molecules

Review
Recent Progress on Fluorescent Probes in Heavy Metal
Determinations for Food Safety: A Review
Liqing Lai 1 , Fang Yan 1 , Geng Chen 2 , Yiwen Huang 2 , Luqiang Huang 1, * and Daliang Li 1, *

1 The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and
Products of the State Oceanic Administration, Fujian Key Laboratory of Special Marine Bioresource
Sustainable Utilization, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China;
lqinglai7@163.com (L.L.); yanfang8270@163.com (F.Y.)
2 Fujian Fishery Resources Monitoring Center, Fuzhou 350117, China; cg395395@126.com (G.C.);
m15259109300@163.com (Y.H.)
* Correspondence: biohlq@fjnu.edu.cn (L.H.); daliangli@fjnu.edu.cn (D.L.);
Tel.: +86-13459403113 (L.H.); +86-13696871978 (D.L.)

Abstract: One of the main challenges faced in food safety is the accumulation of toxic heavy metals
from environmental sources, which can sequentially endanger human health when they are consumed.
It is invaluable to establish a practical assay for the determination of heavy metals for food safety.
Among the current detection methods, technology based on fluorescent probes, with the advantages
of sensitivity, convenience, accuracy, cost, and reliability, has recently shown pluralistic applications
in the food industry, which is significant to ensure food safety. Hence, this review systematically
presents the recent progress on novel fluorescent probes in determining heavy metals for food safety
over the past five years, according to fluorophores and newly emerging sensing cores, which could
contribute to broadening the prospects of fluorescent materials and establishing more practical assays
for heavy metal determinations.

Keywords: fluorescent probes; heavy metal detection; food safety

Citation: Lai, L.; Yan, F.; Chen, G.;

1. Introduction
Huang, Y.; Huang, L.; Li, D. Recent
Progress on Fluorescent Probes in Metal elements are widely used in our daily lives by virtue of their good thermal and
Heavy Metal Determinations for electrical conductivities, special luster, and excellent ductility. However, with the rapid
Food Safety: A Review. Molecules development of the modern economy, excessive discharge of waste from industry, random
2023, 28, 5689. https://doi.org/ abuse of metal-containing pesticides and fertilizers, and improper handling of common
10.3390/molecules28155689 daily necessities containing metals have led to the massive discharge of heavy metals as
ions into the soil and surface water [1,2]. Heavy metals in the environment can be easily
Academic Editor: Andrea Salvo
accumulated in aquatic products, crops, and other foodstuffs in the form of ions and then
Received: 27 June 2023 be absorbed into the human body through the food chain, which gradually increases the
Revised: 16 July 2023 threat to health via unconscious intaking of heavy metals in our daily lives [3,4].
Accepted: 24 July 2023 Typically, heavy metals are considered as inorganic irritant toxicants and are generally
Published: 27 July 2023 classified into three groups: toxic metals (e.g., mercury, lead, chromium, cadmium, nickel,
arsenic, cobalt, tin), precious metals (e.g., palladium, platinum, silver, gold, plutonium), and
radionuclides (e.g., uranium, thorium, radium, americium) [5]. In particular, mercury, lead,
chromium, and cadmium are present at high levels in the environment and accumulated
Copyright: © 2023 by the authors.
easily in the food chain [6,7]. It has been shown that these heavy metals are prone to
Licensee MDPI, Basel, Switzerland.
react with biomolecular affinity sites and trigger structural changes in biological function
This article is an open access article
molecules in living organisms due to their well-coordinated interactions with biological
distributed under the terms and
conditions of the Creative Commons
function molecules containing nitrogen (N), oxygen (O), and sulfur (S), thus affecting
Attribution (CC BY) license (https://
various cellular enzymes and protein systems inside the body and disrupting their normal
creativecommons.org/licenses/by/ physiological effects [8,9]. For example, mercury (Hg) induces oxidative damage to the
4.0/). mucosa of the gastrointestinal tract and proximal renal tubules, which manifests clinically

Molecules 2023, 28, 5689. https://doi.org/10.3390/molecules28155689 https://www.mdpi.com/journal/molecules

Molecules 2023, 27, x FOR PEER REVIEW 2 of 39

Molecules 2023, 28, 5689 damage to the mucosa of the gastrointestinal tract and proximal renal tubules, which man- 2 of 38
ifests clinically as abdominal pain, hemorrhagic gastroenteritis, acute tubular necrosis,
and subacute shock [10,11]. The pathophysiological toxicity of lead (Pb) is fairly compli-
cated as it involves almost every organ system, with the most severe neurological mani-
as abdominal pain, hemorrhagic gastroenteritis, acute tubular necrosis, and subacute
festations being seizures and coma [12–14]. Cadmium (Cd) can disrupt iron homeostasis
shock [10,11]. The pathophysiological toxicity of lead (Pb) is fairly complicated as it
in humans by inducing hyperactivation of heme oxygenase-1 (HO-1) and disrupting lipid
involves almost every organ system, with the most severe neurological manifestations
metabolism, which ultimately leads to iron apoptosis [15–18]. The epidemiology of infer-
being seizures and coma [12–14]. Cadmium (Cd) can disrupt iron homeostasis in humans
tility has been shown to be related to the impact of exposure to the heavy metals lead and
by inducing hyperactivation of heme oxygenase-1 (HO-1) and disrupting lipid metabolism,
cadmiumwhich [19,20]. Chromium
ultimately leads to(Cr)-induced
iron apoptosis ROS-mediated oxidative stress
[15–18]. The epidemiology of has been dis-
infertility has been
closedshown
to leadtotoberedox imbalance and affect the balance of antioxidant systems
related to the impact of exposure to the heavy metals lead and cadmium [19,20]. in the body
[21]. In conclusion,
Chromium heavy metals
(Cr)-induced can be uptaken
ROS-mediated through
oxidative the
stress respiratory,
has been discloseddigestive,
to leadand
to redox
dermal imbalance and affect the balance of antioxidant systems in the body [21]. through-
tracts, enter the bloodstream, and rapidly distribute to organs and tissues In conclusion,
out the body,metals
heavy whichcan ultimately leadsthrough
be uptaken to neurological disorders,
the respiratory, skin andand
digestive, vascular
dermal damage,
tracts, enter
immune system dysfunction, gastrointestinal and renal dysfunction,
the bloodstream, and rapidly distribute to organs and tissues throughout the body, and even some can-which
cers. Therefore, the development of rapid, sensitive, and specific-response
ultimately leads to neurological disorders, skin and vascular damage, immune qualitative andsystem
quantitative methods
dysfunction, for the detection
gastrointestinal of heavy
and renal metals inand
dysfunction, foodeven
andsome
agriculture-related
cancers. Therefore,
matrices
the is of great importance
development of rapid, for food safety,
sensitive, environmental monitoring,
and specific-response qualitative and and clinical
quantitative
diagnosis.
methods for the detection of heavy metals in food and agriculture-related matrices is of
The
greatdetermination
importance for offood
heavy metals
safety, is facilitated
environmental by applying
monitoring, andnovel
clinicalinstrumental
diagnosis.
methods, such as atomic absorption spectrometry, neutron activation
The determination of heavy metals is facilitated by applying novel instrumentalanalysis, X-ray flu- meth-
orescence spectrometry,
ods, such ion chromatography,
as atomic absorption spectrometry, Raman
neutronspectroscopy, etc., toward
activation analysis, X-raythe de-
fluorescence
tection of metal elements
spectrometry, [22–24]. AmongRaman
ion chromatography, them, fluorescent
spectroscopy, small
etc.,molecule
toward the materials
detection have
of metal
attracted much[22–24].
elements attention because
Among of their
them, short response
fluorescent time, simple
small molecule operation,
materials high se-much
have attracted
lectivity and sensitivity,
attention because ofand greater
their short suitability for the
response time, analysis
simple of tracehigh
operation, metal ions in com-
selectivity and sensi-
plex matrices [25,26] (Scheme 1). Therefore, this review comprehensively
tivity, and greater suitability for the analysis of trace metal ions in complex matrices presents the re-[25,26]
cent research
(Schemeprogress on optical
1). Therefore, techniques
this review for the detection
comprehensively of heavy
presents metal ions
the recent in food
research progress
over the past five
on optical years, especially
techniques in termsofofheavy
for the detection analytical
metalmethods based
ions in food over onthefluorescent
past five years,
materials, attempting
especially to provide
in terms a deeper
of analytical understanding
methods based onoffluorescent
the challenges and future
materials, pro-
attempting to
spectsprovide
of theiraapplications.
deeper understanding of the challenges and future prospects of their applications.

Scheme 1. Fluorescent
Scheme probe-based
1. Fluorescent assaysassays
probe-based for determining heavyheavy
for determining metals in food
metals (e.g.,(e.g.,
in food Cr, Cd,
Cr, Hg,
Cd, Hg, Pb,
Pb, Ag,Ag,
As).
As).

2. Common Fluorescence Spectroscopy Detection Methods

Rapid developments in photochemistry have greatly facilitated the development of
instruments and methods for the convenient and accurate detection of metals, quasi-metals,
and selected non-metallic elements at (super) trace levels since the 1980s [27]. Common spec-
troscopic analytical methods include inductively coupled plasma emission spectrometry
(ICP-MS), atomic fluorescence spectrometry (AFS), atomic absorption spectrometry (AAS),
Molecules 2023, 28, 5689 3 of 38

atomic emission spectrometry (AES), X-ray fluorescence spectrometry (XRF), etc. [22,28].
Further breakthroughs in convenience and sensitivity have been achieved by simplifying
sample pre-treatment, combining different analytical methods in recent years, and opti-
mizing analytical conditions, thereby enabling the monitoring of the spatial distribution of
heavy metals in food entities [29] (Table 1).
ICP-MS has been reported in the literature as the most effective quantitative analyt-
ical method for measuring trace elements in food samples (such as peanuts [30], salted
foods, and sea salt [31]), due to its high sensitivity and selectivity. Additionally, it can be
combined with other technologies for superior detection efficiency. A new method for
the efficient monitoring of the spatial distribution of Hg and Se in mushrooms (with a
spatial resolution as low as 5 µm) was proposed for the first time, with researchers using
laser ablation (LA) and ICP-MS to quantify mercury and selenium in mushroom sub-
strates with detection limits of 0.006 and 0.3 µg·g−1 , respectively [32]. For accomplishing
the simultaneous determination of trace selenium and cadmium in rice samples, G. Lan
et al. [33] first introduced bypass gas to modify graphite furnace electrothermal evapora-
tion (GF-ETV) and ICP-MS. Through optimization, the detection limits of selenium and
cadmium were as low as 0.5 and 0.16 µg·kg−1 respectively, with repeated determinations
exhibiting relative standard deviations (RSDs) within 8% (n = 6). Pre-concentration of
samples to enhance sensitivity is another focus of improvement schemes. Solid phase
extraction (SPE) is the simplest method for pre-concentration. Compared with the classical
liquid–liquid extraction method, SPE presents advantages such as less sample consumption,
higher multiples of accumulation, better recoveries, rapid phase separation, cheaper costs,
etc. Based on these advantages, a method was constructed with flow injection (FI) and
SPE-ICP-MS [34]. It combined chemometric methods with experimental design and multi-
response surface methodology to simultaneously determine toxic elements. The method
successfully reduced the detection limits, ranging from 0.8 ng·L−1 for Mn to 0.09 µg·L−1
for Hg, with relative standard deviations all < 5%, and was successfully applied to the
determination of heavy metals in rice and rice products. Similarly, D. Chen et al. [35]
established a simple and efficient method, which combined high-performance liquid
chromatography–atomic fluorescence spectrometry (HPLC-AFS) and SPE. The method
showed high sorption capacity and a wide range of adaptability for the simultaneous
determination of four forms of mercury (Hg2+ , MeHg, EtHg, PhHg). Under optimized con-
ditions, the limits of detection were 0.001–0.002 µg·L−1 , the recoveries were 87.2–111%, and
the reproducibilities were 1.1–6.5% in water samples. Pre-treatment of complex samples
before detection is another significant scheme to enhance flexibility and sensitivity. For
example, pre-emptive microwave digestion of samples, such as beverages and chocolate,
utilizing 20% nitric acid (v/v) made it possible to decrease the detection limit to parts
per trillion (ng·L−1 ) using an ICP-MS technique [36]. Similarly, when studying sample
pre-treatment methods, such as type, concentrations, and system ratios of ablation reagents,
for the combination of ICP-MS and atomic emission spectrometry (AES), a method for the
simultaneous determination of Ag, As, Bi, Cd, Cr, and other heavy metals in turmeric was
developed [37].
AES, AFS, and AAS are complementary technologies. They have become mainstream
methods for determining heavy metals in agriculture and potable water due to their ad-
vantages of low detection limits, high accuracy, good selectivity, less sample consumption,
and a wide range of applications. They are suitable for the analysis of trace components in
samples such as wheat flour [38], honey [39], and milk powder [40]. Two serially-connected
graphite tubes were innovatively applied as two electrolytic cells to form an electrochemi-
cal vapor generation atomic fluorescence spectrometry (EcHG) system with AES [41]. It
worked well in the determination of trace Cd without ion exchange membranes, with easy
assembly, direct sample detection, and stable signal retention. The limit of detection was
0.05 ng·mL−1 , with a relative standard deviation of 3.2%, and the EcHG efficiency was
38.4 ± 2.2%. Also, it was successfully applied to the determination of potable water samples
with recoveries of 95–109%. Coupling with other technologies facilitates further improve-
Molecules 2023, 28, 5689 4 of 38

