked-eye sensor with high selectivity and an LOD value of 0.35 × 10⁻⁶ M for As³⁺ ions.

Fig. 49 The chemical structures of 92, 93, and 94, and the proposed sensing mechanisms of 93 and 94.

Two coumarin-based sensors 93¹⁵⁵ and 94¹⁵⁶ were designed as coumarin-appended benzothiazolines for the detection of As(III) in organic media. Both sensors were able to detect As(III) in THF medium by turn-on fluorescence. It was expected that As(III) coordination with the Schiff-base thiolate form of the sensors followed by the formation of benzothiazole was the reason behind the turning on of emission in both cases (Fig. 49). Both sensors were able to detect As(III) with high selectivity in pure THF medium. Sensor 94 was able to sense inorganic As(III) with an LOD value of 0.14 ppb. Similarly, sensor 93 was also extremely sensitive towards As(III) with a detection limit of 0.24 ppb. But both sensors were able to sense As(III) in an organic medium, which could be a drawback for them.

A norbornene-derived monomer 95a and its homopolymer 95b were developed for detecting As(III), where rhodamine B was used as the signaling unit.¹⁵⁷ Both the monomer and polymer solution in methanol–water solution remained colorless as well as non-emissive due to the spirolactam ring-closed form of the rhodamine unit. In the presence of KIO₃ and HCl, the solution of 95a turned pink in color and reddish in emission due to the opening of the spirolactam ring. After the addition of As(III) solution, the pH changed from 1.34 to 4.23, and the color of the solution changed to brown, and the emission changed to greenish. In the presence of KIO₃ and HCl, As(III) oxidized to As(V) and generated I₂ in the solution. This I₂ further reacted with the double bond of the norbornene unit, and as a result, the color and fluorescence were changed (Fig. 50). A similar mechanism was followed by polymer 95b. The oxidation process was further supported by cyclic voltammetry which suggested that two-electron oxidation took place during the sensing process. Paper strips coated with polymer 95b were successfully used for the “in-field” detection of As(III) in water sources. So it is clear that 95a and 95b are unique for their selective detection of As(III) in both colorimetric and fluorometric processes in a novel mechanistic pathway. Sensor 95a has a detection limit of 200 nM for As(III) ions.

Fig. 50 The chemical structures of 95a and 95b along with the proposed sensing mechanism of 95a.

We have discussed reported chemical sensors for the detection of As(III) in different mediums with different mechanisms. Most of the sensors preferably interact with As(III) to produce a new signal for the identification of the analyte. All the information about sensors 81–95b is given in Table 5.

Table 5 A comparison of different sensors (81–95b) for As(III) detection

Compound	Medium	LOD	Type of sensing	Biological study
81	60% ethanol	3 × 10^−5 M	Colorimetric	NA
82a	DMSO	0.26 ppm	Colorimetric	NA
82b	DMSO	0.56 ppm	Colorimetric	NA
83	Water–DMSO (9 : 1, v/v, pH = 7.4)	4.12 ppb	Colorimetric and turn-on fluorescence	NA
84	MeCN–HEPES (4 : 1, v/v, pH = 7.4)	0.164 ppb	Colorimetric and turn-on fluorescence	Done
85	THF–water (1 : 99, v/v)	0.5 ppb	Turn-on fluorescence	NA
86	Pure aq. medium	1.32 × 10^−6 M	Turn-on fluorescence	Done
87	DMSO–water (1 : 1, v/v)	7.2 ppb	Colorimetric	NA
88	Water–MeCN (95 : 5, v/v)	10.4 × 10^−6 M (UV), 10.7 × 10^−6 M (FL)	Colorimetric and turn-on fluorescence	NA
89	DMF–water (9 : 1, v/v, HEPES, pH = 7.2)	66 × 10^−9 M	Colorimetric and turn-on fluorescence	NA
90	MeCN–water (9 : 1, v/v, pH = 7.2)	15 × 10^−9 M	Turn-on fluorescence and colorimetric	NA
91	MeCN–PBS (8 : 2, v/v, pH = 7.2)	11.53 × 10^−9 M	Turn-off fluorescence	NA
92	Water–DMSO (9 : 1, v/v)	0.35 × 10^−6 M	Colorimetric	NA
93	THF	0.24 ppb	Turn-on fluorescence	NA
94	THF	0.14 ppb	Turn-on fluorescence	NA
95a	MeOH–water	200 × 10^−9 M	Colorimetric and turn-on fluorescence	NA

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4. Conclusions and perspectives

Due to the toxic extent of Hg²⁺ and As(III) in humans and in different biological systems, these ions have received extensive interest from researchers with the aim of creating detection tools. The initial section of our review covered reported colorimetric and fluorescence sensors for Hg²⁺ developed after 2015. Recognition of Hg²⁺ ions was achieved successfully by ligand-based systems and rhodamine systems; many of the systems suffered from selectivity issues, but most of them are reversible. This reversible nature can be used for the reuse of the sensor for detection purposes, which is a great advantage. These selectivity issues have been overcome by the development of reaction-based sensor systems where Hg²⁺-mediated new molecule formation leads to output signals. Unfortunately, most of the small molecule sensors we have discussed here suffer from low solubility in water. Despite the solubility issues, many of these have excellent sensitivity, with LOD values lower than the permissible concentration of Hg²⁺ set by the EPA/WHO. However, solubility issues have been taken care of by introducing polymeric materials, where different hydrophilic segments were used to increase the water solubility of the sensors. Despite the water solubility of the polymeric materials, the sensitivity of these sensors is not up to the mark compared to small molecular sensors. Many of the discussed sensors were able to successfully track Hg²⁺ ions in biological systems with a distinct emission change, which is a new development in the field of mercury sensors. Apart from Hg²⁺, some of the sensors discussed here can detect CH₃Hg⁺ in both environmental samples and biological systems, which is an impressive development and opens up a new area for the design and development of new sensors. On the other hand, the development of As(III) ion sensors is still very rare due to their complicated chemical behavior. We have tried to cover most of the available chemical sensors for As(III) in this review. Most of the sensors for As(III) are based on H-bonding interactions, which leads to a color change or fluorescence change. Unfortunately, most of the discussed sensors suffer from interference from other trivalent metal ions or anions with the same output signal. This interference is harsh in the case of the distinct identification of As(III), either in cationic form or in anionic form. Apart from the selectivity viewpoint, most of the sensors have a detection limit way below the WHO/EPA guidelines.

