Mechanistic Innovations in Fluorescent Chemosensors for Detecting Toxic Ions: PET, ICT, ESIPT, FRET and AIE Approaches

Abstract

Fluorescent chemosensors have become vital tools for detecting toxic ions due to their exceptional sensitivity, selectivity, and rapid response times. These sensors function through various mechanisms, each providing unique advantages for specific applications. This review offers a comprehensive overview of the mechanistic innovations in fluorescent chemosensors, emphasizing five key approaches: Photoinduced Electron Transfer (PET), Fluorescence Resonance Energy Transfer (FRET), Intramolecular Charge Transfer (ICT), Aggregation-Induced Emission (AIE), and Excited-State Intramolecular Proton Transfer (ESIPT). We highlight the substantial progress made in developing these chemosensors, discussing their design principles, sensing mechanisms, and practical applications, with a particular focus on their use in detecting toxic ions relevant to environmental and biological contexts.

Introduction

The detection of toxic ions is a critical task in environmental monitoring, industrial processes, and biomedical diagnostics. Toxic ions, such as heavy metals and harmful anions, pose significant threats to human health and ecosystems [1,2,3]. Traditional methods for detecting these ions, such as atomic absorption spectroscopy and inductively coupled plasma mass spectrometry, although highly sensitive and specific, are often limited by their complexity, high cost, and the need for extensive sample preparation. Consequently, there is a growing demand for more practical, efficient, and cost-effective detection methods. Fluorescent chemosensors have emerged as promising alternatives due to their high sensitivity, selectivity, rapid response times, and ease of use. These sensors operate by converting the presence of a target ion into a measurable fluorescence signal, enabling real-time and in-situ analysis. The versatility of fluorescent chemosensors is largely attributed to the diverse mechanisms by which they can interact with target ions, each offering distinct advantages tailored to specific detection requirements [4, 5].

This review delves into the mechanistic innovations underpinning the development of fluorescent chemosensors, focusing on five major approaches: Photoinduced Electron Transfer (PET), Fluorescence Resonance Energy Transfer (FRET), Intramolecular Charge Transfer (ICT), Aggregation-Induced Emission (AIE), and Excited-State Intramolecular Proton Transfer (ESIPT). Understanding these mechanisms is crucial for designing effective chemosensors, as each mechanism influences the sensor's performance characteristics, including sensitivity, selectivity, and operational conditions. In this review, we aim to provide a thorough analysis of these five mechanistic approaches, highlighting the design principles, operational mechanisms, and practical applications of fluorescent chemosensors (Table 1). We explore the recent advancements and innovations in detecting toxic ions that are important for the environment and biology, and we discuss future directions and potential challenges in this field [6,7,8,9,10].

Table 1 Summary of mechanism based analytes detection using colorimetric and fluorescent chemosensor method

Phenomena of fluorescence

Fluorescence is a photophysical phenomenon where a substance absorbs photons, usually in the ultraviolet or visible spectrum, and subsequently re-emits photons at a longer wavelength. This process involves several key steps such as excitation, vibrational relaxation, internal conversion and fluorescence emission. Fluorescence lifetimes, typically ranging from nanoseconds to microseconds, and quantum yields, which measure the efficiency of fluorescence, are crucial parameters. Fluorescence spectroscopy and microscopy exploit these properties for diverse applications, including biological imaging, where fluorophores tag specific biomolecules, and materials science, where fluorescence signals indicate specific structural or compositional information. Environmental factors such as solvent polarity, temperature, and pH can significantly influence fluorescence intensity and spectra [11, 12], making fluorescence a sensitive probe for studying molecular environments and dynamics (Fig. 1).

Fig. 1

Jablonski Diagram for Fluorescence and phosphorescence

Fluorophores

Fluorophores, also known as fluorescent dyes, are molecules that can re-emit light upon light excitation. They are pivotal in various scientific and medical fields due to their ability to emit fluorescence. When a fluorophore absorbs a photon, its electrons are excited from the ground state to a higher energy state. The electrons then return to the ground state, releasing energy in the form of visible light, a process known as fluorescence. The emitted light is of a longer wavelength (lower energy) compared to the absorbed light, a phenomenon referred to as the Stokes shift. Fluorophores typically consist of conjugated systems with alternating double and single bonds, enabling delocalization of π-electrons. This structure allows them to absorb and emit light efficiently. The properties of fluorophores, such as their excitation and emission wavelengths, quantum yield, and fluorescence lifetime, are highly dependent on their chemical structure. Modifications in the molecular structure can tailor these properties for specific applications [13,14,15]. Fluorophores are categorized based on their chemical nature and application (Fig. 2).

• a) Organic Dyes: These include fluorescein, rhodamine, and cyanine dyes. They are widely used due to their strong fluorescence and diverse spectral properties.

• b) Inorganic Fluorophores: Such as quantum dots and rare earth chelates, offer high brightness and photostability, making them suitable for long-term imaging.

• c) Genetically Encoded Fluorophores: Green Fluorescent Protein (GFP) and its derivatives are used extensively in biological research for live cell imaging.

Fig. 2

Types of Fluorophores

Fluorophores are indispensable tools in modern science and technology. Their unique ability to emit light upon excitation allows detailed investigation of environmental pollution detection, biological systems, materials, and chemical environments. Continuous advancements in fluorophore design and application promise to further enhance their utility and impact across various scientific disciplines [16, 17].

Solvent and environmental effects

Fluorophores are highly sensitive to their environment. Factors such as solvent polarity, pH, temperature, and the presence of quenching agents can significantly affect their fluorescence properties. This sensitivity makes them powerful tools for probing the microenvironment in complex systems [18,19,20].

Solvent Effects

Changes in solvent polarity can shift excitation and emission spectra. Solvent effects on the excitation and emission spectra of molecules, particularly fluorescent molecules, are a crucial aspect of photophysics and photochemistry. Changes in solvent polarity can cause significant shifts in these spectra due to interactions between the solvent molecules and the electronic states of the solute (the fluorescent molecule).

pH Sensitivity

Certain fluorophores, like fluorescein, have fluorescence properties that vary with pH, useful for measuring pH changes in biological systems.

Temperature

Higher temperatures can lead to increased non-radiative decay rates, reducing fluorescence intensity.

Mechanism based fluorescence chemosensors

Photoinduced Electron Transfer mechanism (PET)

Photoinduced Electron Transfer (PET) is widely used in the design of fluorescent sensors for detecting protons and metal ions. PET involves the movement of an electron, initiated by light absorption, from an electron-rich donor to an electron-deficient acceptor. When light is absorbed, an electron is promoted from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO), creating an excited state. The energy required to remove an electron from the highest molecular orbital to the vacuum is called the ionization potential (IP). The excited state has a lower ionization potential than the ground state.

In the excited state, the donor molecule’s LUMO is populated, allowing an exothermic electron transfer to the acceptor’s LUMO, forming a radical ion pair. Alternatively, if the acceptor molecule is photoexcited, its LUMO is populated, creating a vacancy in the acceptor’s HOMO. An exothermic electron transfer from the donor’s HOMO to this vacancy then occurs, also generating a radical ion pair. The system can return to its original state by a back electron transfer from the acceptor’s LUMO to the donor’s HOMO vacancy created during PET (Fig. 3).

Fig. 3

Photoinduced Electron Transfer mechanism

A novel receptor, R1, derived from 8-hydroxyquinoline-5-carbaldehyde Schiff-base, has been developed for the selective and sensitive detection of Al³⁺ ions in a 10% (v/v) methanol–water mixture (acetate buffer, pH 4.5), outperforming other metal ions [21]. In its free state, receptor R1 exhibits weak fluorescence at 480 nm when excited at 378 nm. This weak emission is attributed to the photoinduced electron-transfer (PET) effect, where the lone pair electrons from the Schiff-base and quinoline nitrogen atoms quench the fluorescence. Upon the introduction of Al³⁺ ions, there is a significant enhancement in fluorescence, increasing by 30-fold. This dramatic increase in fluorescence is due to the highly efficient chelation-enhanced fluorescence (CHEF) effect when Al³⁺ binds to R1. Other metal cations do not produce a similar enhancement in fluorescence. Fluorescence studies revealed that the stoichiometry of the R1-Al³⁺ complex follows a 1:2 binding mode. The detection limit for Al³⁺ was determined to be below 10^–7 M (Fig. 4).