ments in detection efficiency. A chemical vapor generation multi-channel non-dispersive

atomic fluorescence spectrometer (CVG-NDAFS) was developed to simultaneously detect
arsenic, antimony, selenium, and mercury in herbal foods and biological standards [42]. The
optimized method reduced the detection limits to 0.051, 0.034, 0.050, and 0.0058 ng·mL−1 ,
respectively, with relative standard deviations of 0.42%, 0.74%, 0.97% and 1.0%, respectively.
Solid injection electrothermal evaporation atomic absorption spectrometry (SS-ETV) was
combined with AAS to determine the cadmium content in chocolate [43]. By optimizing
the experimental conditions, the limit of detection was successfully decreased from 150
to 70 pg·g−1 , accompanied by a high correlation coefficient (R2 > 0.999). Furthermore,
the relative standard deviation of the actual sample detection ranged from 1.5% to 6.4%,
indicating a satisfactory level of precision.
XRF is an analytical technique that utilizes the absorption variations in samples of
X-rays to determine its composition. It offers several advantages, such as rapid analysis,
the ability to analyze a wide range of elements, strong applicability, minimal spectral
interference, and a nondestructive nature towards the sample. This method is not only
capable of analyzing solid block samples but also provides the means to analyze the com-
position and thickness of individual layers within multilayer coatings [44]. The majority of
detection limits can reach up to 10−6 , and when combined with separation and enrichment
techniques, this limit can be further enhanced to 10−8 . Total reflection X-ray fluorescence
analysis (TXRF) was successfully applied in the analysis of heavy metal components in
herbal medicines [45]. Based on high definition X-ray fluorescence spectroscopy (HDXRF),
a method for the rapid quantification of arsenic (As), cadmium (Cd), nickel (Ni), lead (Pb),
tin (Sn), and zinc (Zn) in scallops was developed [46], with detection limits of 0.072, 0.070,
0.502, 0.063, 0.033, and 4.383 mg·kg−1 , respectively. The RSD values of precision, repro-
ducibility, and stability assays were found to be less than 10%. In recent years, portable
instruments have been successfully developed to further broaden the practical applicability
of XRF. G. E. Acquah et al. [47] reported a portable handheld X-ray fluorescence (pXRF)
spectrometer to successfully achieve highly accurate and efficient detection of trace heavy
metal contaminants (chromium, nickel, and arsenic) in fertilizers. Researchers evaluated the
common pXRF method, acid ablation inductively coupled plasma mass spectrometry, and
diphenylcarbonyldihydrazide colorimetric methods for the assessment of lead detection in
69 spices worldwide, which helped to reduce lead exposure [48].
Laser-induced breakdown spectroscopy (LIBS) technology has gradually emerged
in the technical field of heavy metal detection owing to its rapid detection and green ad-
vantages [49]. Q. Zhao et al. [50] brought forth a new idea that constructed a heavy metal
content prediction model using near-infrared (NIR) and LIBS spectral data, with simulta-
neous multi-element detection and prediction accuracy as high as 0.90. The coefficients of
determination in the optimal prediction models for Zn, Cu, and Pb were 0.9858, 0.9811, and
0.9460, respectively, and the root mean square errors of prediction were 4.3047, 4.9592, and
8.3881 mg·kg−1 , respectively, which provided good reproducibility for the rapid detection
of heavy metals in lilies.

Table 1. Common fluorescence spectrometry technologies for the detection of heavy metals in food.

Method Analytes LOD Sample Ref.

ICP-MS As, Pb, Cd, etc. 0.0003–2.47 mg·kg−1 peanuts [30]
HPLC-ICP-MS As 1.12 µg·kg−1 salted foods, sea salt [31]
Hg 0.006 µg·g−1
LA-ICP-MS mushrooms [32]
Se 0.3 µg·g−1
Se 0.5 µg·kg−1
GF-ETV-ICP-MS rice [33]
Cd 0.16 µg·kg−1
FI-SPE-ICP-MS Cd, Hg, Pb, etc. 0.8 ng·L−1 –0.09 µg·L−1 rice [34]
Molecules 2023, 28, 5689 5 of 38

Table 1. Cont.

Method Analytes LOD Sample Ref.

SPE-HPLC-AFS Hg2+ , MeHg, etc. 0.001–0.002 µg·L−1 water [35]
ICP-AES Hg parts-per-trillion (ng·L−1 ) cannabinoid-based products [36]
ICP-MS-AES Ag, As, Pb, etc. below 3 mg·kg turmeric [37]
ICP-AES Cd, As, Cu, etc. 0.008, 0.017, 0.0006, etc. (µg·L−1 ) wheat and flour products [38]
ICP-MS/AAS Mn, Cr, As, etc. 0.1–23.2 mg·kg−1 honey [39]
ICP-AES Hg, As, Cd, etc. 1.80 × 10−5 –2.17 × 10−3 mg·kg−1 milk powder [40]
EcHG-AFS Cd 0.05 ng·mL−1 drinking water [41]
As 0.051 ng·mL−1
Sb 0.034 ng·mL−1
CVG-NDAFS Chinese herbal foods [42]
Se 0.050 ng·mL−1
Hg 0.0058 ng·mL−1
SS-ETV-AAS Cd 70 pg·g−1 chocolate [43]
TXRF Mn, Ni, Rb, etc. 0.25–0.50 mg·kg−1 herbal infusion teas [45]
HDXRF As, Cd, Pb, etc. 0.072, 0.502, 0.063, etc. (mg·kg−1 ) scallops [46]
pXRF Cr, Ni, As 20 mg·kg−1 fertilizers [47]
pXRF-ICP-MS Pb 2 mg·kg−1 spices [48]
NIR-LIBS Zn, Cu, Pb 4.3047, 4.9592, 8.3881 (mg·kg−1 ) lilies [50]

3. Spectroscopic Detection Methods Based on Fluorescent Probes

Although traditional methods can achieve accurate quantitative analysis of trace heavy
metals in food, they often suffer from the disadvantages of complex operation processes,
large amounts of reagents, long analysis times, expensive analytical instruments, and high
requirements for professional and technical personnel [51]. In contrast, fluorescent probes
can emit fluorescence at certain wavelengths when irradiated by ultraviolet light or visible
light, with excellent photophysical properties such as high extinction coefficients, excellent
quantum yields, and relatively long emission wavelengths. The characteristics of fluores-
cent probes can be changed with the environment so as to achieve effective detection of the
measured substances with the advantages of good sensitivity, high selectivity, and short
response times [52]. In recent years, fluorescent probe-based detection methods for heavy
metals have been widely investigated by researchers. The focus of these methods has been
the design and synthesis of specific probes with appropriate fluorophores and exploring
the potential specific mechanisms. Herein, examples are summarized and classified, such
as rhodamine, Schiff base, quinoline, coumarin, azoles, thiourea, tetraphenylene (TPE),
thiophene, naphthoimide, etc.

3.1. Rhodamine-Based Fluorescent Probes

Rhodamine spirolactam or spirolactone derivatives are non-fluorescent and colorless,
while the ring opening of the corresponding spirolactam/lactone produces strong fluores-
cence emission and color change, which is an excellent characteristic for the preparation of
fluorescence-enhanced probes (Scheme 2a). It is the most researched class of fluorescent
probes by far (Figure 1). R1 was designed as a selective probe for Pb2+ upon the combina-
tion of 2,6-diformyl-4-methylphenol with rhodamine 6G as the backbone [53]. The color of
the working solution changes from light yellow to pink after recognition of Pb2+ , which
can achieve visual determination of Pb2+ . The limit of detection is 2.7 × 10−9 M, and R1
has been applied to detect lead in seafood, such as clams and scallops, with recoveries of
91.3–93.5%. Similarly, REHBA is a colorimetric fluorescent probe based on rhodaminohy-
drazine and 2,3,4-trihydroxybenzaldehyde that can effectively detect Pb2+ [54]. Its limit
of detection is as low as 0.73 µM. It has been successfully applied in real water samples.
 the combination of 2,6-diformyl-4-methylphenol with rhodamine 6G as the backbone [53].
The color of the working solution changes from light yellow to pink after recognition of
Pb2+, which can achieve visual determination of Pb2+. The limit of detection is 2.7 × 10−9 M,
and R1 has been applied to detect lead in seafood, such as clams and scallops, with
recoveries of 91.3–93.5%. Similarly, REHBA is a colorimetric fluorescent probe based on
Molecules 2023, 28, 5689 rhodaminohydrazine and 2,3,4-trihydroxybenzaldehyde that can effectively detect6 Pb of 38
2+

[54]. Its limit of detection is as low as 0.73 µM. It has been successfully applied in real
water samples. A. Roy et al. [55] synthesized two novel rhodamine-based compounds.
A.
OneRoy
(3) et al. [55] synthesized
combined two novel rhodamine-based compounds.
5-diethylamino-2-hydroxy-benzaldehyde to detect HgOne (3)other
2+. The combined
(HL-
5-diethylamino-2-hydroxy-benzaldehyde to detect 2+
Hg .Cr The. Their
other detection
(HL-CHO) combined
CHO) combined 2,6-diformyl-4-methyl-phenol to detect 3+ limits are as
2,6-diformyl-4-methyl-phenol
low as 15.80 nM. to detect Cr3+ . Their detection limits are as low as 15.80 nM.

Molecules 2023, 27, x FOR PEER REVIEW 7 of 39

Scheme 2. Recognition
Scheme 2. Recognition mechanisms
mechanisms of of fluorophores:
fluorophores: (a)
(a) rhodamine,
rhodamine, (b)
(b) Schiff
Schiff base,
base, (c)
(c) quinoline,
quinoline,
(d) coumarin, (e) azoles, (f) thiourea, (g) TPE, (h) thiophene, and (i) naphthoimide.
(d) coumarin, (e) azoles, (f) thiourea, (g) TPE, (h) thiophene, and (i) naphthoimide.

Figure 1.
Figure 1. The
The structures of probes
structures of probes ((a–d)
((a–d) are
are R1,
R1, REHBA,
REHBA, 33 and
and HL-CHO,
HL-CHO, respectively).
respectively).

The
The current
current research
research on
on utilizing
utilizing rhodamine-based
rhodamine-based probes
probes for
for heavy
heavy metal
metal detection
detection
in foodprimarily
in food primarilyrevolves
revolvesaround
around modifying
modifying various
various ligands
ligands on spirolactam
on the the spirolactam
ring. ring.
This
modification induces distinct fluorescence or color changes in the probes upon the addi-
tion of different metal ions, thereby facilitating the identification of heavy metals in food.
Additionally, researchers have been focusing on developing portable detection devices
that are practical and applicable in real-world scenarios, alongside the discovery of new
Molecules 2023, 28, 5689 7 of 38

This modification induces distinct fluorescence or color changes in the probes upon the
addition of different metal ions, thereby facilitating the identification of heavy metals
in food. Additionally, researchers have been focusing on developing portable detection
devices that are practical and applicable in real-world scenarios, alongside the discovery of
new probes.