For both toxic ions, different new methods have been developed in the last decade with new strategies, new applications, etc. We believe that in the case of Hg²⁺ ion detection, polymeric sensors can evolve as an excellent system due to their many advantages, such as signal amplification (as many repeating units are present), water solubility, and the stability of the probes. The detection limits should be improved for better implementation of “in-field” applications of polymeric materials. On the other hand, in the area of As(III) detection, there is a huge chance for improvement with respect to the design and development of sensors. For a more useful toolkit for As(III) detection, highly selective and sensitive sensors are in high demand to date. More and more development of polymeric sensors for As(III) detection is needed for device fabrication to provide a permanent solution for societies that are greatly affected by arsenic poisoning.

List of abbreviations

LED	Light-emitting diode
DMF	Dimethylformamide
DMSO	Dimethyl sulfoxide
THF	Tetrahydrofuran
UV-vis	Ultraviolet-visible
LCST	Lower critical solution temperature
HEPES	4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid
PBS	Phosphate-buffered saline
BODIPY	Boron-dipyrromethene
NBD	7-Nitrobenz-2-oxa-1,3-diazole
NIR	Near-infrared
ICT	Intramolecular charge transfer
PET	Photoinduced electron transfer
FRET	Förster resonance energy transfer
ESIPT	Excited-state intramolecular proton transfer
AIEE	Aggregation induced enhanced emission
AIE	Aggregation induced emission
CHEF	Chelation-enhanced fluorescence
TICT	Twisted intramolecular charge transfer

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

T. S. thanks IISER Kolkata for a research fellowship. R. S. thanks DST, DBT, IISER Kolkata for funding. T. S. and R. S. thank IISER Kolkata for infrastructure support.