Fig. 4

Sensing mechanism of R1 with Al³⁺ ions

A novel quinoline-Schiff base fluorescent receptor, R2, specifically 2-(2-hydroxybenzylidene)hydrazonomethyl)quinolin-8-ol, has been synthesized and thoroughly characterized [22]. Receptor R2 demonstrates exceptional selectivity and sensitivity towards Cu²⁺ ions in a DMSO/H₂O solution (1:1 v/v, 0.01 M Tris–HCl buffer, pH 7.20). Due to intermolecular π–π* charge transfer (CT) transitions, R2 displays two prominent absorption peaks at 299 nm and 352 nm. When Cu²⁺ ions are added, the initially colorless R2 solution turns yellowish-green. In its fluorescence spectrum, R2 exhibits weak fluorescence (Φ = 0.049) at 623 nm upon excitation at 352 nm, attributed to the excited-state intramolecular proton transfer (ESIPT) mechanism. This weak fluorescence arises from the photoinduced electron-transfer (PET) process from the nitrogen atom near the phenol group to the naphthyl fluorophore, as well as cis–trans isomerization around the C = N bond in R2. Introducing Cu²⁺ ions to R2 significantly enhances fluorescence. The absorption at 352 nm corresponds to the enol form of the probe, while the keto tautomers, resulting from ESIPT from the phenolic hydroxyl to the nitrogen atoms of the Schiff base, are responsible for the stronger emission at 623 nm. The binding constant (K) and stoichiometry of R2 with Cu²⁺ ions were determined to be 3.38 × 10^–4 M⁻¹ at 299 nm and 3.63 × 10^–4 M⁻¹ at 352 nm, with a 1:1 binding mode and a detection limit of 8.08 nM (Fig. 5).

Fig. 5

Structure of R2

A novel fluorescent receptor, R3, identified as 4(1H-benzo[d]imidazol-2-yl)-2-(pyridin-2-yl)quinoline, has been developed for the selective detection of copper ions (Cu²⁺) in CH₃CN-HEPES buffer solution (pH 7, 10 mM, 9:1 v/v) [23]. The sensing capabilities of R3 were evaluated against various metal ions, including Na⁺, Mg²⁺, K⁺, Mn²⁺, Ca²⁺, Fe²⁺, Co²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Ba²⁺, Hg²⁺, and Pb²⁺. Upon the addition of Cu²⁺ to R3, the fluorescence intensity significantly decreased from Φ = 0.239 to Φ = 0.0012. Additionally, the absorption band of R3 at 332 nm diminished and exhibited a slight red shift to 345 nm. As the concentration of Cu²⁺ increased, the absorption band at 345 nm gradually intensified, indicating a typical photoinduced electron transfer (PET) process. In the emission spectrum the free receptor showing an intensity band at 440 nm and the band was declined upon the incremental addition of Cu²⁺ ions. The binding constant, binding stoichiometry and detection limit of R3 with Cu²⁺ were determined to be 3.38 × 10^–5 M⁻¹, 1:1, and 1.86 µM, respectively (Fig. 6).

Fig. 6

Structure of R3

A novel quinoline-based receptor, R4, has been designed and synthesized for the detection of mercury ions (Hg²⁺). Metal ion recognition studies were conducted using CHCl₃/CH₃OH (1:1 v/v) and aqueous organic solvents [24]. Initially, the quinoline moiety exhibited an absorption band at 300 nm, which decreased while a new red-shifted absorption band at 355 nm emerged with increasing Hg²⁺ ion concentration. An isosbestic point was clearly observed at 330 nm. Gradual addition of Hg²⁺ ions to R4 resulted in a significant decrease in emission intensity at 395 nm, accompanied by the appearance of a new emission peak centered at 482 nm. This shift is attributed to the formation of an excimer between the quinoline moieties, which are brought closer together due to strong Hg²⁺ chelation within the R4 cavity. The association constant and stoichiometry for the Hg²⁺ complex were determined to be 2.15 × 10^–4 M⁻¹ and 1:1, respectively. Additionally, the presence of Zn²⁺ and Cd²⁺ ions enhanced the fluorescence spectrum, which is due to the inhibition of the photoinduced electron transfer (PET) process between the excited state of quinoline and the binding site (Fig. 7).

Fig. 7

Structure of R4

A novel fluorescent receptor, R5, based on a quinoline moiety, has been developed and examined for its sensing capabilities towards Zn²⁺ and Cd²⁺ in an aqueous solution (25 mM HEPES, 0.1 M NaNO₃, pH 7.4) [25]. In water, free receptor R5 exhibits weak fluorescence (Φ = 0.023). Upon the addition of Zn²⁺, a significant fluorescence enhancement is observed at 373 nm and 509 nm. The enhancement at 509 nm is attributed to the binding of Zn²⁺ to the imidic acid tautomer of R5, which results in an expanded conjugated system. This binding blocks the intra-molecular photoinduced electron transfer (PET) process, leading to increased fluorescence. When Cd²⁺ is added to R5, turn-on fluorescence is observed at 373 nm. The amide tautomer of R5 binds with Cd²⁺, also blocking the intra-molecular PET process and causing an increase in fluorescence intensity at 373 nm. The dissociation constants for the Zn²⁺ and Cd²⁺ complexes were found to be 3.36 nM and 30.62 nM, respectively. The stoichiometry for the binding of receptor R5 with both Zn²⁺ and Cd²⁺ was determined to be 1:1 (Fig. 8).

Fig. 8

Structure of R5 and its fluorescence behaviour towards Cd²⁺

A novel quinoline-coupled pyrazole receptor, R6, has been developed as a colorimetric and fluorescent sensor for the selective detection of Zn²⁺ in an EtOH-H₂O solution (1:1 v/v, 50 mM HEPES, pH 7.2) [26]. Upon the addition of Zn²⁺ to R6, the absorption bands at 280 nm and 323 nm gradually decrease, and a new absorption band appears at 380 nm, accompanied by a noticeable color change from colorless to pale yellow. Other metal ions such as Na⁺, K⁺, Cu²⁺, Cd²⁺, Ni²⁺, Hg²⁺, Pb²⁺, Co²⁺, Ca²⁺, Mn²⁺, Cr³⁺, Ba²⁺, Mg²⁺, Fe²⁺, Fe³⁺, Al³⁺, Zr²⁺, Ce³⁺, and Ag⁺ do not induce any visual, absorption, or emission changes in R6. The free receptor R6 exhibits weak fluorescence (Φ = 0.019) with emission at 408 nm. Upon interaction with Zn²⁺, the fluorescence shifts slightly from 408 to 418 nm and is significantly enhanced (Φ = 0.214). These spectral changes are due to the inhibition of the photoinduced electron transfer (PET) process and the restricted C = N isomerization mechanism. The binding constant, stoichiometry, and detection limit of R6 with Zn²⁺ are calculated to be 1.88 × 10^–4 M⁻¹, 1:1, and 2.9 nM, respectively. The receptor R6 has also been successfully utilized for selective imaging of Zn²⁺ in living cells (Fig. 9). Cadmium (Cd²⁺) typically forms complexes with larger coordination numbers (up to 8) and prefers softer ligands like sulfur. In contrast, Zn²⁺ usually forms complexes with lower coordination numbers (4 to 6) and favors harder ligands like oxygen and nitrogen. The distinct preferences in ligand types and coordination environments allow for the differentiation between Cd²⁺ and Zn²⁺ binding.

Fig. 9

Structure of R6 and its fluorescence bioimaging

A quinoline-Schiff base fluorescent receptor, R7, has been reported for the selective and sensitive detection of Zn²⁺ in ethanol, even in the presence of various interfering metal ions [27]. When receptor R7 is excited at 375 nm, it exhibits weak fluorescence due to the photoinduced electron transfer (PET) phenomenon from the lone pair electrons of the Schiff-base nitrogen atom to the benzene moiety of R7. However, upon the addition of Zn²⁺, a significant fluorescence enhancement at 450 nm is observed. This enhancement occurs because the complexation of R7 with Zn²⁺ inhibits the PET phenomenon. Among the various interfering metal ions tested, only Cr³⁺ and Hg²⁺ caused fluorescence quenching due to the photoinduced electron and energy transfer processes. The detection limit, stoichiometry, and binding constant of receptor R7 with Zn²⁺ were determined to be 3.5 µM, 1:1, and 2.3 × 10^–4 M⁻¹, respectively (Fig. 10).

Fig. 10

Structure of R7 and its sensing mechanism towards Co²⁺ and Zn²⁺

A quinoline-based turn-on chemosensor, receptor R8, demonstrates high selectivity and sensitivity for Zn²⁺ in a MeOH-Tris buffer (7/3 v/v, pH 7.3) compared to other interfering metal ions [28]. Due to the photoinduced electron transfer (PET) process involving the non-bonding electron pairs of nitrogen atoms in the picolinohydrazide moiety, receptor R8 exhibits weak fluorescence. However, upon the addition of various metal ions, a significant fluorescence enhancement is observed around 490 nm specifically when Zn²⁺ binds to R8. This binding also results in a noticeable color change from colorless to light green. The fluorescence enhancement due to Zn²⁺ is attributed to the inhibition of the PET effect from the electron-donating picolinohydrazide moiety to the electron-accepting 8-aminoquinoline moiety. Additionally, the R8-Zn²⁺ complex can serve as a new cascade chemosensor for sequential detection of pyrophosphate (PPi) and sulfide (S²⁻), leading to a fluorescence "OFF–ON–OFF" switching pattern. The binding constant and stoichiometry of receptor R8 with Zn²⁺ are determined to be 6.7 × 10⁵ M⁻¹ and 1:1, respectively. The detection limits of R8 are calculated to be 3.8 × 10^–8 M for Zn²⁺, 3.7 × 10^–7 M for PPi, and 4.9 × 10^–7 M for S²⁻ (Fig. 11).