3.1.1. Fluorescent Probes to Detect Hg2+

As shown in Figure 2, a novel ratiometric fluorescent probe for detecting Hg2+ , p-RPT,
was designed with rhodamine derivatives and triphenylamine [56]. The probe could induce
a visible color change (from blue to pink) when identifying Hg2+ in the THF/H2 O (3:2,
v/v) system and performed well in detecting mercury in water samples. Moreover, to ac-
commodate field applications, researchers have developed hydrogel-coated paper sensors
and flexible fluorescent gloves, respectively. The test paper is not only highly sensitive
(the limit of detection is 1.2 × 10−8 M) but also can be stored for a long time. The flexible
fluorescent gloves feature the same advantages, plus strong abrasion resistance. These two
novel fluorescence-sensing tools were both successfully applied in the detection of Hg2+ in
seafood, which provides a new perspective for a wearable sensing apparatus. D114 and
FO511 are two other new rhodamine-lactam probes proposed for Hg2+ detection [57,58].
D114 works well in the MeOH/H2 O (1:1, v/v) system, with a limit of detection of 8.6 nM,
and it could be contained with latex-coated slides for higher sensitivity (limit of detection as
low as 0.5 nM). FO511 is a fluorescein-2-(pyridin-2-ylmethoxy)-benzaldehyde conjugate. It
can generate a 1:1 FO511-Hg2+ complex with a binding constant of (3.21 ± 0.05) × 104 M−1
in HEPES (10 mM, pH = 7.2), which efficiently triggers Hg2+ with a limit of detection
of 92.7 nM. As we all know, NIR fluorescent probes, emitting in the wavelength range
of 650–900 nm, have the advantages of low energy, low background interference, high
tissue penetration, and good imaging effect, and they have been a major hot topic of re-
search in recent years. However, most rhodamine derivatives work in the 400–650 nm
wavelength, restricting their application prospects. Therefore, RBLY was synthesized as
a new NIR rhodamine-based probe to recognize Hg2+ , which turns on strong fluores-
cence upon sensing Hg2+ in the EtOH/H2 O (1:5, v/v) system, with a limit of detection of
0.34 µM [59]. It was successfully applied to water sample detection and live cell imaging.

3.1.2. Fluorescent Probes to Detect Pb2+

For the efficient and convenient detection of Pb2+ in food, R6GH was synthesized
and developed as an immobilized paper-based array sensor [60]. The sensor shows a
good linear relationship response (R2 = 0.9851) in the concentration range of 0.05–6.0 µM,
with a limit of detection of 0.02 µM. It has been successfully applied to aquatic detection
with recoveries in the range of 84.0–102.0% and shows good linearity with the results of
ICP-MS (R2 = 0.9915), which demonstrates it has strong practical applications. In recent
years, fluorescence resonance energy transfer (FRET) techniques based on the principle
of large emission wavelength shifts have shown broad applicability for improved heavy
metal detection in food [61]. In particular, large emission wavelength shifts could avoid
or minimize background interferences, resulting in high signal-to-noise ratios and high
sensitivities with great potential. NA-RhB was presented as a novel sensor using the FRET
principle, with 1,8-naphthalimide as the donor and rhodamine-B as the acceptor, and the
peak wavelength was shifted to the shorter wavelength side (blue shift) with increasing
concentrations of Pb2+ [62]. By observing the variations in emission peak wavelength
shift (from 630.27 nm), a sensing probe for the detection of Pb2+ was developed, with a
detection limit of 0.00001 g·L−1 . FP, another a multifunctional colorimetric sensor based
on rhodamine architecture, is capable of simultaneously sensing Pb2+ and Cd2+ with 2-(2-
((2-hydroxyphenyl)imino)ethylidene) amino and tert-butyldiphenylsilyl modifications [63].
The color of the solution of FP in the EtOH/H2 O (99:1, v/v) system turns light purple by
visual observation after adding Pb2+ or Cd2+ . Especially, when only F− is present, the
color of the FP-Pb2+ solution fades while that of the FP-Cd2+ solution darkens to purple,
Molecules 2023, 28, 5689 8 of 38

Molecules 2023, 27, x FOR PEER REVIEW 8 of 39

which displays the different spectral properties of the probe. The detection limits of FP
are 0.42 µM for Pb2+ and 0.53 µM for Cd2+ , and it has been successfully utilized for the
upon sensing Hg
determination
2+ in the EtOH/H2O (1:5, v/v) system, with a limit of detection of 0.34 µM
of tap water with favorable linear recoveries. The specific structures of the
[59]. It was
probes successfully
are shown applied
in Figure 3. to water sample detection and live cell imaging.

Figure
Figure2.
2.The
Thestructures
structuresof
ofprobes
probes ((a–d)
((a–d) are
are p-RPT,
p-RPT, d114,
d114, FO
FO511 , and RBLY, respectively).
511 , and RBLY, respectively).

3.1.3.Fluorescent
3.1.2. FluorescentProbes
Probes toto Detect
Detect PbCr2+3+
Figure
For 4 illustrates
the efficient RhBQ, a chemosensor
and convenient detection of Pbmodified
2+ in food, with
R6GH2-hydroxyquinoline-3-
was synthesized and
carbaldehyde, which exhibits both fluorescence
developed as an immobilized paper-based array sensor [60]. Theemission and colorimetric sensitivity
sensor shows a goodto-
wards trivalent Cr 3+ in ACN/H2 O (9:1, v/v) medium [64]. The chemosensor has a detection
linear relationship response (R 2= 0.9851) in the concentration range of 0.05–6.0 µM, with
alimit
limitofof2.12 × 10−8of
detection M0.02
andµM.
has been
It hassuccessfully prepared
been successfully as an assay
applied test paper
to aquatic for conve-
detection with
nient usage.
recoveries A novel
in the rangefluorescent probe,
of 84.0–102.0% RFC,
and wasgood
shows synthesized
linearitybywith
combining rhodamine
the results of ICP-
and(R
MS chromone
2 = 0.9915),through
which carbon–nitrogen
demonstrates it has conjugation for the purpose
strong practical of detecting
applications. In recentCr3+ [65].
years,
The fluorescent probe is effective in the MeOH/H O (99:1, v/v) system
fluorescence resonance energy transfer (FRET) techniques based on the principle of large
2 and has a detection
limit of 0.0052
emission ppm. shifts
wavelength Additionally,
have shown thebroad
probeapplicability
exhibited remarkable
for improved anti-cancer
heavy metalactivity
de-
against MCF-7 (breast cancer) cells with
tection in food [61]. In particular, large emission an IC value of 2.53 µM.
50 wavelength shifts could avoid or mini-
mize background interferences, resulting in high signal-to-noise ratios and high sensitiv-
ities with great potential. NA-RhB was presented as a novel sensor using the FRET prin-
ciple, with 1,8-naphthalimide as the donor and rhodamine-B as the acceptor, and the peak
wavelength was shifted to the shorter wavelength side (blue shift) with increasing con-
centrations of Pb2+ [62]. By observing the variations in emission peak wavelength shift
 color of the solution of FP in the EtOH/H2O (99:1, v/v) system turns light purple by visual
observation after adding Pb2+ or Cd2+. Especially, when only F- is present, the color of the
FP-Pb2+ solution fades while that of the FP-Cd2+ solution darkens to purple, which displays
the different spectral properties of the probe. The detection limits of FP are 0.42 µM for
Pb2+ and 0.53 µM for Cd2+, and it has been successfully utilized for the determination of
Molecules 2023, 28, 5689 9 of 38
tap water with favorable linear recoveries. The specific structures of the probes are shown
in Figure 3.

Molecules 2023, 27, x FOR PEER REVIEW 10 of 39

Figure 3.
Figure 3. The
The structures
structures of
of probes
probes ((a)
((a) is
is R6GH,
R6GH, (b)
(b) isisNA-RhB,
NA-RhB, (c)
(c)isisFP).
FP).

3.1.3. Fluorescent Probes to Detect Cr3+

Figure 4 illustrates RhBQ, a chemosensor modified with 2-hydroxyquinoline-3-
carbaldehyde, which exhibits both fluorescence emission and colorimetric sensitivity to-
wards trivalent Cr3+ in ACN/H2O (9:1, v/v) medium [64]. The chemosensor has a detection
limit of 2.12 × 10−8 M and has been successfully prepared as an assay test paper for con-
venient usage. A novel fluorescent probe, RFC, was synthesized by combining rhodamine
and chromone through carbon–nitrogen conjugation for the purpose of detecting Cr3+ [65].
The fluorescent probe is effective in the MeOH/H2O (99:1, v/v) system and has a detection
limit of 0.0052 ppm. Additionally, the probe exhibited remarkable anti-cancer activity
against MCF-7 (breast cancer) cells with an IC50 value of 2.53 µM.

Figure 4.
Figure 4. The structures
structures of
of probes
probes ((a)
((a) is
is RhBQ
RhBQ and
and (b)
(b) is
is RFC).
RFC).

3.2.
3.2. Schiff
Schiff Base-Based
Base-Based Fluorescent
Fluorescent Probes
Probes
Schiff
Schiff bases
bases are
are organic
organic compounds
compounds that that contain
contain imine
imine oror methylimine
methylimine groups
groups (C=N)
(C=N)
with lone pairs of electrons in the hybrid orbitals of nitrogen atoms (Scheme
with lone pairs of electrons in the hybrid orbitals of nitrogen atoms (Scheme 2b). These 2b). These
compounds
compounds are are considered
considered favorable
favorable ligands
ligands and
and exhibit
exhibit photochromic
photochromic characteristics.
characteristics.
Therefore, there is significant interest in developing them as fluorescent
Therefore, there is significant interest in developing them as fluorescent probes forfor
probes detecting
detect-
heavy
ing heavy metals. As shown in Figure 5, a novel photochromic diarylethene containing aa
metals. As shown in Figure 5, a novel photochromic diarylethene containing
quinoline-linked
quinoline-linked 3-aminocoumarin
3-aminocoumarin Schiff
Schiff base
base unit
unit (1 O) was
(1 O) was proposed
proposed [66].
[66]. The
The probe
probe
specifically responds to Cd 2+ in the ACN system, which exhibits a visible color change
specifically responds to Cd in the ACN system, which exhibits a visible color change
2+
(from dark cyan to golden yellow). Receptor is a Schiff base with structural modification of
(from dark cyan to golden yellow). Receptor is a Schiff base with structural modification
a naphthalene base, which is capable of detecting Cr3+3+in aqueous solution, with a limit
of a naphthalene base, which is capable of detecting Cr in aqueous solution, with a limit
of detection of 3.92 µM [67]. It has performed successfully in cell imaging of zebrafish.
of detection of 3.92 µM [67]. It has performed successfully in cell imaging of zebrafish.
Similarly, another probe, C6, was developed from 2,20 -(1E,10 E)-(hexane-1,6-diylbis-(azan-
Similarly, another probe, C6, was developed from 2,2′-(1E,1′E)-(hexane-1,6-diylbis-(azan-
1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)diphenol [68]. This probe exhibited excellent
performance in tap water detection for Cr3+, with a limit detection of 13.3 µM.
 Therefore, there is significant interest in developing them as fluorescent probes for detect-
ing heavy metals. As shown in Figure 5, a novel photochromic diarylethene containing a
quinoline-linked 3-aminocoumarin Schiff base unit (1 O) was proposed [66]. The probe
specifically responds to Cd2+ in the ACN system, which exhibits a visible color change
(from dark cyan to golden yellow). Receptor is a Schiff base with structural modification
Molecules 2023, 28, 5689
of a naphthalene base, which is capable of detecting Cr3+ in aqueous solution, with a10limit
of 38

of detection of 3.92 µM [67]. It has performed successfully in cell imaging of zebrafish.

Similarly, another probe, C6, was developed from 2,2′-(1E,1′E)-(hexane-1,6-diylbis-(azan-
1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)diphenol [68].
1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)diphenol [68]. This
This probe
probe exhibited
exhibited excellent
3+ with a limit detection of 13.3 µM.
performance in tap water detection for Cr3+,,with a limit detection of 13.3 µM.