References

1. G. Banfalvi, Cellular Effects of Heavy Metals, Springer, Netherlands, London, New York, 2011.
2. N. Herawati, S. Suzuki, K. Hayashi, I. F. Rivai and H. Koyoma, Cadmium, copper and zinc levels in rice and soil of Japan, Indonesia and China by soil type, Bull. Environ. Contam. Toxicol., 2000, 64, 33–39.
3. S. Sarkar and R. Shunmugam, Unusual redshift of the sensor while detecting the presence of Cd²⁺ in aqueous environment, ACS Appl. Mater. Interfaces, 2013, 5, 7379–7383.
4. W. Salomons, U. Forstner and P. Mader, Heavy Metals: Problems and Solutions, Springer-Verlag, Berlin, Germany, 1995.
5. S. Bhattacharya, V. N. Rao, S. Sarkar and R. Shunmugam, Unusual emission from norbornene derived phosphonate molecule-a sensor for Fe^III in aqueous environment, Nanoscale, 2012, 4, 6962–6966.
6. World Health Organization, Guidelines for drinking-water quality, Geneva, 3rd edn, 2004, vol. 1, p. 188.
7. P. B. Tchounwou, C. G. Yedjou, A. K. Patlolla and D. J. Sutton, Heavy metal toxicity and the environment, Molecular, clinical and environmental toxicology, Springer, Basel, 2012, pp. 133–164.
8. (a) J. C. Saha, A. K. Dikshit, M. Bandyopadhyay and K. C. Saha, A review of arsenic poisoning and its effects on human health, Crit. Rev. Environ. Sci. Technol., 1999, 29, 281–313; (b) K. Christen, Environ. Sci. Technol, 2001, 35, 184–185.
9. S. Kapaj, H. Peterson, K. Liber and P. Bhattacharya, Human Health Effects from Chronic Arsenic Poisoning – A Review, J. Environ. Sci. Health, Part A: Toxic/Hazard. Subst. Environ. Eng., 2006, 41, 2399–2428.
10. K. S. M. Abdul, S. S. Jayasinghe, E. P. Chandana, C. Jayasumana and P. M. C. De Silva, Arsenic and human health effects: A review, Environ. Toxicol. Pharmacol., 2015, 40, 828–846.
11. A. H. Smith, C. Hopenhayn-Rich, M. N. Bates, H. M. Goeden, I. Hertz-Picciotto, H. M. Duggan, R. Wood, M. J. Kosnett and M. T. Smith, Cancer risks from arsenic in drinking water, Environ. Health Perspect., 1992, 97, 259–267.
12. W. R. Cullen and K. J. Reimer, Arsenic speciation in the environment, Chem. Rev., 1989, 89, 713–764.
13. N. Bhandari, R. J. Reeder and D. R. Strongin, Photoinduced oxidation of arsenite to arsenate in the presence of goethite, Environ. Sci. Technol., 2012, 46, 8044–8051.
14. United States Environmental Protection Agency Arsenic and Clarifications to Compliance and New Source Monitoring Rule: A Quick Reference Guide, EPA 816-F-01-004, US EPA, Wasington, D.C., 2001.
15. B. Weiss, Why methylmercury remains a conundrum 50 years after Minamata, Toxicol. Sci, 2007, 97, 223–225.
16. L. Amin-Zaki, S. Elhassani, M. A. Majeed, T. W. Clarkson, R. A. Doherty and M. Greenwood, Intra-uterine methylmercury poisoning in Iraq, Problems of Birth Defects, Springer, Dordrecht, 1974, pp. 233–241.
17. F. Di Natale, A. Lancia, A. Molino, M. Di Natale, D. Karatza and D. Musmarra, Capture of mercury ions by natural and industrial materials, J. Hazard. Mater., 2006, 132, 220–225.
18. W. F. Fitzgerald, C. H. Lamborg and C. R. Hammerschmidt, Marine biogeochemical cycling of mercury, Chem. Rev., 2007, 107, 641.
19. T. W. Clarkson, L. Magos and G. J. Myers, The toxicology of mercury-current exposures and clinical manifestations, N. Engl. J. Med., 2003, 349, 1731–1737.
20. R. Von Burg, Inorganic mercury, J. Appl. Toxicol., 1995, 15, 483–493.
21. R. Shunmugam, G. J. Gabriel, C. E. Smith, K. A. Aamer and G. N. Tew, A highly selective colorimetric aqueous sensor for mercury, Chem. – Eur. J., 2008, 14, 3904–3907.
22. J. Chen, J. Pan and S. Chen, A Naked-Eye Colorimetric Sensor for Hg²⁺ Monitoring with Cascade Signal Amplification Based on Target Induced Conjunction of Split DNAzyme Fragments, Chem. Commun., 2017, 53, 10224–10227.
23. V. Iyengar and J. Woittiez, Trace elements in human clinical specimens: evaluation of literature data to identify reference values, Clin. Chem., 1988, 34, 474–481.
24. A. T. Townsend, K. A. Miller, S. McLean and S. Aldous, The determination of copper, zinc, cadmium and lead in urine by high resolution ICP-MS, J. Anal. At. Spectrom., 1998, 13, 1213–1219.
25. X. C. Le, M. Ma and N. A. Wong, Speciation of arsenic compounds using high-performance liquid chromatography at elevated temperature and selective hydride generation atomic fluorescence detection, Anal. Chem., 1996, 68, 4501–4506.
26. C. B’Hymer and J. A. Caruso, Arsenic and its speciation analysis using high-performance liquid chromatography and inductively coupled plasma mass spectrometry, J. Chromatogr. A, 2004, 1045, 1–13.
27. K. C. Thompson and R. J. Reynolds, Atomic Absorption. Fluorescence and Flame Emission Spectroscopy, Charles Griftin, London, 2nd edn, 1978, vol. 51, pp. 175–176.
28. J. L. Gomez-Ariza, D. Sánchez-Rodas, I. Giráldez and E. Morales, A comparison between ICP-MS and AFS detection for arsenic speciation in environmental samples, Talanta, 2000, 51, 257–268.
29. T. Nakazato and H. Tao, A high-efficiency photooxidation reactor for speciation of organic arsenicals by liquid chromatography – hydride generation – ICPMS, Anal. Chem., 2006, 78, 1665–1672.
30. M. Mulvihill, A. Tao, K. Benjauthrit, J. Arnold and P. Yang, Surface-enhanced Raman spectroscopy for trace arsenic detection in contaminated water, Angew. Chem., 2008, 120, 6556–6560.
31. H. M. Anawar, Arsenic Speciation in Environmental Samples by Hydride Generation and Electrothermal Atomic Absorption Spectrometry, Talanta, 2012, 88, 30–42.