Fig. 11

Structure of R8

A novel 7-hydroxyquinoline-based fluorescent receptor, R9, has been developed for the selective detection of Zn²⁺ in HEPES buffer (25 mM HEPES, 0.1 M NaClO₄, 5% (v/v) DMSO, pH 7.4) [29]. Receptor R9 features a methoxy group at the 7-position of the quinoline ring. When excited at 320 nm, R9 exhibits weak fluorescence emission at 393 nm. However, upon the addition of Zn²⁺, the fluorescence emission intensity increases significantly (Φ = 0.556). This enhanced fluorescence is due to the inhibition of the photoinduced electron transfer (PET) mechanism. The binding mode of R9 with Zn²⁺ was determined to be 1:1, and the dissociation constant was found to be 0.117 nM. R9 also demonstrates higher selectivity for Zn²⁺ over Cd²⁺. Additionally, a cell-permeable derivative of R9 can be utilized for imaging Zn²⁺ in living cells using two-photon microscopy (Fig. 12).

Fig. 12

Structure of R9 and Zn.²⁺ in living cells (imaging)

Two fluorescein-quinoline based derivatives, R10a (2-[2-chloro-6-hydroxy-3-oxo-5-(quinolin-8-ylaminomethyl)-3H-xanthen-9-yl]benzoic acid) and R10b (2-[6-hydroxy-3-oxo-4,5-bis-(quinolin-8-ylaminomethyl)-3H-xanthen-9-yl]benzoic acid), were designed, synthesized, and characterized [30]. Both dyes exhibit excellent selectivity for Zn²⁺ in a buffer solution containing 50 mM PIPES and 100 mM KCl at pH 7. Free receptors R10a and R10b show weak fluorescence (R10a: Φ = 0.024; R10b: Φ = 0.50). Upon binding with Zn²⁺, a 33-fold fluorescence enhancement at 524 nm is observed, with quantum yields of 0.78 for R10a and 0.71 for R10b. In the absorption spectrum, a blue shift from 505 to 498 nm occurs upon Zn²⁺ binding with R10a and R10b. These changes indicate a perturbation of the fluorescein π system, likely due to Zn²⁺ coordination to the phenol group. Single-photon and multiphoton microscopy confirm that both R10a and R10b are cell-permeable and responsive to Zn²⁺ in vivo (Fig. 13).

Fig. 13

Structure of R10a-b

A fluorescent receptor, R11, conjugated with quinoline and benzimidazole, has been synthesized for the highly selective detection of Zn²⁺ in a HEPES-buffered CH₃CN/H₂O solution (1:1 v/v, pH 7.0), effectively discriminating against interference from other metal ions [31]. Receptor R11 exhibits two absorption bands at 213 nm and 372 nm. Upon addition of Zn²⁺, there is an enhancement in absorption at both 213 nm and 372 nm, accompanied by a noticeable color change from pale yellow to intense yellow. Initially, the emission spectrum of receptor R11 shows weak fluorescence emission at 425 nm, which is attributed to the intramolecular photoinduced electron transfer (PET) process and the unrestricted torsional rotation between the C–C single bond that covalently links the quinoline and benzimidazole units. However, upon addition of Zn²⁺, a prominent enhancement in emission is observed, resulting in intense yellowish-green fluorescence with emission maxima at 425 nm. This fluorescence enhancement is attributed to the inhibition of the PET process between the quinoline-benzimidazole conjugate and the restriction of rotation around the C–C single bond linking the quinoline and benzimidazole rings. The association constant, stoichiometry, and detection limit are calculated to be 1.53 × 10⁴ M⁻¹, 1:1, and 0.15 µM, respectively (Fig. 14).

Fig. 14

Structure of R11 and its sensing mechanism towards Zn²⁺

A water-soluble fluorescent chemosensor, receptor R12, based on a quinoline derivative, was synthesized for the selective detection of zinc ions in a 100% aqueous buffer solution [32]. Upon excitation at 350 nm, receptor R12 exhibits weak fluorescence with a low quantum yield (Φ = 0.00084). This weak fluorescence is attributed to the photo-induced electron transfer (PET) process involving the nonbonding electron pair of tertiary nitrogen, which can transfer an electron to the excited fluorophore, thus quenching the fluorescence. However, upon addition of Zn²⁺, a significant fluorescence enhancement at 500 nm is observed, possibly due to the inhibition of the PET process. The binding constant, detection limit, and binding mode are determined to be K = 1.4 × 10⁴ M⁻¹, 4.48 µM, and 1:1, respectively (Fig. 15).

Fig. 15

Structure of R12 and its complex structure with Zn²⁺

A simple receptor, R13, based on quinoline, specifically 3-((2-(dimethylamino)ethyl)amino)-N-(quinolin-8-yl)propanamide, has been synthesized for detecting Zn²⁺ in a mixture of MeCN and bis–tris buffer solution (3:7 v/v) [33]. The UV–vis absorption spectrum of R13 exhibits two absorption bands at 240 nm and 310 nm. Upon the addition of Zn²⁺ to R13, these absorption bands red-shift to 257 nm and 367 nm, respectively. Additionally, three distinct isosbestic points are observed at 246 nm, 283 nm, and 336 nm, indicating the clear conversion of free receptor R13 to a zinc complex. Exciting free receptor R13 at 370 nm results in weak fluorescence emission at 523 nm. However, upon the addition of Zn²⁺, a significant fluorescence enhancement is observed around 525 nm. The detection limit and stoichiometry of R13 for Zn²⁺ are calculated to be 76 µM and 1:1, respectively (Fig. 16).

Fig. 16

Structure of R13

Intramolecular charge transfer (ICT)

Intramolecular Charge Transfer (ICT) offers an alternative approach to designing toxic ions detection based chemosensors. The ICT fluorescent molecular probe consists of a fluorophore, a strong electron donor, and a strong electron acceptor, which together form a robust push–pull electron system. Upon photoexcitation, charge transfer occurs from the electron donor to the electron acceptor. When the identification group of the ICT fluorescence probe interacts with the target, it alters the push–pull electron effect within the fluorophore. This interaction either weakens or strengthens the intramolecular charge transfer, resulting in changes to the fluorescence spectrum, such as blue shifts or red shifts (Fig. 17).

Fig. 17

Intramolecular Charge Transfer mechanism

Receptor R14, a quinoline-based fluorescence sensor appended with bisphenol A, serves as a multi-analyte detector in an ethanol–water mixture (v/v = 9/1) [34]. Upon the addition of various metal ions to R14, only Zn²⁺ and Al³⁺ induce yellow and green fluorescence emissions, respectively. Initially, R14 exhibits weak fluorescence emission at 550 nm, attributed to the turn-off behavior of the receptor caused by isomerization of the C = N double bond and the intramolecular charge transfer (ICT) effect. However, interaction with Zn²⁺ and Al³⁺ may inhibit the C = N isomerization and ICT effect in R14, leading to a chelation-enhanced fluorescence effect. Consequently, upon addition of Zn²⁺ and Al³⁺ to R14, strong fluorescence enhancements are observed at 560 nm (Φ = 0.172) and 530 nm (Φ = 0.239), respectively. The binding constants, detection limits, and stoichiometries are determined to be 2.32 ± 0.21 × 10¹⁰ M⁻² (Zn²⁺), 0.73 ± 0.17 × 10¹⁰ M⁻² (Al³⁺), 3.56 µM (Zn²⁺), 1.14 µM (Al³⁺), and 1:1 binding mode (Fig. 18).

Fig. 18

Structure of R14 & and color changes under UV light

A novel fluorescence receptor, N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide R15, incorporating both 8-aminoquinoline and 8-hydroxyquinoline units, was designed and synthesized for the dual detection of Zn²⁺ and Cd²⁺ [35]. The receptor's sensing capabilities in ethanol were evaluated. Excitation of R15 at 329 nm resulted in a weak emission peak at 410 nm with a quantum yield (ɸ) of 0.008. Introduction of Cd²⁺ ions led to a significant increase in fluorescence intensity (ɸ = 0.16) at the same excitation wavelength, indicating a 1:1 binding ratio. This fluorescence enhancement is attributed to the photoinduced electron transfer (PET) mechanism. In the presence of various interfering ions, Zn²⁺ caused a notable red shift in the emission spectrum to 486 nm (ɸ = 0.019), also exhibiting a 1:1 binding ratio. This red shift and fluorescence enhancement are due to the internal charge transfer (ICT) mechanism. The binding constants for R15 with Zn²⁺ and Cd²⁺ were determined to be 1.8 × 10⁴ and 9.8 × 10⁵, respectively (Fig. 19).