Figure 5. The structures of probes ((a) is 1 O, (b) is Receptor, (c) is C6).

Despite the development of numerous fluorescent probes based on the Schiff base
framework, their practical applications are relatively rare due to their instability, weak
specificity, and susceptibility to interference. However, in recent years, Schiff base structure-
based fluorescent probes have overcome these limitations and have been successfully
utilized for the detection of Cr3+ , Cd2+ , Pb2+ , and so on.

3.2.1. Fluorescent Probes to Detect Cr3+

As shown in Figure 6, PBD is a novel probe derived from pyrene, which exhibits
strong fluorescence turn-on towards Cr3+ and fluorescence turn-off towards Hg2+ in the
EtOH/H2 O (1:1, v/v) system [69]. This unique sensitivity enables simultaneous detection
of Cr3+ and Hg2+ , with detection limits of 0.32 and 1.93 µM, respectively. The authors also
tested the probe on tap water and soil, achieving favorable recoveries ranging from 96.0% to
105.7%. From 5-(thiophen-2-yl)oxazole-4-carbohydrazide and 4-diethylaminosalicylaldehyde, P
was synthesized [70]. The sensor selectively quenches green fluorescence when determining
Cr3+ in the DMF/H2 O (9:1, v/v) system, with a limit of detection of 9.82 × 10−9 M. This
sensor has been successfully utilized for monitoring targeted ions in actual water samples.
A novel thiazole-based fluorescent and colorimetric Schiff base chemosensor, SB2, was
designed to achieve highly sensitive, selective, and efficient identification [71]. It operates
in the MeOH/H2 O (3:1, v/v) system and exhibits fluorescence turn-on and a colorimetric
response (from yellow to colorless), with detection limits as low as 0.5 µM. In addition, SB2
has been successfully applied in soil samples with recoveries ranging from 95.00 ± 0.50% to
99.00 ± 0.14%. The dicyanomethylene-4H-pyran (DCM) unit is one of the most commonly
used NIR fluorophores, with a large Stokes shift and high light stability [72]. Therefore,
HMA was designed containing DCM [73]. The process of determining Cr3+ along with the
NIR fluorescence enhancement in the DMSO/H2 O (9:1, v/v) system yielded a detection
Molecules 2023, 28, 5689 11 of 38

limit of 5.63 × 10−7 M. This probe has been successfully applied to the detection of water
samples. A thiophene-substituted naphthyl hydrazone derivative, NHT, was synthesized
using a one-step route for the detection of trivalent Cr3+ [74]. It shuts off fluorescence
in HEPES buffer (0.2 M, pH = 7.2), with a limit of detection of 41 nM. The modification
enhances probe solubility and biocompatibility, which allowed its further application in
the bioimaging of PC3 cells (human prostate cancer cells). R. Chandra et al. [75] designed
and synthesized two salicylaldimine-functionalized dipodal bis Schiff base fluorescent
colorimetric chemosensors, L1 (4-(2-hydroxy-3-methoxybenzyl-ideneamino)phenyl) and
L2 (4-phenylimino)4-diethylsalicyl-al-dehyde). They were able to distinguish Cr3+ in the
ACN/H2 O (1:1, v/v) system. L1 shows a binding constant of 1.26 × 105 M−1 with a
detection limit of 1.12 × 10−7 M, while L2 shows a binding constant of 3.0 × 105 M−1
Molecules 2023, 27, x FOR PEER REVIEW
with a detection limit of 7.73 × 10−7 M. Researchers also successfully developed12aofvisible
39

colorimetric kit and applied it to rapid detection in real water samples.

Figure 6.
Figure 6. The structures
structures of
of probes
probes((a–g)are
((a–g)arePBD,
PBD,P,P,SB2,
SB2,HMA,
HMA,NHT,
NHT,L1,L1,
and L2,L2,
and respectively).
respectively).

3.2.2. Fluorescent Probes to Detect Cd3+

In Figure 7, PIS was developed as a novel ratiometric phenazine-imidazole-Schiff
base fluorescent probe [76]. The probe works in the ACN/HEPES buffer (10 mM, pH = 7.4)
(1:4, v/v) system. It evokes a significant fluorescence color change (from yellow to orange-
Molecules 2023, 28, 5689 12 of 38

3.2.2. Fluorescent Probes to Detect Cd3+

In Figure 7, PIS was developed as a novel ratiometric phenazine-imidazole-Schiff base
fluorescent probe [76]. The probe works in the ACN/HEPES buffer (10 mM,
pH = 7.4) (1:4, v/v) system. It evokes a significant fluorescence color change (from yellow
to orange-red), followed by a large red shift of the Stokes peak (542 to 608 nm). Through
monitoring the variation in the fluorescence ratio at 608 and 542 nm with increasing Cd2+
concentration at Ex.406 nm, this probe can detect Cd2+ with detection limits as low as
2.10 × 10−8 M. In addition, this probe has been successfully applied to cell imaging of
zebrafish larvae and Chinese rice locust cells with specific potential. Z. Wang et al. [77]
reported a different Schiff base fluorescent probe modified with diaryl ethylene derivatives
Molecules 2023, 27, x FOR PEER REVIEW 13 of 39
2+
(1 O). The probe detects Cd in THF medium, evoking photochromism (fluorescence
color changed from black to green) and a fluorescence turn-on effect, accompanied by a
significant red shift
the fluorescence of the peak
emission fluorescence emission
(up to 105 nm). Thepeak (up has
sensor to 105 nm). The
a binding sensorofhas
constant 4.36a
binding constant of 4.36 × 10 4 M−1 and a detection limit of 5.74 × 10−7 M. It has been
× 104 M−1 and a detection limit of 5.74 × 10−7 M. It has been successfully utilized for accurate
successfully
detection in utilized forsamples.
tap water accuratePMPA
detection
wasindesigned
tap waterand
samples. PMPAas
synthesized was designed
a probe and
custom-
synthesized as a probe customized by pyridine derivatives with the photoinduced electron
ized by pyridine derivatives with the photoinduced electron transfer (PET) mechanism
transfer (PET) mechanism and chelation-enhanced fluorescence (CHEF) properties for the
and chelation-enhanced fluorescence (CHEF) properties for the selective detection of Cd2+
selective detection of Cd2+ in ACN [78]. The probe exhibits a wide pH range flexibility
in ACN [78]. The probe exhibits a wide pH range flexibility (5–9), quick response time (3
(5–9), quick response time (3 min), excellent sensitivity (LOD = 0.12 mM), and favorable
min), excellent sensitivity (LOD = 0.12 mM), and favorable reversibility. Furthermore, it
reversibility. Furthermore, it has been successfully applied to determine real water samples.
has been successfully applied to determine real water samples.

probes ((a)
Figure 7. The structures of probes ((a) is
is PIS,
PIS, (b)
(b) is
is 11 O,
O, (c)
(c) is
is PMPA).
PMPA).

3.2.3. 2+
3.2.3. Fluorescent
Fluorescent Probes
Probes to
to Detect
Detect Pb
Pb2+
DBTBH is
DBTBH is aaSchiff
Schiffbase
basefluorescent
fluorescent probe
probeamended
amended with a benzenesulfonylhydrazone
with a benzenesulfonylhydra-
derivative 2+
zone derivative [79]. The probe exhibits rapid, efficient, and sensitiveresponse
[79]. The probe exhibits rapid, efficient, and sensitive responsetotoPb Pb2+ in
in
THF/Tris-HCl
THF/Tris-HCl buffer(10
buffer (10mM,
mM,1 1mM mM KI,KI,
pHpH = = 7.4)
7.4) (1:9,
(1:9, v/v),v/v),
with with
a a detection
detection limit limit
of 4.49of×
−8
10−8 ×
4.49 M.10TheM. The recognition
recognition process process exhibits
exhibits excellent
excellent optical
optical properties
properties of aggregation-
of aggregation-in-
induced emission enhancement (AIEE) and intramolecular charge transfer
duced emission enhancement (AIEE) and intramolecular charge transfer (ICT). It (ICT). It has
has been
been
implemented in real water samples. Another novel symmetric tridentate
implemented in real water samples. Another novel symmetric tridentate probe, BSBBT, probe, BSBBT,
facilely equipped with a benzodiazole and salicylaldehyde structure, is able to detect Pb2+
in the DMSO/H2O (3:7, v/v) system with a detection limit of 2.23 × 10−6 M [80]. The photo-
physical analysis showed an enhanced emission in the aggregates with excellent AIEE
properties in solution or solid state. The tautomerization of keto/enol or hydrogen bond-
Molecules 2023, 28, 5689 13 of 38

facilely equipped with a benzodiazole and salicylaldehyde structure, is able to detect Pb2+
in the DMSO/H2 O (3:7, v/v) system with a detection limit of 2.23 × 10−6 M [80]. The
photophysical analysis showed an enhanced emission in the aggregates with excellent AIEE
properties in solution or solid state. The tautomerization of keto/enol or hydrogen bonding
interactions in the molecule are the origin of the large Stokes shifts and d excited-state
intramolecular proton transfer (ESIPT) properties, which enable it to be a useful material
for photonic devices. L, a Schiff base modified with triazole derivatives, was proposed as a
new colorimetric chemosensor [81]. The imine-attached triazole moiety contains multiple
pockets suitable for metal coordination, whereas the phenol containing two methoxy groups
Molecules 2023, 27, x FOR PEER REVIEW 14 of 39
acts as a signaling sub-unit, which enhances the ICT and PET processes. It recognizes Pb2+
in the MeOH/Tris buffer (1:1, v/v) system, with sensible colorimetric sensing capability
(from colorless to light yellow), strong fluorescence turn-on, and a detection limit of
9 × 10
limit of−97 ×M.
10This
−7 M.sensor has been
This sensor hassuccessfully employed
been successfully in real water
employed in realsamples. The specific
water samples. The
structures
specific of the probes
structures of the are shown
probes are in Figure
shown in8.Figure 8.

Figure
Figure8.
8.The
Thestructures
structuresof
ofprobes
probes ((a)
((a) is
is DBTBH,
DBTBH, (b)
(b) is
is BSBBT,
BSBBT, (c)
(c) is
is L).
L).

3.3.Quinoline-Based
3.3. Quinoline-BasedFluorescent
FluorescentProbes
Probes
Quinolineand
Quinoline andits
itsderivatives
derivativesare
arecommon
commonmetal
metalion
ionchelators,
chelators,with
withrigid
rigidstructures,
structures,
large conjugation complexes, and excellent performance in aqueous solvents. Normally,
large conjugation complexes, and excellent performance in aqueous solvents. Normally,
the fluorescence is enhanced after complexing with metal ions, so quinolines have often
the fluorescence is enhanced after complexing with metal ions, so quinolines have often
been employed in the development of fluorescent probes in recent years (Scheme 2c).
been employed in the development of fluorescent probes in recent years (Scheme 2c).
3.3.1. Fluorescent Probes to Detect Cd3+
3.3.1. Fluorescent Probes to Detect Cd3+
As shown in Figure 9, probe 1 was synthesized as a novel ratiometric fluorescent
As shown in Figure 9, probe 1 was synthesized as a novel ratiometric fluorescent
probe via combining the fluorescent group of 8-aminoquinoline with an amide group on
probe via combining the fluorescent group of 8-aminoquinoline with an amide group on
the chelating site of propargylamine [82]. The probe can detect Cd2+ in ACN through ob-
servation of the variation in the fluorescence ratio response between 500 and 405 nm under
Ex.335 nm with increasing Cd2+ concentration and has a detection limit of 0.055 µM. In
addition, the researchers explored probe 1 as test strips, which have been successfully
Molecules 2023, 28, 5689 14 of 38