32. W. Holak, Determination of Arsenic by Cathodic Stripping Voltammetry with a Hanging Mercury Drop Electrode, Anal. Chem., 1980, 52, 2189–2192.
33. S. S. Hassan, A. R. Sirajuddin, T. G. Solangi, M. S. Kazi, Y. Kalhoro, Z. Junejo, A. Tagar and N. H. Kalwar, Nafion Stabilized Ibuprofen-Gold Nanostructures Modified Screen Printed Electrode as Arsenic(III) Sensor, J. Electroanal. Chem., 2012, 682, 77–82.
34. Y. Zhou, Z. Xu and J. Yoon, Fluorescent and colorimetric chemosensors for detection of nucleotides, FAD and NADH: highlighted research during 2004–2010, Chem. Soc. Rev., 2011, 40, 2222–2235.
35. D. T. Quang and J. S. Kim, Fluoro-and chromogenic chemodosimeters for heavy metal ion detection in solution and biospecimens, Chem. Rev., 2010, 110, 6280–6301.
36. X. Chen, Y. Zhou, X. Peng and J. Yoon, Fluorescent and colorimetric probes for detection of thiols, Chem. Soc. Rev., 2010, 39, 2120–2135.
37. J. F. Zhang, Y. Zhou, J. Yoon and J. S. Kim, Recent progress in fluorescent and colorimetric chemosensors for detection of precious metal ions (silver, gold and platinum ions), Chem. Soc. Rev., 2011, 40, 3416–3429.
38. E. M. Nolan and S. J. Lippard, Tools and tactics for the optical detection of mercuric ion, Chem. Rev., 2008, 108, 3443–3480.
39. H. N. Kim, W. X. Ren, J. S. Kim and J. Yoon, Fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions, Chem. Soc. Rev., 2012, 41, 3210–3244.
40. G. Chen, Z. Guo, G. Zeng and L. Tang, Fluorescent and colorimetric sensors for environmental mercury detection, Analyst, 2015, 140, 5400–5443.
41. M. B. Gumpu, S. Sethuraman, U. M. Krishnan and J. B. B. Rayappan, A review on detection of heavy metal ions in water–an electrochemical approach, Sens. Actuators, B, 2015, 213, 515–533.
42. M. Mulvihill, A. Tao, K. Benjauthrit, J. Arnold and P. Yang, Surface-enhanced Raman spectroscopy for trace arsenic detection in contaminated water, Angew. Chem., Int. Ed., 2008, 47, 6456–6460.
43. J. Hao, M. J. Han, S. Han, X. Meng, T. L. Su and Q. K. Wang, SERS detection of arsenic in water: A review, J. Environ. Sci., 2015, 36, 152–162.
44. E. Priyadarshini and N. Pradhan, Gold nanoparticles as efficient sensors in colorimetric detection of toxic metal ions: a review, Sens. Actuators, B, 2017, 238, 888–902.
45. M. Li, H. Gou, I. Al-Ogaidi and N. Wu, Nanostructured sensors for detection of heavy metals: a review, ACS Sustainable Chem. Eng., 2013, 1, 713–723.
46. L. Farzin, M. Shamsipur and S. Sheibani, A review: Aptamer-based analytical strategies using the nanomaterials for environmental and human monitoring of toxic heavy metals, Talanta, 2017, 174, 619–627.
47. A. Maity, A. Sil, S. Nad and S. K. Patra, A highly selective, sensitive and reusable BODIPY based ‘OFF/ON'fluorescence chemosensor for the detection of Hg²⁺ Ions, Sens. Actuators, B, 2018, 255, 299–308.
48. C. B. Bai, P. Xu, J. Zhang, R. Qiao, M. Y. Chen, M. Y. Mei, B. Wei, C. Wang, L. Zhang and S. S. Chen, Long-Wavelength Fluorescent Chemosensors for Hg²⁺ based on Pyrene, ACS Omega, 2019, 4, 14621–14625.
49. A. Kumar, R. Ananthakrishnan, G. Jana, P. K. Chattaraj, S. Nayak and S. K. Ghosh, An Intramolecular Charge Transfer Induced Fluorescent Chemosensor for Selective Detection of Mercury (II) and its Self-Turn-On Inside Live Cells at Physiological pH, ChemistrySelect, 2019, 4, 4810–4819.
50. B. Muzey and A. Naseem, An AIEE active 1, 8-naphthalimide-sulfamethizole probe for ratiometric fluorescent detection of Hg²⁺ ions in aqueous media, J. Photochem. Photobiol., A, 2020, 391, 112354.
51. Y. Yuan, X. Chen, Q. Chen, G. Jiang, H. Wang and J. Wang, New switch on fluorescent probe with AIE characteristics for selective and reversible detection of mercury ion in aqueous solution, Anal. Biochem., 2019, 585, 113403.
52. T. P. Yoon and E. N. Jacobsen, Privileged chiral catalysts, Science, 2003, 299, 1691–1693.
53. A. Dalla Cort, P. De Bernardin, G. Forte and F. Y. Mihan, Metal–salophen-based receptors for anions, Chem. Soc. Rev., 2010, 39, 3863–3874.
54. K. Liu, Y. Zhang, T. Zhou, X. Liu, B. Chen, X. Wang, X. Zhao, J. Huo, Y. Wang and B. Zhu, Sequential recognition of Hg²⁺ and I⁻ based on a novel BODIPY-salen sensor, Sens. Actuators, B, 2017, 253, 1194–1198.
55. N. Dey, J. Kulhanek, F. Bures and S. Bhattacharya, J. Org. Chem., 2019, 84, 1787–1796.
56. Y. Li, W. Shi, J. Ma, X. Wang, X. Kong, Y. Zhang, L. Feng, Y. Hui and Z. Xie, A novel optical probe for Hg²⁺ in aqueous media based on mono-thiosemicarbazone Schiff base, J. Photochem. Photobiol., A, 2017, 338, 1–7.
57. A. Kumar and N. Ahmed, Indirect Approach for CN–Detection: Development of “Naked-Eye” Hg²⁺-Induced Turn-Off Fluorescence and Turn-On Cyanide Sensing by the Hg²⁺ Displacement Approach, Ind. Eng. Chem. Res., 2017, 56, 6358–6368.
58. K. M. Vengaian, C. D. Britto, K. Sekar, G. Sivaraman and S. Singaravadivel, Phenothiazine-diaminomalenonitrile based Colorimetric and Fluorescence “Turn-off-on” Sensing of Hg²⁺ and S²⁻, Sens. Actuators, B, 2016, 235, 232–240.
59. L. N. Neupane, P. K. Mehta, J. U. Kwon, S. H. Park and K. H. Lee, Selective red-emission detection for mercuric ions in aqueous solution and cells using a fluorescent probe based on an unnatural peptide receptor, Org. Biomol. Chem., 2019, 17, 3590–3598.
60. M. L. Presti, R. Martínez-Máñez, J. V. Ros-Lis, R. M. Batista, S. P. Costa, M. M. M. Raposo and F. Sancenón, A dual channel sulphur-containing a macrocycle functionalised BODIPY probe for the detection of Hg (II) in a mixed aqueous solution, New J. Chem., 2018, 42, 7863–7868.