Fig. 19

Structure of R15 and its complex structure with Cd²⁺ and Zn²⁺

A coumarin-quinoline based receptor, R16, has been crafted for Zn²⁺ detection in a solvent mixture of CH₃CN:H₂O (1:3, v/v) buffered with 10 mM HEPES at pH 7.2 [36]. This yellow receptor R16 undergoes a visual color change to pale red and transitions from green to yellow under UV light. Absorption studies reveal that R16 alone exhibits a peak at 442 nm, indicative of intramolecular charge transfer (ICT) from the 7-diethylaminocoumarin to the 8-hydroxyquinoline unit. Adding Zn²⁺ ions to R16 results in a gradual decrease in the 442 nm absorbance, while a new peak emerges at 531 nm. Correspondingly, fluorescence at 516 nm diminishes, accompanied by a red-shift to a new emission band at 556 nm. This substantial 40 nm red-shift is attributed to the enhanced electron-withdrawing capability of the triazole-R16 complex upon Zn²⁺ coordination, which facilitates the ICT process from 7-diethylaminocoumarin to the triazole-modified R16. The detection limit for Zn²⁺ was determined to be 48.1 nM (Fig. 20).

Fig. 20

Structure of R16 and its sensing mechanism towards Zn²⁺

A fluorescence receptor, R17, derived from 2-(2-nitrostyryl)-8-methoxyquinoline, has been synthesized for the detection of Zn²⁺ in a CH₃CN–H₂O (9:1, v/v) medium [37]. The absorption spectrum of R17 shows a prominent band at 279 nm, attributable to the π–π* transition of the styrylquinoline moiety, and a weaker, broader band at 340 nm in CH₃CN. When excited at 319 nm, R17 exhibits a weak fluorescence emission at 480 nm, which is likely due to internal charge transfer (ICT) from the methoxy donor group to the nitrostyryl acceptor group. Upon the addition of Zn²⁺, there is a marked enhancement in fluorescence, explained by the inhibition of ICT from the methoxy group to the nitrostyryl group. The binding constant of R17 with Zn²⁺ is 8.35 × 10¹¹ M, with a 1:1 stoichiometry and a detection limit of 3.8 µM (Fig. 21).

Fig. 21

Structure of R17

The quinoline-based receptor 2-(hydroxymethyl)-4-methyl-6-((quinolinyl-8-imino)methyl)phenol (R18) exhibits exceptional selectivity and sensitivity for Zn²⁺ in a Tris–HCl buffer (50 mM, pH 7.54) within a THF-H₂O (9:1, v/v) medium [38]. When various metal ions are introduced to R18, Zn²⁺ uniquely induces a decrease in the absorption band at 338 nm and the appearance of a new band at 455 nm, accompanied by a noticeable color change from colorless to yellow. This new absorption peak is attributed to the coordination of Zn²⁺ with R18. The emission spectrum of R18, excited at 455 nm, shows a weak fluorescence at 515 nm with a quantum yield of Φ = 0.006. Upon addition of Zn²⁺, there is a 14-fold increase in fluorescence intensity, a red shift in the emission maximum to 565 nm, and an enhanced quantum yield of Φ = 0.045. R18 binds to Zn²⁺ through a 1:2 stoichiometry, forming a five-membered chelate ring with the aminoquinoline moiety via two nitrogen atoms and a six-membered chelate ring involving the Schiff base –C = N and Ar-OH groups. This chelation enlarges the conjugated system, thereby reducing the energy gap between the n and π* orbitals (Fig. 22).

Fig. 22

Structure of R18 and its colorimetric changes

Salicylaldimine and aminoquinoline-based derivatives R19a-d have been successfully synthesized and are reported for their selective detection of Zn²⁺ in an ethanol–water (9:1, v/v) medium [39]. When various metal ions, including Zn²⁺, Mn²⁺, Ba²⁺, Hg²⁺, Ni²⁺, Cu²⁺, Co²⁺, Pb²⁺, Mg²⁺, Cd²⁺, Fe²⁺, Cr³⁺, Al³⁺, Fe³⁺, Li⁺, K⁺, and Na⁺, are introduced to R19a-d, receptor R19a exhibits a significantly enhanced emission peak at 535 nm upon interaction with Zn²⁺ and at 439 nm with Al³⁺. Receptors R19b and R19c demonstrate remarkable selectivity towards Zn²⁺, showing no response to Al³⁺. The selective fluorescence enhancement by Zn²⁺ is attributed to chelation-enhanced fluorescence (CHEF) effects, where the deprotonation of the amido –NH and phenolic –OH groups initiates an internal charge transfer (ICT) process. The detection limits for Zn²⁺ with receptors R19a-b are found to range from 0.024 to 0.431 µM, with a 1:1 stoichiometry. The association constants for these sensors are estimated to range between 7.0 × 10³ and 1.2 × 10⁴ M⁻¹ (Fig. 23).

Fig. 23

Structure of R19a-d

A straightforward fluorescence receptor, R20, for detecting Zn²⁺ and Cd²⁺ was designed and synthesized by condensing phenanthrene-9,10-dione with 8-hydroxyquinoline-2-carbaldehyde in a mixture of ethanol and dichloromethane [40]. The sensing properties of receptor R20 were explored in the presence of various metal ions, including Al³⁺, Ca²⁺, Mg²⁺, Na⁺, Fe²⁺, Fe³⁺, Mn²⁺, Ni²⁺, Co²⁺, Cr³⁺, Cu²⁺, Hg²⁺, Pb²⁺, Zn²⁺, and Cd²⁺, in a water/DMF (7:3, v/v) solution. The free receptor R20 exhibits a primary emission band around 445 nm when excited at 340 nm. The presence of ions such as Fe²⁺, Fe³⁺, Ni²⁺, Mn²⁺, Co²⁺, Cu²⁺, Pb²⁺, and Cr³⁺ causes significant fluorescence quenching. Conversely, the addition of Zn²⁺ induces a pronounced shift in fluorescence from 445 to 520 nm. A more substantial redshift, from 445 to 580 nm, occurs upon the introduction of Cd²⁺. These considerable redshifts suggest that Zn²⁺ and Cd²⁺ interact with the electron donor sites in receptor R20, facilitating an effective internal charge transfer (ICT) (Fig. 24).

Fig. 24

Structure of R20 and the fluorescence studies of R20 with all the metal ions

A simple Schiff-base quinoline-based receptor, R21 ((E)-2-Methoxy-N-((quinolin-2-yl)methylene)aniline), has been reported for its selective, sensitive, and reversible detection of Zn²⁺ and Hg²⁺ in a DMSO–H₂O solution (1/99 v/v) [41]. The absorption maxima of R21 were observed at 293 nm, 292 nm, and 295 nm in DMA, DMF, and DMSO, respectively, corresponding to π–π* transitions and intramolecular charge transfer (ICT) processes. The fluorescence intensity of receptor R21 gradually decreased and red-shifted to 473 nm with increasing DMSO fraction in the mixed solvent system. The strong emission of R21 in polar solvents can be attributed to π*–π transitions of non-aggregated molecules. In contrast, the decreased fluorescence intensity and red shift were due to the aggregation-caused quenching effect, shifting the fluorescence band from 413 to 473 nm. Upon the addition of Zn²⁺ to the R21 solution, a remarkable enhancement in fluorescence intensity was observed, along with the generation of new peaks at 565 nm. Similarly, the addition of Hg²⁺ triggered emission at 530 nm (yellowish-green), slightly less intense than that observed with Zn²⁺. The detection limits for Zn²⁺ and Hg²⁺ with R21 were calculated to be 0.011 μM and 0.040 μM, respectively (Fig. 25).

Fig. 25

Structure of R21

Carboxamidoquinoline-based fluorescence probes R22a-b were synthesized and reported as selective sensors for Zn²⁺ in a methanol–water solution (1:9 v/v) with an ionic strength of 0.1 (KCl). These probes demonstrated selectivity for Zn²⁺ over other interfering metal ions such as Ag⁺, Ca²⁺, Mg²⁺, Pb²⁺, Na⁺, K⁺, and Fe³⁺ [42]. The presence of Cu²⁺, Co²⁺, and Ni²⁺ resulted in fluorescence quenching of the receptors, attributed to energy transfer from the photo-excited quinoline ring to the empty d-orbitals of these metal ions. Upon the addition of Zn²⁺, R22a-b exhibited a significant fluorescence enhancement due to the deprotonation of the carboxamido group. In living cells, the blue-green emission gradually increased, indicating that the receptor is membrane-permeable and capable of signaling the presence of intracellular Zn²⁺ (Fig. 26).