the chelating site of propargylamine [82]. The probe can detect Cd2+ in ACN through
observation of the variation in the fluorescence ratio response between 500 and 405 nm
under Ex.335 nm with increasing Cd2+ concentration and has a detection limit of 0.055 µM.
In addition, the researchers explored probe 1 as test strips, which have been successfully
applied in water samples, bean sprouts, etc. QTPY was reported as a ratiometric fluorescent
probe, 40 -quinolin-2-yl-[2, 20 ; 60 , 200 ] terpyridine [83]. The probe is capable of detecting Cd2+
in the DMF/H2 O (4:6, v/v) system based on the intramolecular electron transfer mechanism.
The fluorescence intensity increases significantly with increasing Cd2+ concentration at
520 nm and shows a favorable linear relationship with a detection limit of 3.5 × 10−8 M. By
Molecules 2023, 27, x FOR PEER REVIEW 15 of 39
combining 2-hydroxy-1-naphthaldehyde and 2-hydrazinoquinoline, L was developed [84].
The free L shows no fluorescence due to the companied PET and C-N isomerization
mechanism, while when it is coordinated with Cd2+ in the ACN/H2 O (8:2, v/v) system,
free ligand
system, freeC-N isomerization
ligand is restricted
C-N isomerization and the CHEF
is restricted phenomenon
and the induces enhanced
CHEF phenomenon induces
fluorescence. It also evokes
enhanced fluorescence. It alsoaevokes
variation in colorinfrom
a variation colorcolorless to crimson
from colorless yellow.
to crimson The
yellow.
probe forms a 2:1acomplex Cd2+Cd
withwith with a binding constant of 1.77 5 M
× ×1010 −−1
1 and a
The probe forms 2:1 complex 2+ with a binding constant of 1.77 5 M and
detection limit of 14.8 14.8 nM.
nM. ItIt performed
performed well well inin detection
detection ofof different
different water
water samples.
samples. A
newly designed and synthesized quinoline-based chemosensor, DDTQ, was reported for
the detection of
the detection Cd2+2+ininaqueous
of Cd aqueous media
media [85].
[85]. It shows
It shows excellent
excellent luminescence
luminescence behavior
behavior fol-
following the PET and CHEF mechanisms, which yields significantly
lowing the PET and CHEF mechanisms, which yields significantly enhanced fluorescence enhanced fluorescence
at
at 445
445 nm,
nm, with
with aa detection
detection limit
limit of
of 126
126 nM.
nM. Furthermore,
Furthermore, the the probe
probe performs
performs withwith low
low
toxicity
toxicity and excellent biocompatibility, which motivated the researchers to explore the
and excellent biocompatibility, which motivated the researchers to explore the
biofluorescence
biofluorescence imaging
imaging applications
applications inin living
living cells,
cells, as
as well
well as
as illustrating
illustrating the
the potential
potential forfor
its real-life applications.
its real-life applications.

probes ((a–d)are
Figure 9. The structures of probes ((a–d)are probe
probe 1,
1, QTPY,
QTPY, LL and
and DDTQ,
DDTQ, respectively).
respectively).

3.3.2. 2+ and Hg2+

3.3.2. Fluorescent
Fluorescent Probes
Probes to
to Detect
Detect Pb
Pb2+ and Hg2+
A novel fluorescent
A novel fluorescent probe,
probe,Pb(II)-IIP, wascreated
Pb(II)-IIP,was createdbyby modifying
modifying a 5-amino-8-
a 5-amino-8-hy-
hydroxyquinoline-type probe with styryl anthracene derivatives. The
droxyquinoline-type probe with styryl anthracene derivatives. The probe was then probe was man-
then
manufactured into microbeads through polymerization with ethylene glycol
ufactured into microbeads through polymerization with ethylene glycol dimethacrylate dimethacry-
late (EGDMA) 2+ in pure
(EGDMA) [86].[86]. The highly
The highly mesoporous
mesoporous material
material is capable
is capable of detecting
of detecting Pb− 2+ inPbpure water,
1 . The method
water, hence turning on the fluorescence with a detection limit of 2.1 µg · L
hence turning on the fluorescence with a detection limit of 2.1 µg·L . The method has been
−1

successfully applied in tap water, mineral water, and seawater sample determination. An-
other novel quinoline-morpholine conjugate, QMC, was also developed [87]. The probe
displays highly selective detection of Pb2+ in the ACN/H2O (1:1, v/v) system, exhibiting a
large blue shift and fluorescence enhancement during the assay. It is the first fluorescent
Molecules 2023, 28, 5689 15 of 38

has been successfully applied in tap water, mineral water, and seawater sample determi-
nation. Another novel quinoline-morpholine conjugate, QMC, was also developed [87].
The probe displays highly selective detection of Pb2+ in the ACN/H2 O (1:1, v/v) system,
exhibiting a large blue shift and fluorescence enhancement during the assay. It is the first
fluorescent chemosensor to employ blue shift tuning via the ICT process for the detection
of Pb2+ . Furthermore, QMC exhibited no interference among alkali metal, alkaline earth
metal, and transition metal ions, with a detection limit of 13 µM. The researchers have also
extended the usage of the probe for the detection of Pb2+ in milk and red wine, with a recov-
ery between 93.7%–103.2%. S. Che et al. [88] presented a novel ionic fluorescent probe, IL
Molecules 2023, 27, x FOR PEER REVIEW 16 of 39
[HDQ] [P66614], consisting of a functional quinoline-based compound. It works in ethanol
2+
solution for Hg detection. Interestingly, the probe exhibits two different fluorescence
signals in the presence of various concentrations of Hg2+ . The fluorescence intensity first
graduallyincreases
gradually increaseswhen
whenthe Hg2+
theHg 2+ concentration
concentration is is increased
increasedfromfrom11toto300
300nM,
nM,accompa-
accom-
nied by
panied bya ablue shift
blue of of
shift thethe
emission
emission peak
peakfrom 413413
from to 388 nm, nm,
to 388 while the fluorescence
while inten-
the fluorescence
intensity gradually
sity gradually decreases
decreases withwith the peak
the peak continuing
continuing to blue
to blue shift shift
fromfrom 300
300 to tonm
103 103when
nm
when the2+Hg 2+ concentration continues to accumulate. The researchers hypothesized and
the Hg concentration continues to accumulate. The researchers hypothesized and con-
confirmed
firmed this this
waswas
duedue to two
to two interaction
interaction modes:modes: electrostatic
electrostatic attraction
attraction and chemical
and chemical conju-
conjugation.
gation. First,First, the probe
the probe mainlymainly
engages engages in electrostatic
in electrostatic attraction
attraction to formtoa large
form complex
a large
complex
regime in regime in the presence
the presence of a tinyofamount
a tiny amount
of Hg2+ of Hg2+
while while
the the phototransfer
phototransfer effect of effect of
the func-
the functional group (the [HDQ] [P66614] part) is hindered. Then,
tional group (the [HDQ] [P66614] part) is hindered. Then, the probe engages in chemical the probe engages in
chemical conjugation with additional 2+ , the original complex regime is disrupted, and
conjugation with additional Hg2+, theHg original complex regime is disrupted, and new qua-
new quaternary
ternary anion complexes
anion complexes appear.appear. Therefore,
Therefore, the probe
the probe is useful
is useful as a fluorescent
as a fluorescent col-
colorimet-
orimetric 2+ within a concentration range of 1–10 3
ric probeprobe for real-time
for real-time monitoring
monitoring of 2+Hg
of Hg within a concentration range of 1–103 nMnM and
and the detection limit is 0.8 nM. It has been successfully employed in real
the detection limit is 0.8 nM. It has been successfully employed in real water samples, fish, water samples,
fish,
andand shrimp.
shrimp. TestTest strips
strips basedbased
on ILon[HDQ]
IL [HDQ] havehave
[P66614]
[P66614] been been developed
developed to further
to further enrich
enrich its application prospects in various industries. The specific
its application prospects in various industries. The specific structures of the probesstructures of the probesare
are shown
shown in in Figure
Figure 10.10.

Figure10.
Figure 10.The
Thestructures
structuresofofprobes
probes((a)
((a)is isPb(II)-IIP,
Pb(II)-IIP, (b)
(b) is is QMC,
QMC, (c)(c)
is is
ILIL [HDQ]
[HDQ] [P66614]).
[P66614]).

3.4. Coumarin-Based Fluorescent Probes

The coumarin parent is not fluorescent, while the derivatives of coumarin show in-
tense fluorescence, containing a push–pull electron system formed through the incorpo-
ration of different electron-absorbing and electron-donating groups. The derivatives pos-
Molecules 2023, 28, 5689 16 of 38

3.4. Coumarin-Based Fluorescent Probes

The coumarin parent is not fluorescent, while the derivatives of coumarin show intense
fluorescence, containing a push–pull electron system formed through the incorporation
of different electron-absorbing and electron-donating groups. The derivatives possess the
advantages of structural adjustment, high quantum yield, large Stokes shift, and excellent
photostability,
Molecules 2023, 27, x FOR PEER REVIEW which can sequester metal ions to enhance the fluorescence performance.
17 of 39
Therefore, they can be widely used to compose metal ion fluorescent probes for the detection
of heavy metal ions (Scheme 2d).

3.4.1. Fluorescent
3.4.1. Fluorescent Probes
Probes toto Detect
Detect Hg Hg2+2+

As shown
As shown in in Figure
Figure 11,11, DAC-Hg
DAC-Hg is is aa coumarin-based
coumarin-based fluorescent
fluorescent probe probe modified
modified
with sulfhydryl groups [89]. It can identify Hg 2+2+with high
with sulfhydryl groups [89]. It can identify Hg with high selectivity and sensitivityselectivity and sensitivity in
PBS buffer, displaying a “turn-off” fluorescence effect. The color
in PBS buffer, displaying a “turn-off” fluorescence effect. The color varies from cyan tovaries from cyan to nearly
weak yellow
nearly (non-fluorescent),
weak yellow (non-fluorescent),with awithdetection limit limit
a detection of 5.0ofnM. The application
5.0 nM. The application of this
of
method
this methodin analyzing
in analyzing environmental
environmental andandseafood
seafoodsamples
samplesyielded
yielded satisfactory resultsresults
(range of
(range of 96.2–105.0%),
96.2–105.0%), offering
offering aa promising
promising approach
approachfor forHg Hg2+2+ detection
detection and and potential
potential
applications in
applications in sensing
sensing other
other heavy
heavy and and transition
transition metalmetal ions.
ions. HCDC
HCDC was was amended
amended withwith
dimethylthiocarbamate moieties, serving as
dimethylthiocarbamate as aa sensor
sensor forfordetecting
detectingHg Hg2+ 2+ HEPES buffer
in HEPES buffer
(5 M,
(5 M, pH
pH == 7.4) medium [90]. This sensor triggers a switch from the thioester thioester group
group toto the
the
ester group
ester group of of the
the probe
probe andand turns
turns onon blue
blue fluorescence.
fluorescence. Notably,
Notably, the the response
response changes
changes
become significantly
become significantly more pronounced
pronounced under under the the aid
aid of
of HH22O22 (about 350-fold stronger),
with aa detection
with detection limit
limit of
of 0.3
0.3 nM.
nM. The The researchers
researchers further
further accomplished
accomplished real real water
water sample
sample
determination.
determination. J.J. Isaad et al. [91] constructed
constructed aa novel novel coumarin
coumarin hydrazone
hydrazone fluorescent
fluorescent
probe,
probe,L, L,from
from7-diethylamino
7-diethylaminocoumarin-3-carbaldehyde
coumarin-3-carbaldehyde and
and 2-thiophenethylhydrazine.
2-thiophenethylhydrazine. It
is capable of detecting Hg 2+ 2+
in bis-tris buffer (10 mM, pH = 7.0, 0.5% DMSO), rendering a
It is capable of detecting Hg in bis-tris buffer (10 mM, pH = 7.0, 0.5% DMSO), rendering
red
a redshift in the
shift emission
in the emissionwavelength
wavelength fromfrom
423 to 423508tonm.
508 The
nm. burst of fluorescence
The burst intensity
of fluorescence in-
at 516 nm,
tensity accompanied
at 516 by a distinct
nm, accompanied by acolor change
distinct colorfrom
changeyellow
from toyellow
red, is clearly
to red, visible to
is clearly
the naked
visible eyenaked
to the and iseye
related
and to ICT andtod-d
is related ICTtransitions of the metal
and d-d transitions of cations.
the metal The detection
cations. The
limit is 5.15
detection nMisand
limit it nM
5.15 has and
beenitsuccessfully applied to applied
has been successfully water samples.
to water samples.

Figure 11. The

Figure 11. The structures
structures of
of probes
probes ((a)
((a) is DAC-Hg, (b)
is DAC-Hg, (b) isis HCDC,
HCDC,(c)
(c)isisL).
L).