61. A. K. Jha, S. Umar, R. K. Arya, D. Datta and A. Goel, Pyrano [3, 2-c] julolidin-2-ones: a novel class of fluorescent probes for ratiometric detection and imaging of Hg 2+ in live cancer cells, J. Mater. Chem. B, 2016, 4, 4934–4940.
62. R. X. Zhang, P. F. Li, W. J. Zhang, N. Li and N. Zhao, A highly sensitive fluorescent sensor with aggregation-induced emission characteristics for the detection of iodide and mercury ions in aqueous solution, J. Mater. Chem. C, 2016, 4, 10479–10485.
63. A. Tang, Z. Chen, D. Deng, G. Liu, Y. Tu and S. Pu, Aggregation-induced emission enhancement (AIEE)-active tetraphenylethene (TPE)-based chemosensor for Hg²⁺ with solvatochromism and cell imaging characteristics, RSC Adv., 2019, 9, 11865–11869.
64. S. Gharami, K. Aich, P. Ghosh, L. Patra, N. Murmu and T. K. Mondal, A fluorescent “ON–OFF–ON” switch for the selective and sequential detection of Hg²⁺ and I⁻ with applications in imaging using human AGS gastric cancer cells, Dalton Trans., 2020, 49, 187–195.
65. Y. F. Xiao, L. Yu and B. Quan, A highly selective and sensitive fluorescein-based chemodosimeter for Hg²⁺ ions in aqueous media, Anal. Chim. Acta, 2007, 584, 95–100.
66. K. M. K. Swamy, K. K. Soo, L. N. Ha, K. S. M. Shantha, K. S. Jong and Y. Juyoung, Fluorescent sensing of pyrophosphate and ATP in 100% aqueous solution using a fluorescein derivative and Mn²⁺, Tetrahedron Lett., 2007, 48, 8683–8686.
67. K. J. Hee, P. E. Ji, C. G. Myung, A. Sangdoo and C. K. Suk, Selective chromogenic and fluorogenic signalling of Hg²⁺ ions using a fluorescein-coumarin conjugate, Dyes Pigm., 2010, 84, 54–58.
68. P. Piyanuch, S. Watpathomsub, V. S. Lee, H. A. Nienaber and N. Wanichacheva, Highly sensitive and selective Hg²⁺-chemosensor based on dithia-cyclic fluorescein for optical and visual-eye detections in aqueous buffer solution, Sens. Actuators, B, 2016, 224, 201–208.
69. R. V. Rathod, S. Bera, P. Maity and D. Mondal, Mechanochemical Synthesis of a Fluorescein-Based Sensor for the Selective Detection and Removal of Hg²⁺ Ions in Industrial Effluents, ACS Omega, 2020, 5, 4982–4990.
70. H. Mohammad, A. S. M. Islam, C. Prodhan and M. Ali, A fluorescein-based chemosensor for “turn-on” detection of Hg²⁺ and the resultant complex as a fluorescent sensor for S²⁻ in semi-aqueous medium with cell-imaging application: experimental and computational studies, New J. Chem., 2019, 43, 5297–5307.
71. N. Kaur, G. Jindal and S. Kumar, Cascade recognition of Hg²⁺ and cysteine using a naphthalene based ESIPT sensor and its application in a set/reset memorized device, New J. Chem., 2019, 43, 436–443.
72. J. Wang, Q. Rao, H. Wang, Q. Zhang, G. Liu, Z. Wu, J. Yu, X. Zhu, Y. Tian and H. Zhou, A terpyridine-based test strip for the detection of Hg²⁺ in various water samples and drinks, Anal. Methods, 2019, 11, 227–231.
73. P. G. Sutariya, H. Soni, S. A. Gandhi and A. Pandya, Luminescent behavior of pyrene-allied calix [4] arene for the highly pH-selective recognition and determination of Zn²⁺, Hg²⁺ and I⁻ via the CHEF-PET mechanism: computational experiment and paper-based device, New J. Chem., 2019, 43, 9855–9864.
74. T. Anand and S. K. Sahoo, Cost-effective approach to detect Cu (II) and Hg (II) by integrating a smartphone with the colorimetric response from a NBD-benzimidazole based dyad, Phys. Chem. Chem. Phys., 2019, 21, 11839–11845.
75. X. Cao, Y. Li, Y. Yu, S. Fu, A. Gao and X. Chang, Nanoscale, 2019, 11, 10911–10920.
76. D. Liu, H. Zhu, J. Shi, X. Deng, T. Zhang, Y. Zhao, P. Qi, G. Yang and H. He, A 1, 8-naphthalimide-based fluorescent sensor with high selectivity and sensitivity for Hg²⁺ in aqueous solution and living cells, Anal. Methods, 2019, 11, 3150–3154.
77. Y. Zhang, C. Zhang, Y. Wu, B. Zhao, L. Wang and B. Song, RSC Adv., 2019, 9, 23382–23389.
78. S. Srivastava, N. Thakur, A. Singh, P. Shukla, V. K. Maikhuri, N. Garg, A. Prasad and R. Pandey, Development of a fused imidazo [1,2-a] pyridine based fluorescent probe for Fe³⁺ and Hg²⁺ in aqueous media and HeLa cells, RSC Adv., 2019, 9, 29856–29863.
79. S. Sahana, G. Mishra, S. Sivakumar and P. K. Bharadwaj, A 2-(2′-hydroxyphenyl) benzothiazole (HBT)–quinoline conjugate: a highly specific fluorescent probe for Hg²⁺ based on ESIPT and its application in bioimaging, Dalton Trans., 2015, 44, 20139–20146.
80. F. Bu, B. Zhao, W. Kan, L. Ding, T. Liu, L. Wang, B. Song, W. Wang and Q. Deng, An ESIPT characteristic “turn-on” fluorescence sensor for Hg²⁺ with large Stokes shift and sequential “turn-off” detection of S²⁻ as well as the application in living cells, J. Photochem. Photobiol., A, 2020, 387, 112165.
81. L. Zong, C. Wang, Y. Song, Y. Xie, P. Zhang, Q. Peng, Q. Li and Z. Li, A dual-function probe based on naphthalene diimide for fluorescent recognition of Hg²⁺ and colorimetric detection of Cu²⁺, Sens. Actuators, B, 2017, 252, 1105–1111.
82. L. Zong, Y. Xie, Q. Li and Z. Li, A new red fluorescent probe for Hg²⁺ based on naphthalene diimide and its application in living cells, reversibility on strip papers, Sens. Actuators, B, 2017, 238, 735–743.
83. M. D. Gholami, S. Manzhos, P. Sonar, G. A. Ayoko and E. L. Izake, Dual chemosensor for the rapid detection of mercury (ii) pollution and biothiols, Analyst, 2019, 144, 4908–4916.
84. P. Wang, Y. An and J. Wu, Highly sensitive turn-on detection of mercury (II) in aqueous solutions and live cells with a chemosensor based on tyrosine, Spectrochim. Acta, Part A, 2020, 230, 118004.