Fig. 26

Structure of R22a-b and its cell imaging studies

A carboxamidoquinoline-based fluorescence receptor, R23, featuring an alkoxyethylamino chain, was designed to evaluate its sensing capabilities for various metal ions in a Tris–HCl (0.01 M) solution (methanol/water, 1:9 v/v, pH 7.22) [43]. Upon the addition of increasing amounts of Zn²⁺ to R23, an approximately eightfold increase in fluorescence quantum yield and a 75 nm red-shift from 440 to 515 nm (Φ = 7.96) in fluorescence emission were observed, along with a noticeable blue-green emission visible to the naked eye. The association constant and stoichiometry for the R23-Zn²⁺ complex were determined to be 6.7 × 10⁶ M⁻¹ and 1:1, respectively. In acidic conditions, R23 exhibited no fluorescence emission due to the protonation of its amino group. However, as the pH increased from 6.1 to 11.8, R27 showed the highest sensing ability under physiological pH conditions (Fig. 27).

Fig. 27

Structure of R23

A novel quinoline-based fluorescent receptor, R24, has been reported for the selective sensing of Zn²⁺ in an aqueous solution (ethanol/water = 1:1, v/v) [44]. Receptor R24 exhibited an absorption band at 235 nm and a broad band around 311 nm. Upon the addition of Zn²⁺, the absorbance at 240 nm and 311 nm decreased, while new absorption peaks appeared at 262 nm and 363 nm, with isosbestic points at 250 nm and 331 nm. In the fluorescence spectrum, the free receptor showed an emission band at 407 nm (λ_ex = 330 nm; Φ = 0.018). Introducing Zn²⁺ to receptor R24 resulted in a remarkable red-shifted enhanced fluorescence from 407 to 499 nm (92 nm) with a quantum yield of 0.082. This enhanced fluorescence is attributed to the deprotonation process of carboxamidoquinoline and the internal charge transfer (ICT) mechanism. The intramolecular electron-transfer process is activated upon metal ion binding, leading to increased fluorescence emission (Fig. 28).

Fig. 28

Structure of R24

A ratiometric fluorescent sensor, R25, based on carboxamidoquinoline with a carboxylic acid group, has been synthesized and reported for the selective detection of Zn²⁺ in a tris–HCl buffer (ethanol/water = 1:1, v/v, pH 7.24) medium [45]. Among sixteen metal ions tested, receptor R25 exhibits exceptional selectivity towards Zn²⁺, displaying selective fluorescence responses. With the incremental addition of Zn²⁺ into R25, the emission band at 402 nm decreases while that at 484 nm increases (13-fold; 82 nm red-shift), with an iso emission point appearing near 411 nm. The absorption spectrum of receptor R25 reveals an absorption peak at 239 nm and a broad band around 306 nm. Absorption experiments demonstrate a 43 nm red-shift from 306 to 349 nm upon zinc binding. The stoichiometry and detection limit of R25-Zn²⁺ were calculated to be 1:1 and 27 µM, respectively. Additionally, R25 has been successfully utilized for determining Zn²⁺ levels in both tap and river water samples (Fig. 29).

Fig. 29

Structure of R25

A novel quinoline-based fluorescence receptor, R26, was developed as a dual sensor for acetate (AcO⁻) and fluoride (F⁻) among various anions in a DMSO solvent medium [46]. Upon the addition of F⁻ and AcO⁻ to R26 in DMSO, a significant color change from light yellow to orange-brown was observed. This color change is attributed to the intramolecular charge transfer (ICT) process occurring between the phenolic oxygen and the electron-withdrawing quinoline ring, facilitated by the formation of a hydrogen-bonded complex between the hydroxyl groups of R26 and F⁻ and AcO⁻. The free receptor exhibited two absorption bands at 303 nm (-CH = N; π-π*) and 400 nm, indicative of the intramolecular charge transfer (ICT) mechanism (ketoamine–phenolimine). Upon the addition of F⁻ and AcO⁻, a new charge transfer band at approximately 530 nm appeared, indicating the formation of a host–guest complex between the receptor and the anions. The binding constants and stoichiometry of R26 with F⁻ and AcO⁻ were calculated to be 2.39 × 10⁵ M⁻¹ (F⁻), 2.18 × 10⁵ M⁻¹ (AcO⁻), and 1:1, respectively (Fig. 30).

Fig. 30

Structure of R26

Excited state intramolecular proton transfer mechanism

In the ESIPT mechanism, molecules exhibit dual emission characteristics. The excited enol form (E*) leads to short-wavelength (normal) emission, while the excited keto form (K*) results in longer wavelength emission (ESIPT emission). The spectral properties of ESIPT fluorophores are influenced by factors such as the donor and acceptor units within the molecule, hydrogen bonding behavior, the acidity or basicity of the solvent, and the rotamerization process. Additionally, the fluorescence properties of ESIPT fluorophores can be adjusted by altering the surrounding medium (Fig. 31).

Fig. 31

Excited state intramolecular proton transfer mechanism

A novel fluorescence receptor, R27, based on ESIPT (Excited-State Intramolecular Proton Transfer), has been developed for the detection of HOCl [47]. When the free receptor R27 is excited at 360 nm, it exhibits a prominent emission band at 515 nm, attributed to the ESIPT process, resulting in a large Stokes shift of 155 nm. Upon the addition of NaOCl, the fluorescence intensity at 515 nm significantly decreases, accompanied by the appearance of a new emission peak at 585 nm. The detection limit for HOCl was calculated to be 40 nM. Receptor R27 holds potential for monitoring both exogenous and endogenous HOCl and can be localized in the endoplasmic reticulum of living cells (Fig. 32).

Fig. 32

Structure of R27

A straightforward flavone-based receptor, R28, was synthesized to leverage the Excited-State Intramolecular Proton Transfer (ESIPT) process for ratiometric detection of hydrogen polysulfides [48]. The receptor exhibits high selectivity and sensitivity towards hydrogen polysulfides, boasting a low detection limit of 0.63 µM. Featuring a 2-fluoro-5-nitrobenzoic acid group, R28 effectively inhibits the intramolecular ESIPT process, resulting in the blue fluorescence of the neighboring naphthalene unit. In the presence of H₂S, the enol form of the probe converts to the conjugated keto form, leading to a substantial 90 nm red-shift in fluorescence emission from 450 to 540 nm. The receptor has been successfully employed for exogenous H₂S detection and imaging via dual emission channels in living Hela cells (Fig. 33).

Fig. 33

Structure of R28

A novel naphthalimide-based receptor, R29, was devised, synthesized, and disclosed for the ratiometric detection of Al³⁺ through the inhibition of ESIPT in a H₂O/CH₃CN (1:9; v/v) solvent system [49]. In the absorption spectrum, R29 exhibits two distinct charge transfer bands at 340 nm and 460 nm. Upon excitation at 460 nm, R29 displays two emission bands at 510 nm and 610 nm. The introduction of Al³⁺ into R29 induces a color change from orange to yellow, with the charge transfer band at 460 nm increasing ratiometrically. Under UV light, R29-Al³⁺ emits blue-green light, transitioning from yellow, and displays an enhanced emission band at 540 nm. Furthermore, the receptor enables the ratiometric detection of F⁻, manifesting a color change from orange to purple, with an emission band observed at 570 nm. The detection limits for receptor R29 with Al³⁺ and F⁻ were determined to be 32 nM and 75 µM, respectively (Fig. 34).

Fig. 34

Structure of R29 and its visual and fluorescence color change

C. Shang and fellow researchers introduced a fluorescence receptor, R30, based on hydroxyanthraquinones, and investigated the ESIPT mechanism by altering electronic groups [50]. The maximum absorption peaks of these receptors experienced a red shift. Notably, the addition of electron-withdrawing substituents induced a substantial Stokes shift. Analyses of FMOs and NBO population confirmed the charge recombination around the proton donor and acceptor, strengthening hydrogen bonding and providing further momentum for ESIPT behavior (Fig. 35).

Fig. 35

Structure of R30

A carbazole-conjugated Schiff base serves as a sensitive fluorescent receptor (R31) for detecting Al³⁺ ions in an ethanol–water (1:1, v/v) medium [51]. The receptor exhibits a new absorption band at 531 nm, arising from the transfer of lone pairs of electrons from nitrogen/oxygen of the receptor to the metal ion. Initially, the receptor emits weak fluorescence due to the isomerization of the C = N bond in the excited state via excited-state intramolecular proton transfer (ESIPT). However, upon the introduction of Al³⁺ ions, enhanced fluorescence emission is observed, indicating the disruption of the ESIPT feature. The association constant, binding mode, and detection limit of receptor R31 with Al³⁺ were calculated to be 5 × 10⁴ M⁻¹, 1:1, and 2.59 µM, respectively (Fig. 36).