3.4.2. Fluorescent Probes to Detect Cd2+ and Pb2+

A novel chemochromic sensor composed of chalcone-modified coumarin, 1a, was
proposed for selective and sensitive recognition toward Cd2+ in HEPES buffer medium (20
mM, ACN/H2O, 3:7, v/v, pH = 7.0) [92]. Based on the CHEF mechanism, this probe per-
 Molecules 2023, 28, 5689 17 of 38

3.4.2. Fluorescent Probes to Detect Cd2+ and Pb2+

A novel chemochromic sensor composed of chalcone-modified coumarin, 1a, was
FOR PEER REVIEW proposed for selective and sensitive recognition toward Cd2+ in HEPES buffer 18 ofmedium
39
(20 mM, ACN/H2 O, 3:7, v/v, pH = 7.0) [92]. Based on the CHEF mechanism, this probe per-
forms a significant color change (from yellow to colorless) along with a notable fluorescence
turn-on, with a detection limit of 5.84 × 10−8 M. The novel coumarin-type Schiff base sen-
displaying intramolecular
sor, knowncharge
as probetransfer (ICT) and
1, can differentiate Cdleading to charge
2+ in the THF/H separation
2 O (1:1, v/v) systemin thea low
with
excited state due to their push–pull character as a π-conjugated system. This ICT results
detection limit of 0.114 µM, which is attributed to the inhibition of the C=N isomerization
in a red shift in theeffect [93]. Aminocoumarins
absorption of the receptorexhibit an interesting
bands behavior in
and a decrease inpolar solvents,
photon displaying
emission
intramolecular charge transfer (ICT) and leading to charge separation in the excited state
efficiency, confirming the binding of metals [94]. Keeping all these advantages of amino-
due to their push–pull character as a π-conjugated system. This ICT results in a red shift in
coumarins in view,the inabsorption
continuation
of the with work
receptor bandsinand
thisa decrease
ongoinginvibrant field, three
photon emission amino-
efficiency, confirm-
substituted coumarin receptors
ing the binding of(C1–C3) were
metals [94]. reported
Keeping that
all these show selective
advantages and sensitive
of aminocoumarins in view, in
binding with Pb2+ in continuation
ACN [95]. with
In work in thisall
addition, ongoing
of thevibrant field, three
substituted amino-substituted
amine derivatives were coumarin
receptors (C1–C3) were reported that show selective and sensitive binding with Pb2+ in
common bioactive substances, which facilitates the further application of the probes for
ACN [95]. In addition, all of the substituted amine derivatives were common bioactive
human metabolomics studies.
substances, Thefacilitates
which specificthestructures of the probes
further application are for
of the probes shown
human inmetabolomics
Figure
12. studies. The specific structures of the probes are shown in Figure 12.

Figure 12. The structures

Figureof
12.probes ((a–e) are
The structures 1a, 1,((a–e)
of probes and are
C1–C3, respectively).
1a, 1, and C1–C3, respectively).

3.5. Fluorescent Probes Based on Imidazole, Benzoxazole, Pyrazole, and Other Azoles
3.5. Fluorescent Probes Based
Azoleson
areImidazole,
pentacyclicBenzoxazole, Pyrazole, nitrogen.
compounds containing and Other Azoles
The hybrid atoms in penta-
Azoles are pentacyclic compounds
cyclic compounds containing
contain lone nitrogen.
pairs, leading The hybrid
to the pentacyclic atoms ineasily
compounds penta-
forming
cyclic compounds contain lone pairs, leading to the pentacyclic compounds easily form- are
hydrogen and coordination bonds and having strong electron affinity potential. There
many electroluminescent devices developed based on them, which can emit high-energy
ing hydrogen and coordination bonds and having strong electron affinity potential. There
blue light or purple light. Thus, azoles are important photosensitive substances. Recently,
are many electroluminescent devicesprobes
numerous fluorescent developed based
have been on them,
developed basedwhich can emit
on imidazole, high-en-pyra-
benzoxazole,
ergy blue light or purple
zole, andlight.
other Thus, azoles
components forare
the important photosensitive
detection of heavy substances.
metals (Scheme 2e). Re-
cently, numerous fluorescent probes have been developed based on imidazole, benzoxa-
3.5.1. Imidazole-Based Fluorescent Probes
zole, pyrazole, and other components for the detection of heavy metals (Scheme 2e).
Imidazole is a collective term for pentameric aromatic heterocyclic compounds contain-
ing two interposition nitrogen atoms in the molecular structure, owing to the participation
3.5.1. Imidazole-Based
of theFluorescent Probes
undisposed electron pair of the nitrogen atom in the ring in cyclic conjugation. These
Imidazole is a collective term for pentameric aromatic heterocyclic compounds con-
taining two interposition nitrogen atoms in the molecular structure, owing to the partici-
pation of the undisposed electron pair of the nitrogen atom in the ring in cyclic conjuga-
tion. These characteristics induce lower electron density of the nitrogen atom, easier de-
Molecules 2023, 28, 5689 18 of 38

characteristics induce lower electron density of the nitrogen atom, easier departure of the
hydrogen on this nitrogen atom, and more effective binding to metal ions.
As shown in Figure 13, probe NIS was synthesized by one-step reaction between
2,3-naphthalenediamine and imidazole-2-carboxaldehyde [96]. It selectively and sensi-
tively recognizes Cd2+ in HEPES buffer (EtOH/H2 O = 9:1, v/v, pH = 7.4), entraining
the charge transfer and chelation effects to turn on the fluorescence internally, yielding
a blue shift of the maximum emission peak of 74 nm, presumably due to the combined
effects of the ICT and CHEF mechanisms. By monitoring the variation in the fluorescence
intensity ratio at 398 and 472 nm (Ex.342 nm), NIS is able to monitor Cd2+ with a detection
limit of 3.87 × 10−7 M. It has also been successfully utilized for the detection of human
liver cancer cells (SMMC-7721), zebrafish, and other in vivo tissues. BPC is an imidazole-
based fluorescent probe modified with 4-cyanobiphenyl [97]. It can recognize Cd2+ in
ACN/Tris–HCl buffer (3:2, v/v, pH = 7.4), eliciting a significant color change (from colorless
to yellow), fluorescence turn-on at 547 nm, and has a detection limit of
1.05 × 10−8 M. The 1:1 complex formation between BPC and Cd2+ can block both isomeriza-
tion of C-N and the ESIPT process; meanwhile, it enhances the molecular rigidity, resulting
in chelation-enhanced fluorescence (CHEF). A highly green fluorescent phenothiazine-
based imidazolium ionic liquid sensor, [PTZ-SB][Br], was synthesized [98]. The sensor
can recognize Cd2+ in the THF/H2 O (1:9, v/v) system, achieving an incredible 38.1-fold
increase in fluorescence intensity with a detection limit of 3.8 × 10−7 M. Investigators
demonstrated that this change was due to the aggregation-induced enhanced emission
(AIEE) phenomenon. In order to broaden the applicability of the sensor in field test-
ing, a fluorescent paper strip has also been developed and successfully applied to water
sample detection. IHL is a new salicylhydrazone-anchored imidazolyl derivative [99].
This probe exhibits excellent biological potential for the identification of Cd2+ in the
DMSO/H2 O (9:1, v/v) system, showing a new absorbance at the 354 nm wavelength based
on metal-to-ligand charge transfer (MLCT) and C=N isomerization. The detection limit is
0.4 × 10−10 M and it has been successfully employed in conducting in vitro fluorescence
imaging of zebrafish embryos. L1 and L2 are two probes modified with ferrocene and
pyridine, which can switch the selective recognition from Hg2+ to Pb2+ via switching the
solvent system [100]. L1 and L2 display highly selective recognition of Hg2+ over a red shift
in the MeOH/H2 O (1:1, v/v) system, with immense brightness and remarkable fluorescence
quenching, and detection limits of 7.6 × 10−6 and 6.7 × 10−6 M, respectively. Meanwhile,
a similar UV response was induced by adding Pb2+ in the ACN system, but revealing
great fluorescence enhancement (CHEF = 25 for L1 and 33 for L2) and detection limits of
8.5 × 10−6 and 2.5 × 10−6 M, respectively. The PET mechanism is responsible for their fluo-
rescence changes. Compound 1 was investigated based on 4-hydroxy-3-nitrobenzaldehyde
and 9,10-phenanthrenequinone [101]. It possesses a highly sensitive (detection limit of
45.76 nM) and rapid response (within 5 s) towards Hg2+ in the DMF/PBS buffered solution
(1:4, v/v, pH = 7.4) system, accompanied with variation in the turn-on blue fluorescence.
In addition, researchers have successfully employed it in the determination of real water
samples, with recoveries of 91–106% and RSDs of less than 2.5%.

3.5.2. Benzoxazole-Based Fluorescent Probes

Benzoxazole is similar to imidazole in its structural characteristics, with excellent
metal ion-chelating properties that offer broader application prospects. L is a cyclophane
macrocycle containing the 1,3-bis(benzo[d]oxazol-2-yl)phenyl(BBzB) fluorophore and an
aliphatic tetra-amine chain to form the macrocyclic skeleton [102]. The sensor is a selective
PET-regulated chemosensor for Cd2+ in the ACN/H2 O (4:1, v/v) system, with detection
limits as low as 0.03 ppm. An NBD-based (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) flu-
orescent probe, NBDT, was fabricated with extraordinary specificity and sensitivity for
Cr3+ [103]. It works in the DMSO/H2 O (9:2, v/v) system over a wide pH range and cycle
stability, showing a color change (from purple to red) and a blue shift (from 548 nm to
522 nm). The detection limit is 0.041 µM. In addition, researchers have successfully ap-
Molecules 2023, 28, 5689 19 of 38

plied NBDT in detecting exogenous Cr3+ in MDA-MB-231 (human breast cancer cells),
HepG2 (human liver cancer) cells, and zebrafish embryonic cells. CY is an imidazole
class fluorescent probe structured with a semi-flowering anthocyanine [104]. It specifi-
cally identifies Hg2+ in the DMSO/H2 O (7:3, v/v) system, displaying a fluorescence-on
response with a detection limit of 1.61 × 10−7 M. This probe was successfully employed
in real water sample detection. A mercury ion-specific fluorescent probe, NBD-MPA, was
developed by a simple one-step reaction of commercial substrates of 4-chloro-7-nitro-2,1,3-
benzoxadiazole and 1-(2-aminoethyl)-4-methylpiperazine [105]. The probe senses Hg2+ in
ACN/HEPES buffer solution (1:9, v/v), provoking a red shift of the weak emission peak at
550 to 580 nm and turning on strong fluorescence, while the color shifts from yellow to pink
independent of other metal cations, with a detection limit of 9.2 × 10−7 M. Researchers
further employed the probes successfully for Hg2+ quantification in tap water, soil, green
tea, and sea shrimp, showing promising applications. BTS, a probe based on 4-(benzo [d]
thiazol-2-yldiazenyl) naphthalene-1,5-diol, was synthesized [106]. The sensor can recognize
Pb2+ in the DMSO/H2 O (1:4, v/v) system, displays a marked spontaneous color change
from blue to pink, and has a detection limit of 0.67 µM. In addition, test strips have also
been developed for its utilization as a rapid colorimetric chemical sensor, which have been
successfully applied in real water samples. The specific structures of the probes are 20
Molecules 2023, 27, x FOR PEER REVIEW shown
of 39
in Figure 14.

Figure 13.
Figure 13. The
The structures
structures of
of probes
probes ((a–g)
((a–g) are
are NIS,
NIS, BPC,
BPC, [PTZ-SB][Br],
[PTZ-SB][Br], IHL,
IHL, L1,
L1,L2,
L2,and
andcompound
com-
pound 1, respectively).
1, respectively).