85. J. C. Qin, J. Yan, B. D. Wang and Z. Y. Yang, Rhodamine–naphthalene conjugate as a novel ratiometric fluorescent probe for recognition of Al³⁺, Tetrahedron Lett., 2016, 57, 1935–1939.
86. K. Wechakorn, K. Suksen, P. Piyachaturawat and P. Kongsaeree, Rhodamine-based fluorescent and colorimetric sensor for zinc and its application in bioimaging, Sens. Actuators, B, 2016, 228, 270–277.
87. M. Devi, A. Dhir and C. P. Pradeep, A sandwich-type zinc complex from a rhodamine dye based ligand: a potential fluorescent chemosensor for acetate in human blood plasma and a molecular logic gate with INHIBIT function, New J. Chem., 2016, 40, 1269–1277.
88. Y. Wang, H. Q. Chang, W. N. Wu, X. L. Zhao, Y. Yang, Z. Q. Xu, Z. H. Xu and L. Jia, Rhodamine-2-thioxoquinazolin-4-one conjugate: a highly sensitiveandselective chemosensor for Fe3 + ions and crystal structures of its Ag(I) and Hg(II) complexes, Sens. Actuators, B, 2017, 239, 60–68.
89. Y. L. Lin, R. Sung and K. Sung, Bis(rhodamine)-based polyether type of turn-on fluorescent sensors: selectively sensing Fe(III), Tetrahedron, 2016, 72, 5744–5748.
90. J. Kuchlyan, S. Basak, D. Dutta, A. K. Das, D. Mal and N. Sarkar, A new rhodamine derived fluorescent sensor: Detection of Hg²⁺ at cellular level, Chem. Phys. Lett., 2017, 673, 84–88.
91. S. Hazra, C. Bodhak, S. Chowdhury, D. Sanyal, S. Mandal, K. Chattopadhyay and A. Pramanik, A novel tryptamine-appended rhodamine-based chemosensor for selective detection of Hg²⁺ present in aqueous medium and its biological applications, Anal. Bioanal. Chem., 2019, 411, 1143–1157.
92. Y. Wang, H. Ding, Z. Zhu, C. Fan, Y. Tu, G. Liu and S. Pu, Selective rhodamine–based probe for detecting Hg²⁺ and its application as test strips and cell staining, J. Photochem. Photobiol., A, 2020, 390, 112302.
93. Y. Fang, X. Li, J.-Y. Li, G.-Y. Wang, Y. Zhou, N.-Z. Xu, Y. Hu and C. Yao, Sens. Actuators, B, 2018, 255, 1182–1190.
94. G. Singh, S. I. Reja, V. Bhalla, D. Kaur, P. Kaur, S. Arora and M. Kumar, Hexaphenylbenzene appended AIEE active FRET based fluorescent probe for selective imaging of Hg²⁺ ions in MCF-7 cell lines, Sens. Actuators, B, 2017, 249, 311–320.
95. M. She, S. Wu, Z. Wang, S. Ma, Z. Yang, B. Yin, P. Liu, S. Zhang and J. Li, Exploration of congeneric Hg (II)-mediated chemosensors driven by S-Hg affinity, and their application in living system, Sens. Actuators, B, 2017, 247, 129–138.
96. P. Venkatesan, N. Thirumalivasan and S. P. Wu, A Rhodamine-based chemosensor with diphenylselenium for highly selective fluorescence turn-on detection of Hg²⁺in vitro and in vivo, RSC Adv., 2017, 7, 21733–21739.
97. G. Yang, X. Meng, S. Fang, H. Duan, L. Wang and Z. Wang, A highly selective colorimetric fluorescent probe for detection of Hg²⁺ and its application on test strips, RSC Adv., 2019, 9, 8529–8536.
98. M. Hong, Y. Chen, Y. Zhang and D. Xu, A novel rhodamine-based Hg²⁺ sensor with a simple structure and fine performance, Analyst, 2019, 144, 7351–7358.
99. M. Ozdemir, A rhodamine-based colorimetric and fluorescent probe for dual sensing of Cu²⁺ and Hg²⁺ ions, J. Photochem. Photobiol., A, 2016, 318, 7–13.
100. S. Erdemir, M. Yuksekogul, S. Karakurt and O. Kocyigit, Dual-channel fluorescent probe based on bisphenol A-rhodamine for Zn²⁺ and Hg²⁺ through different signaling mechanisms and its bioimaging studies, Sens. Actuators, B, 2017, 241, 230–238.
101. D. Cheng, W. Zhao, H. Yang, Z. Huang, X. Liu and A. Han, Detection of Hg²⁺ by a FRET ratiometric fluorescent probe based on a novel BODIPY-RhB system, Tetrahedron Lett., 2016, 57, 2655–2659.
102. M. Hong, S. Lu, F. Lv and D. Xu, A novel facilely prepared rhodamine-based Hg²⁺ fluorescent probe with three thiourea receptors, Dyes Pigm., 2016, 127, 94–99.
103. C. Kan, X. Shao, F. Song, J. Xu, J. Zhu and L. Du, Bioimaging of a fluorescence rhodamine-based probe for reversible detection of Hg (II) and its application in real water environment, Microchem. J., 2019, 150, 104142.
104. B. Gu, L. Huang, W. Su, X. Duan, H. Li and S. Yao, A benzothiazole-based fluorescent probe for distinguishing and bioimaging of Hg²⁺ and Cu²⁺, Anal. Chim. Acta, 2017, 954, 97.
105. L. Lan, Q. Niu and T. Li, A highly selective colorimetric and ratiometric fluorescent probe for instantaneous sensing of Hg²⁺ in water, soil and seafood and its application on test strips, Anal. Chim. Acta, 2018, 1023, 105.
106. D. Xu, L. Tang, M. Tian, P. He and X. Yan, A benzothizole-based fluorescent probe for Hg²⁺ recognition utilizing ESIPT coupled AIE characteristics, Tetrahedron Lett., 2017, 58, 3654–3657.
107. T. Leng, Y. Ma and G. Chen, A novel ratiometric fluorescence and colorimetric probe with a large Stokes shift for Hg²⁺ sensing, J. Photochem. Photobiol., A, 2018, 353, 143–149.
108. L. Huang, Z. Yang, Z. Zhou, Y. Li, S. Tang, W. Xiao, M. Hu, C. Peng, Y. Chen, B. Gu and H. Li, A dual colorimetric and near-infrared fluorescent turn-on probe for Hg²⁺ detection and its applications, Dyes Pigm., 2019, 163, 118–125.
109. Y. Zhou, X. He, H. Chen, Y. Wang, S. Xiao, N. Zhang, D. Li and K. Zheng, An ESIPT/ICT modulation based ratiometric fluorescent probe for sensitive and selective sensing Hg²⁺, Sens. Actuators, B, 2017, 247, 626–631.