Fig. 36

Structure of R31 and its sensing mechanism towards Al³⁺

A novel Schiff base fluorescence receptor, R32, namely (E)-4-methyl-2-((2-(9-(naphthalen-1-yl)-8-(thiophen-2-yl)-9H-purin-6-yl)hydrazono)methyl)phenol, was designed and presented for the detection of Al³⁺ in DMSO/H₂O (9/1, v/v, pH = 7.4) [52]. Initially non-fluorescent, the receptor exhibits an enhanced emission intensity at 462 and 488 nm upon interaction with Al³⁺. This increase in fluorescence of receptor R32 may be ascribed to the inhibition of the PET and ESIPT processes induced by Al³⁺. The detection limit and binding mode were determined to be 82 nM and 1:1, respectively. R32 efficiently detects trace amounts of Al³⁺ in test strips and living HeLa cells (Fig. 37).

Fig. 37

Structure of R32 and its fluorescence images

A Schiff base fluorescence receptor, R33, incorporating coumarin was synthesized to facilitate an ESIPT transfer process for detecting Hg²⁺ and Pb²⁺ ions in a HEPES buffer solution [53]. Upon the addition of Hg²⁺, the yellow color of the receptor shifted to colorless and exhibited very weak cyan fluorescence emission at 470 nm. This diminished fluorescence emission can be attributed to the phenolic-oxygen atoms and imine nitrogen distributing the lone pair of electrons, thereby inhibiting ESIPT and activating PET processes. The detection limits were determined to be 8.3 and 10.5 nM for Hg²⁺ and Pb²⁺ ions, respectively (Fig. 38).

Fig. 38

Structure of R33 and sensing test strips

A novel Schiff base receptor, R34, featuring benzimidazole conjugation, 1-[[(1H-1,3-benzodiazol-2-yl)imino]methyl]naphthalen-2-ol, demonstrated remarkable selectivity towards Cu²⁺ and exhibited a robust fluorescence enhancement at 504 nm in a CH₃CH₂OH-PBS (v/v = 1:1, pH = 7.0) mixed solution [54]. Initially, R34 displayed very weak fluorescence emission at 365 nm. However, with an increase in water content in R34, the fluorescence emission intensity gradually rose from 497 to 504 nm. The binding stoichiometry and detection limit were calculated to be 2:1 and 0.814 nM, respectively (Fig. 39).

Fig. 39

Structure of R34

A dinitrophenyl-based Schiff base fluorescence receptor R35 act as an efficient detection of Zn²⁺ in a DMSO-H₂O solvent mixture. Due to the ESIPT mechanism the receptor shows a weak fluorescence emission at 530 nm when excites the receptor at 340 nm [55]. Upon the addition of Zn²⁺ into R35 an enhanced fluorescence was noticed at 530 nm. The enhanced fluorescence emission is due to the inhibition of the excited state intramolecular proton transfer mechanism. The red-colored receptor solution turned yellow color in the presence of zinc ions. The binding constant, stoichiometry, and detection limit were found to be 6.35 × 10⁷ M⁻¹, 1:1, and 0.11 nM, respectively (Fig. 40).

Fig. 40

Structure of R35

Dual detection-based hydrazone Schiff base fluorescence receptor R36 has been synthesized and characterized [56]. By adding Cu²⁺ into R36 its shows 410 nm and the decrease of fluorescence emission intensity at 532 nm with an appearance of emission band at 570 nm. In the presence of F⁻ ions the receptor shows a new absorption band at 513 nm and an emission band at 532 nm. The –NH unit in the Schiff base receptor is the proper H-bond donor which can act as a selective sensor for F⁻ ions. The detection limits of R36 towards Cu²⁺ and F⁻ were calculated to be 3.51 µM and 3.26 µM, respectively with a 2:1 demultiplexer (Fig. 41).

Fig. 41

Structure of R36

A novel Schiff base receptor, R37, has been developed for the detection of F⁻ and tryptamine ions in a DMSO-H₂O (9:1, v/v) medium, utilizing both colorimetric and fluorimetric methods [57]. In the presence of tryptamine, R37 exhibits enhanced fluorescence at 433 nm, while a band at 533 nm decreases in intensity due to the inhibition of ESIPT. Conversely, in the presence of fluoride ions, the intensity of the band at 430 nm increases, while the band at 555 nm decreases, owing to the ESIPT mechanism. Fluorescence analysis was conducted in live cell studies using HeLa cells and Zebrafish embryos (Fig. 42).

Fig. 42

Structure of R37 and its sensing mechanism towards F⁻

A fluorescence Schiff base receptor, R38, has been developed and synthesized for the selective detection of N₂H₄ and CN⁻ ions [58]. Hydrazine leads to the quenching of the bright green fluorescence of R38, while cyanide induces a change in the bright green fluorescence to an orange-red color. The receptor operates through the ESIPT process and a resonance-assisted hydrogen bonding-coupled structure. Upon coordination with N₂H₄ and CN⁻, the ESIPT process of R38 is disrupted. In test strip studies, R38 demonstrates significant color changes upon interaction with N₂H₄ and CN⁻ ions (Fig. 43).

Fig. 43

Structure of R38

An efficient fluorescence receptor R39 has been developed by using Bis(2-aminophenyl) ether and salicylaldehyde [59]. The receptor is well characterized with FTIR, ¹H NMR, ¹³C NMR, and mass spectroscopic analysis. Upon the addition of Al³⁺ ions into R39, fluorescence turn-on at the large Stokes shifted wavelength 528 fold. The turn-on fluorescence is due to the electron-releasing-substituent on the phenol rings and exhibits an ESIPT mechanism. The detection limit and stoichiometry were calculated to be 5.48 nM and 1:1 binding mode (Fig. 44).

Fig. 44

Structure of R39

Fluorescence resonance energy transfer (FRET)

A fluorescent probe based on the FRET mechanism can link two fluorophores (donor and acceptor) within a single molecule. The donor (D) absorbs radiation at the excitation wavelength and transfers this energy to the acceptor (A), which then emits it at a longer wavelength. If the emission spectrum of the donor overlaps with the absorption spectrum of the acceptor, non-radiative energy transfer from D to A can occur. When D is excited, the fluorescence emission of A can be observed as a result of this energy transfer (Fig. 45).

Fig. 45

Fluorescence resonance energy transfer

A quinoline-conjugated benzothiazole derivative linked with rhodamine-6G receptor R40 act as an efficient FRET-based single molecular switch for detecting Fe³⁺ ions in a CH₃OH/H₂O solution (2/3, v/v, pH = 7.2) [60]. It exhibits an immediate fluorescence ratiometric response specific to Fe³⁺, enabling easy naked-eye detection of Fe³⁺. The R40 shows high selectivity for Fe³⁺ compared to other environmentally significant cations, including Fe²⁺. The ratiometric response is primarily driven by the FRET mechanism. Coordination of Fe³⁺ with the nitrogen atom of the benzothiazole moiety, the nitrogen and oxygen atoms of hydroxyquinoline, and the nitrogen atom of the rhodamine–ethylene diamine moiety, along with electron transfer from the benzothiazole, leads to the opening of the spiro ring. The detection limit and binding mode of the receptor with Fe³⁺ were determined to be 0.53 nM and 1:1, respectively (Fig. 46).

Fig. 46

Structure of R40 and its sensing mechanism with Fe³⁺ ions

Y. Wang and his team reported that hydrazone-bearing 1,8-naphthalimide and pyrrole moieties (R41) act as the first ratiometric fluorescent sensor for Cu²⁺, utilizing hydrolysis via Cu²⁺-promoted electrophilic substitution [61]. In the presence of Cu²⁺ ions in a CH₃CN/H₂O solution (9:1, v/v, pH = 7.40), receptor R41 shows a decrease in absorbance at 480 nm and a red shift from 335 to 350 nm, changing its color from orange to colorless. R41 alone exhibits a significant red fluorescence emission band at 620 nm. Upon the addition of Cu²⁺, fluorescence intensity increases, and a new emission band appears at 545 nm, distinguishing Cu²⁺ from other cations such as Ag⁺, Al³⁺, Ca²⁺, Cd²⁺, Co²⁺, Cr³⁺, Fe³⁺, Hg²⁺, K⁺, Mg²⁺, Mn²⁺, Na⁺, Ni²⁺, Pb²⁺, and Zn²⁺. The detection limit of R41 for Cu²⁺ ions is 1.50 µM, with a binding mode of 1:1. Additionally, receptor R41 can be used to image intracellular Cu²⁺ in living cells (Fig. 47).