3.5.2. Benzoxazole-Based Fluorescent Probes

Benzoxazole is similar to imidazole in its structural characteristics, with excellent
metal ion-chelating properties that offer broader application prospects. L is a cyclophane
macrocycle containing the 1,3-bis(benzo[d]oxazol-2-yl)phenyl(BBzB) fluorophore and an
aliphatic tetra-amine chain to form the macrocyclic skeleton [102]. The sensor is a selective
PET-regulated chemosensor for Cd2+ in the ACN/H2O (4:1, v/v) system, with detection lim-
its as low as 0.03 ppm. An NBD-based (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) fluores-
 showing promising applications. BTS, a probe based on 4-(benzo [d] thiazol-2-yldiazenyl)
naphthalene-1,5-diol, was synthesized [106]. The sensor can recognize Pb2+ in the
DMSO/H2O (1:4, v/v) system, displays a marked spontaneous color change from blue to
pink, and has a detection limit of 0.67 µM. In addition, test strips have also been developed
for its utilization as a rapid colorimetric chemical sensor, which have been successfully
Molecules 2023, 28, 5689 20 of 38
applied in real water samples. The specific structures of the probes are shown in Figure
14.

Figure 14.
Figure 14. The structures of
The structures of probes
probes ((a–e)are
((a–e)are L,
L, NBDT,
NBDT, CY,
CY, NBD-MPA,
NBD-MPA, and
and BTS,
BTS, respectively).
respectively).

3.5.3. Pyrazole-Based Fluorescent

3.5.3. Pyrazole-Based Fluorescent Probes
Probes
Pyrazoles and their derivatives
Pyrazoles and their derivatives are are considered
considered asas promising
promising fluorescent
fluorescent compounds
compounds
due to their excellent photophysical properties, including high fluorescence
due to their excellent photophysical properties, including high fluorescence quantum yields
quantum
and blue light emission with long fluorescence lifetimes. As shown in Figure
yields and blue light emission with long fluorescence lifetimes. As shown in Figure 15, a 15, a fluores-
cent sensor sensor
fluorescent based on pyrazoline-based
based compound
on pyrazoline-based 5-(4-methylphenyl)-3-(5-methylfuran-2-
compound 5-(4-methylphenyl)-3-(5-methyl-
yl)-1-phenyl-4, 5-dihydro-1H-pyrazole, PY, has been synthesized
furan-2-yl)-1-phenyl-4, 5-dihydro-1H-pyrazole, PY, has been synthesized for the selective
for thedetection
selective
of Cd 2+ in water samples [107]. The sensor analyzes Cd2+ in MeOH/PBS buffer (pH = 7)
detection of Cd in water samples [107]. The sensor analyzes Cd in MeOH/PBS buffer
2+ 2+
system,
(pH = 7)induces
system,fluorescence quenchingquenching
induces fluorescence with a detection
with alimit of 0.09limit
detection µM, and hasµM,
of 0.09 beenand
ap-
plied successfully for the determination of water samples (tap water, river
has been applied successfully for the determination of water samples (tap water, river water and bottled
water).
water andThebottled
dominant process
water). Thefor fluorescence
dominant quenching
process is attributed
for fluorescence to the intermolecular
quenching is attributed
PET mechanism. A new tripodal fluorogenic and chromogenic receptor, 5-bromosalicyl
to the intermolecular PET mechanism. A new tripodal fluorogenic and chromogenic re-
hydrazone appended pyrazole, BPP, has been designed and synthesized [108]. The flu-
ceptor, 5-bromosalicyl hydrazone appended pyrazole, BPP, has been designed and syn-
orescent probe can recognize Cd2+ in the DMSO/H2 O2+(9:1, v/v) system, with the color
thesized [108]. The fluorescent probe can recognize Cd in the DMSO/H2O (9:1, v/v) sys-
of the solvent switching from light yellow to light yellow-green, and a detection limit of
tem, with the color of the solvent switching from light yellow to light yellow-green, and a
0.02 nM. In addition, the outcome of fluorescence imaging assays in HeLa cells and zebrafish
detection limit of 0.02 nM. In addition, the outcome of fluorescence imaging assays in
embryos suggested that BPP could be useful in biological systems as a potential chemical
HeLa cells and zebrafish embryos suggested that BPP could be useful in biological sys-
device. ADMPA was proposed as another novel highly sensitive and rapid-response fluo-
tems as a potential chemical device. ADMPA was proposed as another novel highly sen-
rescent probe based on o-aminophenol and 2,9-dimethyl-1,10-o-phenanthroline [109]. The
sitive and rapid-response fluorescent probe based on o-aminophenol and 2,9-dimethyl-
probe can recognize Cd2+ in the DMF/H2 O (3:7, v/v) system and induce probe fluorescence
1,10-o-phenanthroline [109]. The probe can recognize Cd2+ in the DMF/H2O (3:7, v/v) sys-
to turn on, owing to the suppression of PET and CHEN isomerization. The detection limit
tem and induce probe fluorescence to turn on, owing to the suppression of PET and CHEN
is as low as 29.3 nM. This method has been successfully utilized for the determination
isomerization.
of The detection
real water samples limit is as low
with satisfactory as 29.3 nM.
recoveries. This method
H. Rahimi has been
et al. [110] successfully
demonstrated a
utilized for the determination of real water samples with satisfactory
novel fluorescent probe, 3, containing pyridine-2, 6-dicarboxamide. The probe recognizes recoveries. H.
Rahimi
Pb et al. and
2+ in ACN [110]shows
demonstrated a novel
fluorescence fluorescent
quenching, withprobe, 3, containing
a detection pyridine-2,
limit of 2.31 × 10−6 M. 6-
Ease of synthesis and impressive sensitivity and selectivity are the main features of this
cation chemosensor.
 Molecules 2023, 27, x FOR PEER REVIEW 22 of 39

dicarboxamide. The probe recognizes Pb2+ in ACN and shows fluorescence quenching,
Molecules 2023, 28, 5689 21 ofand
with a detection limit of 2.31 × 10−6 M. Ease of synthesis and impressive sensitivity 38
selectivity are the main features of this cation chemosensor.

Figure15.
Figure 15.The
Thestructures
structuresofofprobes
probes((a–d)
((a–d)are
arePY,
PY,3,3,BPP
BPPand
andADMPA,
ADMPA,respectively).
respectively).

3.6.
3.6.Thiourea-Based
Thiourea-BasedFluorescent
FluorescentProbes
Probes
The
Thethiourea
thioureastructure
structurecontains
containsthiocarbonyl
thiocarbonylC=S, C=S,which
whichshows
showsdifferences
differencesininshape
shape
and
andenergy
energy between
between thethe 2p2p orbital
orbitalofofthetheC-atom
C-atom and and thethe
3p 3p orbital
orbital of the
of the S-atom
S-atom in
in thio-
thiocarbonyl, with less orbital overlap. It allows a weaker Π-bond
carbonyl, with less orbital overlap. It allows a weaker Π-bond in the thiocarbonyl group in the thiocarbonyl
group and unique
and unique coordination
coordination ability (Scheme
ability (Scheme 2f). As
2f). As shown shown 16,
in Figure in aFigure
novel 16, a novel
fluorometric
fluorometric probe, NT, was designed to detect Cd 2+ in ACN [111]. It could inhibit
probe, NT, was designed to detect Cd in ACN [111]. It could inhibit immediate strong
2+
immediate strong green
green fluorescence fluorescence
and turned and turned
on intensive greenon intensive green
fluorescence owing fluorescence owing
to the suppression
toofthe suppression of C=N isomerization by Cd 2+ . S. S. Samanta et al. [112] presented a
C=N isomerization by Cd2+. S. S. Samanta et al. [112] presented a fluorescent probe, H2L,
2+ in MeOH, turning on strong
fluorescent probe, H 2 L, which was capable
which was capable of recognizing Cd in MeOH, 2+ of recognizing Cd
turning on strong fluorescence with a
fluorescence with
detection limit ofa2.67
detection
× 10−8 limit
M, and was ×
of 2.67 10−8 M, and
applicable was beverage,
in food, applicableandin food, beverage,
environmental
and
detection. A novel naphthalimide derivative,2+TND, modified with aminothiourea,with
environmental detection. A novel naphthalimide derivative, TND, modified was
aminothiourea, was presented
presented for acquiring Pb2+ inforthe
acquiring
ACN/HPb in the ACN/H2 O (1:1, v/v) system [113].
2O (1:1, v/v) system [113]. It displays a clear
It displays a clear color change (from light green to yellow) and turn-on fluorescence
color change (from light green to yellow) and turn-on fluorescence based on the superior-
based on the superiorities of naphthalimide, which has the properties of great stability and
ities of naphthalimide, which has the properties of great stability and easy modification.
easy modification. The detection limit is 4.7 nM and it has been successfully employed
The detection limit is 4.7 nM and it has been successfully employed in the detection of
in the detection of water samples with a spiked recovery of 100.54–113.68%. An NIR
water samples with a spiked recovery of 100.54–113.68%. An NIR fluorescent probe for
fluorescent probe for the fast determination Pb2+ , probe 1, was synthesized based on a
the fast determination Pb2+, probe 1, was synthesized based on a carbonyl hydrazide de-
carbonyl hydrazide derivative modified with a dicyanoisophorone backbone [114]. The
rivative modified with a dicyanoisophorone backbone [114]. The probe with2+the thio-
probe with the thiophene-2-carbohydrazide group is capable of capturing Pb in the
phene-2-carbohydrazide group is capable of capturing Pb2+ in the ACN/EtOH/HEPES sys-
ACN/EtOH/HEPES system (1:1:2, v/v/v, pH = 7.0), with a maximum emission wavelength
tem (1:1:2, v/v/v, pH = 7.0), with a maximum emission wavelength of 670 nm. It has been
of 670 nm. It has been successfully utilized in real water samples, with a detection limit
successfully utilized in real water samples, with a detection limit of 1.65 nM. A novel tri-
of 1.65 nM. A novel triamine-thiophene-aminothiourea fluorescent probe, TPA-TSC, was
amine-thiophene-aminothiourea
proposed for excellent selectivity towardfluorescent
Hg2+ probe, TPA-TSC, system
in the ACN/PBS was proposed forpH
(1:1, v/v, excellent
= 7.4),
selectivity
with toward
the lowest Hg limit
detection
2+ in the ACN/PBS
(0.14 system (1:1,
nM) yet reported [115].v/v, pH = 7.4),
It exhibited with the
a turn-off lowest
response
by forming a stable complex for a brief period (<30 s). In addition, the investigators
successfully applied the probes to perch, sailfish, and different water samples.
Molecules 2023, 27, x FOR PEER REVIEW 23 of 39

detection limit (0.14 nM) yet reported [115]. It exhibited a turn-off response by forming a
Molecules 2023, 28, 5689 22 of 38
stable complex for a brief period (<30 s). In addition, the investigators successfully applied
the probes to perch, sailfish, and different water samples.

Figure 16. The

The structures of probes
structures of probes ((a–e)
((a–e) are
are NT,
NT, H
H2L, TND, probe 1 and TPA-TSC, respectively).
Figure 16. 2 L, TND, probe 1 and TPA-TSC, respectively).