110. (a) Y. Y. Liu, S. Naha, N. Thirumalaivasan, S. Velmathi and S. P. Wu, A novel nanomolar highly selective fluorescent probe for imaging mercury (II) in living cells and zebrafish, Sens. Actuators, B, 2018, 277, 673–678; (b) M. Tian, C. Wang, Q. Ma, Y. Bai, J. Sun and C. Ding, A Highly Selective Fluorescent Probe for Hg²⁺ Based on a 1, 8-Naphthalimide Derivative, ACS Omega, 2020, 5, 18176–18184; (c) Z. Wang, Y. Zhang, J. Yin, Y. Yang, H. Luo, J. Song, X. Xu and S. Wang, A novel camphor-based “turn-on” fluorescent probe with high specificity and sensitivity for sensing mercury (II) in aqueous medium and its bioimaging application, ACS Sustainable Chem. Eng., 2020, 8, 12348–12359.
111. J. Shanmugapriya, S. Singaravadivel, G. Sivaraman and D. Chellappa, Anthracene-based highly selective and sensitive fluorescent “turn-on” chemodosimeter for Hg²⁺, ACS Omega, 2018, 3, 12341–12348.
112. S. L. Pan, K. Li, L. L. Li, M. Y. Li, L. Shi, Y. H. Liu and X. Q. Yu, A reaction-based ratiometric fluorescent sensor for the detection of Hg (ii) ions in both cells and bacteria, Chem. Commun., 2018, 54, 4955–4958.
113. C. Wu, J. Wang, J. Shen, C. Bi and H. Zhou, Coumarin-based Hg²⁺ fluorescent probe: Synthesis and turn-on fluorescence detection in neat aqueous solution, Sens. Actuators, B, 2017, 243, 678–683.
114. M. Dong, J. Tang, Y. Lv, Y. Liu, J. Wang, T. Wang, J. Bian and C. Li, A dual–function fluorescent probe for Hg(II) and Cu(II) ions with two mutually independent sensing pathways and its logic gate behavior, Spectrochim. Acta, Part A, 2020, 226, 117645.
115. Y. Chen, C. Yang, Z. Yu, B. Chen and Y. Han, A highly sensitive hemicyanine-based fluorescent chemodosimeter for mercury ions in aqueous solution and living cells, RSC Adv., 2015, 5, 82531–82534.
116. A. Gomathi and P. Viswanathamurthi, Near-infrared fluorogenic switches for the detection of Hg (II) ions: applications in real samples and living cells, Anal. Methods, 2019, 11, 2769–2777.
117. B. Gu, L. Huang, N. Mi, P. Yin, Y. Zhang, X. Tu, X. Luo, S. Luo and S. Yao, An ESIPT-based fluorescent probe for highly selective and ratiometric detection of mercury(II) in solution and in cells, Analyst, 2015, 140, 2778–2784.
118. C. Zhang, H. Zhang, M. Li, Y. Zhou, G. Zhang, L. Shi, Q. Yao, S. Shuang and C. Dong, A turn-on reactive fluorescent probe for Hg²⁺ in 100% aqueous solution, Talanta, 2019, 197, 218–224.
119. Y. Gao, C. Zhang, S. Peng and H. Chen, A fluorescent and colorimetric probe enables simultaneous differential detection of Hg²⁺ and Cu²⁺ by two different mechanisms, Sens. Actuators, B, 2017, 238, 455–461.
120. Y. Jiao, X. Liu, L. Zhou, H. He, P. Zhou and C. Duan, A Schiff-base dual emission ratiometric fluorescent chemosensor for Hg²⁺ ions and its application in cellular imaging, Sens. Actuators, B, 2017, 247, 950–956.
121. Y. Li, S. Qi, C. Xia, Y. Xu, G. Duan and Y. Ge, A FRET ratiometric fluorescent probe for detection of Hg²⁺ based on an imidazo [1, 2-a] pyridine-rhodamine system, Anal. Chim. Acta, 2019, 1077, 243–248.
122. Y. Ge, A. Liu, R. Ji, S. Shen and X. Cao, Detection of Hg²⁺ by a FRET ratiometric fluorescent probe based on a novel pyrido [1,2-a] benzimidazole-rhodamine system, Sens. Actuators, B, 2017, 251, 410–415.
123. A. Tantipanjaporn, S. Prabpai, K. Suksen and P. Kongsaeree, A thiourea-appended rhodamine chemodosimeter for mercury(II) and its bioimaging application, Spectrochim. Acta, Part A, 2018, 192, 101–107.
124. (a) C. G. Chen, N. Vijay, N. Thirumalaivasan, S. Velmathi and S. P. Wu, Coumarin-based Hg²⁺ fluorescent probe: Fluorescence turn-on detection for Hg²⁺ bioimaging in living cells and zebrafish, Spectrochim. Acta, Part A, 2019, 219, 135–140; (b) G. Singh, P. Raj, H. Singh and N. Singh, Colorimetric detection and ratiometric quantification of mercury(II) using azophenol dye:‘dip & read’based handheld prototype device development, J. Mater. Chem. C, 2018, 6, 12728–12738.
125. A. Malek, K. Bera, S. Biswas, G. Perumal, A. K. Das, M. Doble, T. Thomas and E. Prasad, Development of a next-generation fluorescent turn-on sensor to simultaneously detect and detoxify mercury in living samples, Anal. Chem., 2019, 91, 3533–3538.
126. A. Picard-Lafond, D. Lariviere and D. Boudreau, Revealing the hydrolysis mechanism of a Hg²⁺-reactive fluorescein probe: Novel insights on thionocarbonated Dyes, ACS Omega, 2020, 5, 701–711.
127. J. Xu, Z. Xu, Z. Wang, C. Liu, B. Zhu, X. Wang, K. Wang, J. Wang and G. Sang, A carbonothioate-based highly selective fluorescent probe with a large Stokes shift for detection of Hg²⁺, Luminescence, 2018, 33, 219–224.
128. D. Zhang, J. Liu, H. Yin, H. Wang, S. Li, M. Wang, M. Li, L. Zhou and J. Zhang, A Turn on ESIPT Probe for Rapid and Ratiometric Fluorogenic Detection of Hg²⁺ and its Application in Live-Cell Imaging, J. Fluoresc., 2016, 26, 1367–1372.
129. X. Duan, Z. Li, F. He and S. Wang, A sensitive and homogeneous SNP detection using cationic conjugated polymers, J. Am. Chem. Soc., 2007, 129, 4154–4155.
130. B. Liu and G. C. Bazan, Homogeneous fluorescence-based DNA detection with water-soluble conjugated polymers, Chem. Mater., 2004, 16, 4467–4476.
131. X. Cheng, Q. Li, J. Qin and Z. Li, A new approach to design ratiometric fluorescent probe for mercury (II) based on the Hg²⁺-promoted deprotection of thioacetals, ACS Appl. Mater. Interfaces, 2010, 2, 1066–1072.
132. S. Sarkar and R. Shunmugam, Polynorbornene derived 8-hydroxyquinoline paper strips for ultrasensitive chemical nerve agent surrogate sensing, Chem. Commun., 2014, 50, 8511–8513.
133. S. Sarkar, A. Mondal, A. K. Tiwari and R. Shunmugam, Unique emission from norbornene derived terpyridine-a selective chemodosimeter for G-type nerve agent surrogates, Chem. Commun., 2012, 48, 4223–4225.