Fig. 47

Structure of R41 and R41-Cu²⁺ ions

Shen and colleagues created a ratiometric and colorimetric fluorescent receptor, R42, that specifically detects SO₃²⁻/HSO₃⁻ ions in an EtOH/PBS buffer solution (10 mM, pH 7.4, v/v = 3/7) [62]. When excited at 405 nm, it exhibits a fluorescence shift from red to green, with a response time of less than 3 min. R42 features a large Stokes shift and a broad emission window, effectively preventing interference between the two fluorescence emission channels. Furthermore, its excellent luminescence properties enabled its initial use as a fluorescent donor for a FRET receptor, enhancing the diversity of donors available. The detection limit for R42 was determined to be 39 nM. The receptor is capable of detecting both exogenous and endogenous sulfites in living cells, making it suitable for use in cellular and mouse imaging (Fig. 48).

Fig. 48

Structure of R42 and its sensing mechanism with SO₃²⁻ ions

A novel ratiometric fluorescent receptor, R43, has been synthesized for detecting Hg²⁺ ions in environmental and various biological samples. The receptor employs a covalent connection of two fluorophores via lipoic acid to enable fluorescence resonance energy transfer (FRET) [63]. In the molecular structure of receptor, acridone serves as the energy donor, 1,8-naphthalimide functions as the energy acceptor, and a dithioacetal group acts as the reaction site for Hg²⁺. The intact receptor predominantly displays green fluorescence from the 1,8-naphthalimide acceptor moiety. Upon exposure to Hg²⁺ ions, the dithioacetal linkage between acridone and 1,8-naphthalimide is cleaved, disrupting FRET and resulting in a bright blue fluorescence emission from acridone. This process allows for the ratiometric fluorescent detection of Hg²⁺. The detection limit is calculated to be 30 nM. Additionally, this receptor has been successfully applied to detect Hg²⁺ in actual samples and to image a variety of organisms, demonstrating its broad application potential (Fig. 49).

Fig. 49

Structure of R43

Liu et al., reported a novel ratiometric fluorescent receptor R44 based on 1,8-naphthalimide-rhodamine for the selective & sensitive detection of Fe³⁺/Hg²⁺ ions in ethanol/PBS buffer (1:1, v/v, pH = 7.4) solution [64]. Receptor R44 with Hg²⁺ ions exhibits typical FRET signal from pyridine-naphthalimide moiety to rhodamine moiety with the lowest detection limit of 2.72 × 10^–6 M. However, in the presence of Fe³⁺ ions the receptor R44 shows ratiometric detection behavior via PET process combined with the classical ring-opening sensor system with the detection limit of 5.7 × 10^–7 M. Receptor R44 emitted bright yellow fluorescence in solid state & the maximum wavelength was 538 nm. The dye-doped Si-nanoparticles emit strong green fluorescence, the maximum fluorescence emission wavelength was 495 nm & further rainforced the AIE effect (Fig. 50).

Fig. 50

Structure of R44 and its sensing mechanism with Hg²⁺ & Fe³⁺ ions

N-Z Xu & coworkers designed & synthesized a novel receptor R45 based on 1,8-naphthalimide group & rhodamine B for the selective & sensitive detection of Hg²⁺ ions [65]. Upon addition of Hg²⁺ ions to receptor R45 reveals a significant color change from colorless to pink & a light to orange fluorescence change. The receptor R45 was selectively sensed with Hg²⁺ based on the fluorescence resonance energy transfer (FRET) mechanism. receptor R45 shows a typical FRET signal from the 1,8-naphthalimide group to the rhodamine group, a new emission peak appears at 585 nm & the emission peak at 381 nm decreases in the fluorescence spectrum with 1:1 binding stiochiometry. The detection limit was found to be 0.059 µM & the calculated association constant was 2.75 × 10⁵ M⁻¹ (Fig. 51).

Fig. 51

Structure of R45 and its sensing mechanism with Hg²⁺ ions

A Rhodamine B-Quinoline conjugate receptor R46 selectively detects Bi³⁺ by colorimetric and fluorescence methods based on CHEF assisted FRET process in DMSO: water (1:1, v/v) [66]. Upon the gradual addition of Bi³⁺ the absorbance at 322 nm increases (1 µM) and increasing the concentration (> 1 to 1000 μM) of Bi³⁺ gradually decreases this absorbance while a new band that appears at 566 nm. A weak fluorescence emission was noticed for free receptor at 597 nm upon the excitation of 525 nm. In the presence of Bi³⁺ the emission intensity along with ~ 30 fold increase was noticed at 597 nm (Φ = 0.59). The binding constant, stoichiometry and detection limit of R46 with Bi³⁺ was calculated to be 2.1 × 10⁵, 1:1 and 0.05 μM, respectively. Receptor R46 can efficiently images intra cellular Bi³⁺ in SiHa cell line. (Fig. 52).

Fig. 52

Structure of R46

Rhodamine-based fluorescent receptor R47 has been developed for the selective and sensitive detection of Pd²⁺ metal ions in aqueous media MeCN-H₂O (50:50 v/v, 25 °C) [67]. A rhodamine-BODIPY Förster resonance energy transfer (FRET)-pair receptor R47 has been incorporated with a piperazine linker and an O-N-S–N pod and ligand for specific recognition of Pd²⁺ ion. A bright strong green emission was observed for all cations except Au³⁺ and Pd²⁺ in the UV light under 360 nm. The emission of Au³⁺ was quenched after binding to R47; it did not trigger the opening of lactam to give the characteristic red emission of rhodamine; only Pd²⁺ was able to “turn-on” R47 to give intense red emission. Upon reacting with Pd²⁺, the green colour emission at 515 nm decreased while the red colour emission at 600 nm was increased. Imaging of Pd²⁺ and GSH in live A549 cells was demonstrated, indicating the utility of receptor as a reliable analytical tool for the detection in aqueous media and cell imaging of Pd²⁺ and biothiols (Fig. 53).

Fig. 53

Sensing mechanism of R47 towards Pd²⁺ and its fluorescence bioimaging

A FRET based ratiometric fluorescent receptor R48 containing benzoxadiazole moieties and coumarin moieties bound via ethylenediamine have been reported for the detection of ClO⁻ ions [68]. Receptor has excellent selectivity and anti-interference ability toward ClO⁻, and the ratio of fluorescence intensity (I_{471 nm}/I_{533 nm}) has a very good linear relationship with the concentration of ClO⁻, with a wide linear range (2.5 – 1750 μM) and low detection limit (0.887 μM). The receptor have successfully applied it for the quantitative detection of ClO⁻ in water samples in daily life. The blue/green value (B/G) of this color change also shows a very good linear relationship to ClO⁻ (5.0–1000 μM). Further the receptor R48 has also been successfully used for test strip detection and quantitative detection of ClO⁻ in actual samples through smartphone-based fluorescence image analysis, and this method can provide faster, more convenient and more accessible detection (Fig. 54).

Fig. 54

Structure of R48 and its sensing mechanism with ClO⁻ ions

Aggregation Induced Emission

The primary cause of the AIE phenomenon is the restriction of intramolecular motion, rotation, or vibration (RIM, RIR, or RIV) within aggregates. AIE-active molecules exhibit weak emission in solution due to free intramolecular motions, but they become highly emissive upon aggregation in a suitable environment through the activation of RIM, RIR, or RIV mechanisms in the excited state. This unusual fluorescence behavior allows the AIE phenomenon to be effectively used in designing fluorescent probes with appropriate chelating groups for detecting metal ions. The aggregation of AIE probes can be modulated by metal ions through electrostatic interactions, coordination interactions, or the effects of polarity and viscosity (Fig. 55).

Fig. 55

Aggregation induced emission

Highly fluorescent aggregation induced emission based 1, 8-naphthalimide- sulfamethizole sensor R49 have been reported for Hg²⁺ and Ag⁺ ions [69]. Aggregation induced emission caused by hydrophobic nature of naphthalimide fluorogenic moiety in DMSO: water (1:99 v/v, pH 7.2, HEPES buffer). Upon the addition of various metal ions, Hg²⁺ ions shows a increases in absorbance at 267 nm and 343 nm with a slight red shift (hypochromic effect). An excimeric group obtained from the intramolecular interaction between the naphthalimide moieties in the completion of R49 with Hg²⁺ ion. Due to this reason Sensor R49 emission band at 390 nm quenched and a new intensity band appeared at 483 nm in the presence of Hg²⁺ ions. The sensor R49 -Hg²⁺ coordination restricting the free rotations of the R49 and increases the rigidity of the molecular assembly, resulting a enhanced fluorescence intensity at 483 nm. Further, significantly enhancing fluorescence intensity was observed by the increasing addition of Hg²⁺ ions. Mercury ions induce more aggregation of the R49 -Hg²⁺ complex thereby facilitates the aggregation induced emission enhancement behavior of the R49. Sensor R49 sensitively detects Hg²⁺ ions and the calculated detection limit of R49-Hg²⁺ ions is 14.7 nM (Fig. 56).