134. S. Bhattacharya and R. Shunmugam, Unique norbornene based triazole molecule for selective Fe (II) sensing, RSC Adv., 2015, 5, 74973–74976.
135. J. Ding, H. Li, Y. Xie, Q. Peng, Q. Li and Z. Li, Reaction-based conjugated polymer fluorescent probe for mercury(II): good sensing performance with “turn-on” signal output, Polym. Chem., 2017, 8, 2221–2226.
136. U. Haldar and H. I. Lee, BODIPY-derived multi-channel polymeric chemosensor with pH-tunable sensitivity: selective colorimetric and fluorimetric detection of Hg²⁺ and HSO₄⁻ in aqueous media, Polym. Chem., 2018, 9, 4882–4890.
137. H. J. Kim and H. I. Lee, Thermo-tunable colorimetric detection of mercury (II) ions driven by the temperature-dependent assembly and disassembly of a block copolymer, Polym. Chem., 2019, 10, 4017–4024.
138. A. Balamurugan and H. I. Lee, Water-soluble polymeric probes for the selective sensing of mercury ion: pH-driven controllable detection sensitivity and time, Macromolecules, 2015, 48, 1048–1054.
139. B. Wu, L. Xu, S. Wang, Y. Wang and W. Zhang, A PEGylated colorimetric and turn-on fluorescent sensor based on BODIPY for Hg (II) detection in water, Polym. Chem., 2015, 6, 4279–4289.
140. N. Choudhury, B. Saha, B. Ruidas and P. De, Dual-action polymeric probe: turn-on sensing and removal of Hg²⁺; chemosensor for HSO₄⁻, ACS Appl. Polym. Mater., 2019, 1, 461–471.
141. N. Choudhury, B. Ruidas, B. Saha, K. Srikanth, C. D. Mukhopadhyay and P. De, Multifunctional tryptophan-based fluorescent polymeric probes for sensing, bioimaging and removal of Cu²⁺ and Hg²⁺ ions, Polym. Chem., 2020, 11, 2015–2026.
142. (a) U. Haldar and H. I. Lee, BODIPY-derived polymeric chemosensor appended with thiosemicarbazone units for the simultaneous detection and separation of Hg (II) ions in pure aqueous media, ACS Appl. Mater. Interfaces, 2019, 11, 13685–13693; (b) K. Chauhan, P. Singh and R. K. Singhal, New chitosan–thiomer: an efficient colorimetric sensor and effective sorbent for mercury at ultralow concentration, ACS Appl. Mater. Interfaces, 2015, 7, 26069–26078.
143. S. Sirawatcharin, A. Saithongdee, A. Chaicham, B. Tomapatanaget, A. Imyim and N. Praphairaksit, Naked-eye and colorimetric detection of arsenic (III) using difluoroboron-curcumin in aqueous and resin bead support systems, Anal. Sci., 2014, 30, 1129–1134.
144. T. G. Akshay Krishna, V. Tekuri, M. Mohan and D. R. Trivedi, Selective colorimetric chemosensor for the detection of Hg²⁺ and arsenite ions using Isatin based Schiff's bases; DFT Studies and Applications in test strips, Sens. Actuators, B, 2019, 284, 271–280.
145. S. Lohar, S. Pal, B. Sen, M. Mukherjee, S. Banerjee and P. Chattopadhyay, Selective and sensitive turn-on chemosensor for arsenite ion at the ppb level in aqueous media applicable in cell staining, Anal. Chem., 2014, 86, 11357–11361.
146. S. Paul, S. Bhuyan, S. K. Mukhopadhyay, N. C. Murmu and P. Banerjee, Sensitive and selective in vitro recognition of biologically toxic As (III) by rhodamine based chemoreceptor, ACS Sustainable Chem. Eng., 2019, 7, 13687–13697.
147. M. Baglan and S. Atılgan, Selective and sensitive turn-on fluorescent sensing of arsenite based on cysteine fused tetraphenylethene with AIE characteristics in aqueous media, Chem. Commun., 2013, 49, 5325–5327.
148. A. S. M. Islam, R. Alam, A. Katarkar, K. Chaudhuri and M. Ali, Di-oxime based selective fluorescent probe for arsenate and arsenite ions in a purely aqueous medium with living cell imaging applications and H-bonding induced microstructure formation, Analyst, 2015, 140, 2979–2983.
149. K. Chauhan, P. Singh, B. Kumari and R. K. Singhal, Synthesis of new benzothiazole Schiff base as selective and sensitive colorimetric sensor for arsenic on-site detection at ppb level, Anal. Methods, 2017, 9, 1779–1785.
150. M. L. Presti, S. El Sayed, R. Martínez-Máñez, A. M. Costero, S. Gil, M. Parra and F. Sancenon, Selective chromo-fluorogenic detection of trivalent cations in aqueous environments using a dehydration reaction, New J. Chem., 2016, 40, 9042–9045.
151. N. Yadav and A. K. Singh, Dual anion colorimetric and fluorometric sensing of arsenite and cyanide ions, RSC Adv., 2016, 6, 100136–100144.
152. R. Purkait, S. Maity and C. Sinha, A hydrazine-based thiocarbamide probe for colorimetric and turn-on fluorometric detection of PO₄³⁻ and AsO₃³⁻ in semi-aqueous medium, New J. Chem., 2018, 42, 6236–6246.
153. P. G. Sutariya, H. Soni, S. A. Gandhi and A. Pandya, Single-step fluorescence recognition of As³⁺, Nd³⁺ and Br⁻ using pyrene-linked calix [4] arene: application to real samples, computational modelling and paper-based device, New J. Chem., 2019, 43, 737–747.
154. A. Deepa and V. Padmini, Highly Efficient Colorimetric Sensor for Selective and Sensitive Detection of Arsenite Ion (III) in Aqueous Medium, J. Fluoresc., 2019, 29, 813–818.
155. V. C. Ezeh and T. C. Harrop, A sensitive and selective fluorescence sensor for the detection of arsenic (III) in organic media, Inorg. Chem., 2012, 51, 1213–1215.
156. V. C. Ezeh and T. C. Harrop, Synthesis and properties of arsenic (III)-reactive coumarin-appended benzothiazolines: a new approach for Inorganic arsenic detection, Inorg. Chem., 2013, 52, 2323–2334.
157. S. Bhattacharya, S. Sarkar and R. Shunmugam, Unique norbornene polymer based “in-field” sensor for As (III), J. Mater. Chem. A, 2013, 1, 8398–8405.

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