Fig. 56

Structure of R49

A new fluorescent sensor R50a-b based on sulfonamidospirobifluorenes was synthesized and reported for the selective detection of Hg²⁺ ions in DMSO/HEPES buffer mixture [70]. Out of twenty metal ions, sensor R50a-b only shows an excellent selectivity towards Hg²⁺ ions and showed a selective fluorescence quenching (107-folds). The sulfonamide group coordinates to Hg²⁺ ions that direct to an aggregation of such complex via the face-to-face stacking of the spirobifluorene cores. At neutral pH, the sulfonamide group coordinates with Hg²⁺ ions and could promote a deprotonation of the –NH group in R50a-b. The detection limits of R50a-b with Hg²⁺ ions were found to be 10.4 nM and 103.8 nM for the derivatives bearing two and four sulfonamide groups, respectively (Fig. 57).

Fig. 57

Structure of R50a-b

A chromone-based ratiometric fluorescent receptor R51 was developed for the selective detection of Hg(II) in a semi-aqueous solution based on aggregation-induced emission (AIE) and chelation-enhanced fluorescence (CHEF) effect [71]. The receptor R51 fluoresced significantly at 498 nm in its aggregated state, and when chelated with Hg²⁺. The stoichiometry, association constant and detection limit of R51 with Hg²⁺ was found to be 1:1, 9.10 × 10³ M⁻¹ and 22.47 nM, respectively without interference from other interfering ions. The FTIR, ESI mass, and DFT-based computational studies investigated the binding mechanism of receptor R51 with Hg²⁺. Taking advantage of its AIE characteristics, the receptor R51 was successfully applied for bio-capability analysis in Caenorhabditis elegans imaging of Hg²⁺ in a living model (Fig. 58).

Fig. 58

Structure of R51

Y. Li et al. reported [72] a novel fluorescence receptor R52 for selective and sensitive detection for Hg²⁺ and CN⁻ ions in DMF-H₂O (13:12, v/v). Receptor R52 shows a nonemissive spectrum in a pure organic solvent (DMF) & low concentrated aqueous system. When the water content is increased to 60%, significantly the fluorescence emission band at 650 nm increased and in 80% water the emission intensity band reached its maximum (120 fold). Slight decrease of fluorescence intensity was observed when adding further water in R52. This is due to the formation of amorphous aggregates. The emission intensity of R52 gradually inclined and reaches the maximum along with a small bathochromic shift (50 nm) upon the addition of Hg²⁺ ions. Under a UV lamp (360 nm), R52-Hg²⁺ complex results a strong red fluorescence and the calculated detection limit to be 6.6 nM. The enhancement of fluorescence is due to the aggregation induced by coordination of thymine units with Hg²⁺ ions (Fig. 59).

Fig. 59

Structure of R52

A novel aggregation-induced emission based receptor R53 designed [73], synthesized and reported for selective recognition of Hg²⁺ ions in a mixture of CH₃CN:H₂O (60%). Receptor R53 further used to quantitatively measure the bioaccumulation of Hg²⁺ within a small invertebrate, D. carinata. When excite receptor R53 at 350 nm the emission intensity increased from 0.17 to 1038.6 upon the gradual addition of Hg²⁺ ions (6100-fold). D. carinata alone shows no fluorescence signals and when incubated in R53 showed blue fluorescence (460–500 nm). In the presence of Hg²⁺ ions, D. carinata- R53 showed red fluorescence in the red channel in the 570–610 nm wavelength range. From the fluorescent microscopy studies it clearly recognizes in vivo dispersion and distribution of Hg²⁺ in D.carinata (Fig. 60).

Fig. 60

Structure of R53

A novel 8-hydroxyquinoline functionalized pillar[5]arene receptor R54 was synthesised and sensor selectively recognize toxic Hg²⁺ ions selectively based on AIE fluorescence mechanism in aqueous solution [74]. Receptor R54 almost shows non fluorescence in pure organic system (DMF). Once increasing the water content, R54 displays strong fluorescence emission intensity at 410 nm (7.88-fold) due to aggregation of fluorescence. Upon the addition of various metal ions into R54, Hg²⁺ ions could significantly quench the fluorescence over other ions at 410 nm. Under the UV lamp the fluorescence color of R54 (20% H₂O) changed from blue to colorless upon the addition of Hg²⁺ ions. The detection limit of R54 towards Hg²⁺ ions was calculated to be 0.24 nM. Further based on the above results, Hg²⁺ detection test kit was prepared by using R54 sensor on a silica gel plate and the test kit could detect Hg²⁺ ions more conveniently and effectively (Fig. 61).

Fig. 61

Structure of R54

A series of novel pyridopyrazine derivatives based receptor R55a-d were synthesized and developed for selective and sensitive detection for Hg²⁺ ions in H₂O-CH₃CN mixture [75]. Receptor R55a showed highly twisted conformation with no π-π stacking interactions. All the receptor R55a-d are showed a weak fluorescence emission in CH₃CN solution. In higher water fractions receptor R55a-d displayed a strong enhancement of emission intensity with slight red shift in emission maxima. Pyridopyrazine derivatives of receptor R55a-d bearing electron withdrawing biphenyl rings showed “turn-on” whereas receptor R55a-d bearing electron donating biphenyl rings showed “turn-off” fluorescent response towards Hg²⁺ ions in aqueous media. The detection limits of receptor R55a-d towards Hg²⁺ were found to be in submicromolar range. The other competitive metal ions such as Na⁺, K⁺, Mg²⁺, Ca²⁺, Ba²⁺, Cr³⁺, Fe³⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, Ag⁺, Zn²⁺, Cd²⁺, Al³⁺ and Pb²⁺ didn’t shows a fluorescence response with receptor R55a-d (Fig. 62).

Fig. 62

Structure of S55a-d

An aggregation induced emission based receptor R56 ((E)-4-((2-hydroxy-5 methoxybenzylidene)amino)benzoic acid) was synthesized through facile Schiff base condensation and characterized by various spectral techniques [76]. The as-prepared compound represented a typical aggregation induced emission behavior in aqueous solution and exploited as a turn-off fluorescent sensor for Fe³⁺ detection in THF-H₂O system (3:7, v/v) with high sensitivity and selectivity. The mechanism of the fluorescence quenching was intensively studied, which was attributed to both dynamic quenching and inner filter effect. The fluorescence probe displayed a highly broad dynamic response range (0.5–500 μM) for selective detection of Fe³⁺ with a limit of detection of 0.079 μM. The proposed method was successfully employed for detection and quantification of Fe³⁺ in human urine samples and proved to have potential for practical applications in biological field (Fig. 63).

Fig. 63

Structure of R56

Conclusion

Fluorescent chemosensors have revolutionized the field of toxic ion detection due to their remarkable sensitivity, selectivity, and rapid response capabilities. This review has highlighted the significant advancements in the development of chemosensors based on these mechanisms, showcasing their design principles, operational mechanisms, and practical applications in detecting environmentally and biologically relevant toxic ions. Each of the five mechanistic approaches offers unique advantages and has led to the creation of highly specialized sensors. PET-based chemosensors are celebrated for their ability to detect metal ions with high sensitivity due to their electron transfer properties. FRET-based sensors excel in applications requiring conformational sensitivity and ratiometric measurements, providing reliable and precise detection of ions like Zn²⁺, Cu²⁺ and Hg²⁺. ICT sensors, with their wavelength-shifting capabilities, are particularly effective for detecting ions, benefiting from the significant electronic perturbations induced by ion binding. AIE sensors, exploiting the unique properties of aggregation-induced fluorescence, have opened new avenues for sensing in complex biological and environmental samples. ESIPT sensors, with their dual-emission characteristics, offer high sensitivity and ratiometric detection, making them suitable for detecting a variety of ions under diverse conditions.

Despite these advances, challenges remain in the development of fluorescent chemosensors. Issues such as background interference, sensor stability, and selectivity in complex matrices need to be addressed. Detecting toxic ions at very low concentrations, which are often found in real-world environmental and biological samples, is a significant challenge. The need for real-time, in situ monitoring of toxic ions is growing, but current technologies often lack the speed and efficiency required for such applications. Moreover, the integration of these sensors into practical devices for field use and their scalability for industrial applications require further research and innovation. The future of fluorescent chemosensors lies in addressing current limitations and expanding their applicability. Several promising avenues for future research and development include improving selectivity and sensitivity, multiplexed sensing, and exploration of new mechanisms, designing biocompatible and environmentally sustainable chemosensors. The field of fluorescent chemosensors for detecting toxic ions can be significantly extended by integrating advanced technologies such as portable sensors to develop compact, user-friendly devices for on-site detection and monitoring. Designing multifunctional chemosensors capable of detecting multiple toxic ions simultaneously will improve efficiency and reduce analysis time. The continued innovation in the design and application of fluorescent chemosensors holds great promise for the future of toxic ion detection.