3.7. TPE-Based Fluorescent Probes

propeller-shaped structure
The TPE molecular architecture features a propeller-shaped structure with
with four
four ben-
ben-
zene rings connected to the middle vinyl group by C-C single bonds, and the benzene
rings rotate and vibrate freely around the single bond (Scheme 2g). The The phenyl
phenyl ring
ring re-
re-
mains in a low fluorescence state owing to the energy consumption caused by rotational
vibrations
vibrations when
when it it is
is in
in solution. However, when
solution. However, when the the molecule
molecule occupies
occupies an an aggregated
aggregated
state, such
state, such as
as aaconcentrated
concentratedsolution
solutionorora asolid
solidstate,
state,thethe non-radiative
non-radiative relaxation
relaxation willwill
be
be suppressed due to intermolecular interactions. These interactions
suppressed due to intermolecular interactions. These interactions inhibit the energy-con- inhibit the energy-
consuming
suming motion
motion of theof the benzene
benzene ringring molecules,
molecules, eventually
eventually bringing
bringing outoutthethe emission
emission of
of excited-state energy through fluorescence. TPE is a well-known
excited-state energy through fluorescence. TPE is a well-known luminescent material luminescent material
with
with AIE properties.
AIE properties. However,
However, TPE TPE aggregates
aggregates havehave a limited
a limited emission
emission wavelength,
wavelength, which
which re-
restricts
stricts furtherinvestigation.
further investigation.ToToovercome
overcomethis
thislimitation,
limitation,aa TPE-based
TPE-based fluorescent
fluorescent probe
probe
called TPE-Hg
called TPE-Hg was was synthesized
synthesized by by extending
extending the
the conjugation
conjugation of of the
the TPE
TPE fluorophore
fluorophore withwith
a hydroxyethyl sulfide portion [116]. This probe exhibits a large Stokes
a hydroxyethyl sulfide portion [116]. This probe exhibits a large Stokes shift (2032+nm), shift (203 nm),
strong anti-interference ability, and high sensitivity and specificity in
strong anti-interference ability, and high sensitivity and specificity in detecting Hg . Indetecting Hg 2+ . Ina
a THF/HEPES system (20 mM, pH = 7.3) (1:9, v/v),
THF/HEPES system (20 mM, pH = 7.3) (1:9, v/v), the probe undergoes the probe undergoes a color change
a color change from
from green to yellow, with a detection limit as low as 7.548
green to yellow, with a detection limit as 2+
× 10−7 M. It has been suc-
low as 7.548 × 10−7 M. It has been successfully
cessfully utilized for the detection of Hg in seafood and tea, with reliable recoveries
utilized for the detection of Hg2+ in seafood and tea, with reliable recoveries (89.88–
(89.88–105.06%) and reasonable relative standard deviations (2.26–9.71%). The test strips
105.06%) and reasonable relative standard deviations (2.26–9.71%). The test strips ob-
obtained on the basis of TPE-Hg also exhibit rapid detection properties. Another selective
tained on the basis of TPE-Hg also exhibit rapid detection properties. Another selective
fluorescent probe for Hg2+ , TPE-M, was developed via incorporating a dithiocarbonyl
fluorescent probe for Hg2+, TPE-M, was developed via incorporating a dithiocarbonyl
group (3-mercaptopropionic acid) [117]. Reaction of TPE-M with Hg2+2+ in the MeOH/PBS
group (3-mercaptopropionic acid) [117]. Reaction of TPE-M with Hg in the MeOH/PBS
(20 mM, pH = 7.4) (3:7, v/v) buffer system leads to the release of an AIE active precursor,
(20 mM, pH = 7.4) (3:7, v/v) buffer system leads to the release of an AIE active precursor,
which results in significant fluorescence enhancement. The detection limit is 4.16 × 10−6 M
and it has been successfully implemented in real food samples such as shrimp, crab, and tea
with good recoveries (93.47–105.4%). A new ratiometric fluorescent probe to recognize Pb2+ ,
TPE-MC-P, was designed and synthesized by introducing a spiro-pyran (SP) unit through
Molecules 2023, 27, x FOR PEER REVIEW 24 of 39

which results in significant fluorescence enhancement. The detection limit is 4.16 × 10−6 M
Molecules 2023, 28, 5689 and it has been successfully implemented in real food samples such as shrimp, crab, 23 of
and38
tea with good recoveries (93.47–105.4%). A new ratiometric fluorescent probe to recognize
Pb2+, TPE-MC-P, was designed and synthesized by introducing a spiro-pyran (SP) unit
through
the the phototransformation
phototransformation technique
technique [118]. [118].identified
The probe The probe Pb2+identified
in the THF/H Pb2+ 2in the
O (1:9,
THF/H
v/v) 2O (1:9,
system, v/v) system,
followed followed
by a burst of redbyfluorescence
a burst of red fluorescence
of the MC unit (E ofmthe MCnm)
= 635 unitand
(Eman=
635 nm) and an
enhancement ofenhancement
the blue-green offluorescence
the blue-green fluorescence
of the TPE unit of the
(Em = TPE
480 nm)unit in
(Em = 480 nm)
TPE-MC-P.
in TPE-MC-P.
By monitoring the By fluorescence
monitoring the fluorescence
variation behaviorvariation behavior
of the probe withof the probe
increasing with in-
concentra-
creasing
tions of Pb 2+ , a new high-efficiency
concentrations of Pb2+, a newandhigh-efficiency
high-accuracy and high-accuracy
detection methoddetection method
with a detection
with aofdetection
limit 0.27 µM was limitestablished
of 0.27 µMandwassuccessfully
established and successfully
applied applied
to potable to potable The
water detection. wa-
ter detection.
specific The specific
structures structures
of the probes of the in
are shown probes
Figureare17.
shown in Figure 17.

Figure 17.
Figure 17. The structures of
The structures of probes
probes ((a)
((a) is
is TPE,
TPE, (b)
(b) is
is TPE-M,
TPE-M, (c)
(c) is
is TPE-MC-P).
TPE-MC-P).

3.8. Thiophene-Based Fluorescent Probes

Thiophene is widely employed as the linking part of compounds due to its simplicity
of structure, facile modification,
modification, and singular
singular property
property (Scheme
(Scheme 2h). 2h). A new simple and
efficient
efficient oligothiophene-based colorimetric and
oligothiophene-based colorimetric and ratiometric
ratiometric fluorescent
fluorescent probe,probe, 33 TS,
TS, has
been developed for the highly sensitive and fast detection of Hg 2+ in water, soil, and
been developed for the highly sensitive and fast detection of Hg in water, soil, and sea-
2+

seafood
food [119].[119]. It works
It works in EtOH/H
in the the EtOH/H 2 O system
2O system (1:1, v/v) v/v)
(1:1,via thevia the reaction
reaction of thioacetals,
of thioacetals, which
which
elicits a significant change in the color of the probe from colorless to yellow, ato100
elicits a significant change in the color of the probe from colorless yellow,
nm reda
100
shiftnm red spectrum,
of the shift of theand
spectrum, andfluorescence
intensive intensive fluorescence
enhancement. enhancement.
The concentrationThe concentra-
of Hg2+
tion
can be Hg2+ can beby
of determined determined
observing theby observing
variation inthe thevariation
fluorescence in the fluorescence
intensity ratio atintensity
550 and
ratio at 550 andEx.360
450 nm under −8 M. It
× 10success-
450 nm under nm, withEx.360 nm, with
a detection limitaofdetection
up to 1.03 limit
× 10of−8 up
M. to 1.03been
It has
has
fullybeen successfully
implemented inimplemented in detecting
detecting various water various
samples,water samples,soils,
agricultural agricultural soils,
and aquatic
and aquatic products. Another probe, 1.1, was reported as a novel
products. Another probe, 1.1, was reported as a novel fluorescent chemosensor based on fluorescent chemosensor
based on naphthyridine-boronic
naphthyridine-boronic acid-thiophene
acid-thiophene derivatives derivatives
[120]. This[120].probeThis probea displays
displays a
highly se-
highly selective fluorescence interruption for Hg 2+ in the MeOH/H O system by means
lective fluorescence interruption for Hg2+ in the MeOH/H2O system 2by means of the PET
2+ is enhanced at
of the PET mechanism. Interestingly, the sensitivity of 1.1 toward
mechanism. Interestingly, the sensitivity of 1.1 toward Hg is enhanced at least 7-fold in
2+ Hg
least 7-fold in the presence of physiological concentrations of D-fructose, which may be
attributed to the synergistic binding of D-fructose along with mercury ions to the sensor.
This is the first proposed D-fructose-mercury chemosensor until now, which facilitates the
application of the probe in the food industry, for instance to detect mercury contamination
Molecules 2023, 27, x FOR PEER REVIEW 25 of 39

the presence of physiological concentrations of D-fructose, which may be attributed to the

Molecules 2023, 28, 5689 synergistic binding of D-fructose along with mercury ions to the sensor. This is the first
24 of 38
proposed D-fructose-mercury chemosensor until now, which facilitates the application of
the probe in the food industry, for instance to detect mercury contamination in high-fruc-
tose corn syrup. Recently, hydrazones have garnered significant attention in chemistry
in high-fructose corn syrup. Recently, hydrazones have garnered significant attention
due to the presence of reactive amino-type nitrogen in the imine core unit. Attributable to
in chemistry due to the presence of reactive amino-type nitrogen in the imine core unit.
their similarities with carbonyl-containing compounds, hydrazones can participate in a
Attributable to their similarities with carbonyl-containing compounds, hydrazones can
huge variety of typically synthetic reactions, including free radical reactions, cyclo-addi-
participate in a huge variety of typically synthetic reactions, including free radical reactions,
tion reactions, and transition metal-based reactions [121]. They show an extensive array
cyclo-addition reactions, and transition metal-based reactions [121]. They show an exten-
of intriguing organic activities and pharmacological behaviors. Based on these properties,
sive array of intriguing organic activities and pharmacological behaviors. Based on these
NAPABTHNAPABTH
properties, was designedwasand synthesized
designed using thiophene-functionalized
and synthesized hydrazonehy-
using thiophene-functionalized as
a chemical
drazone as probe for specifically
a chemical probe for sensing Pb sensing
specifically
2+ in the DMSO system
Pb2+ in [122]. system
the DMSO It evokes a light
[122]. It
yellow to pink dye color with a very low detection limit (1.06 ppm) via the ICT and
evokes a light yellow to pink dye color with a very low detection limit (1.06 ppm) via the LMCT
processes.
ICT The specific
and LMCT structures
processes. of thestructures
The specific probes areofshown in Figure
the probes 18. in Figure 18.
are shown

Figure 18.
Figure 18. The
The structures
structures of
of probes
probes ((a)
((a) is
is 33 TS,
TS, (b)
(b) is
is 1.1,
1.1, (c)
(c) isisNAPABTH).
NAPABTH).

3.9.
3.9. Naphthoimide-Based
Naphthoimide-Based Fluorescent
Fluorescent Probes
Probes
With
With strong yellow-green fluorescence, high
strong yellow-green fluorescence, high fluorescence
fluorescence quantum
quantum yields,
yields, and
and easy
easy
modification, naphthalimide and its derivatives have been widely used as fluorophores
modification, naphthalimide and its derivatives have been widely used as fluorophores to
to develop
develop many
many fluorescent
fluorescent dyesdyes
(Scheme(Scheme 2i).
2i). As As shown
shown in 19,
in Figure Figure 19, an effective
an effective morpho-
morpholine-type naphthalimide probe, N-p-chlorophenyl-4-(2-aminoethyl)morpholine-
line-type naphthalimide probe, N-p-chlorophenyl-4-(2-aminoethyl)morpholine-1,8-naph-
1,8-naphthalimide (CMN), has been developed as a lysosome-targeted fluorometric sensor3+
thalimide (CMN), has been developed as a lysosome-targeted fluorometric sensor for Cr
for Cr3+ [123]. It functions in MeOH following a marked color change (yellowish color
[123]. It functions in MeOH following a marked color change (yellowish color darkening),
darkening), with a detection limit of 0.68 µM. Due to the N-atom of morpholine being
with a detection limit of 0.68 µM. Due to the N-atom of morpholine being directly in-
directly involved in complex formation, CMN emits a fluorescence response through the
volved in complex formation, CMN emits a fluorescence response through the inhibition
inhibition of PET. Significantly, cellular confocal microscopic research indicated that the in-
of PET. Significantly, cellular confocal microscopic research indicated that the
troduction of the lysosome-targeted group of the morpholine moiety realized the capability
of imaging lysosomal trivalent metal ions in living cells for the first time. In another study,
probe 3 was designed as a quinoline-modified naphthalimide fluorescent probe [124]. The
probe is capable of Cr6+ recognition in the ACN/HEPES (10 mM, pH = 7.4) (1:9, v/v) sys-
tem, with a rapid fluorescence burst via the internal filtration effect. The burst constant is
 introduction of the lysosome-targeted group of the morpholine moiety realized the capa-
bility of imaging lysosomal trivalent metal ions in living cells for the first time. In another
Molecules 2023, 28, 5689 study, probe 3 was designed as a quinoline-modified naphthalimide fluorescent 25 probe
of 38
[124]. The probe is capable of Cr6+ recognition in the ACN/HEPES (10 mM, pH = 7.4) (1:9,
v/v) system, with a rapid fluorescence burst via the internal filtration effect. The burst con-
stant×is10
7.99 7.99
3 M×−10 3 M−1 and the detection limit is 1.15 µM. The results of spiked recovery
1 and the detection limit is 1.15 µM. The results of spiked recovery ex-
experiments
periments in in real
real water
water samples
samples showedpositive
showed positiveoutcomes.
outcomes. A A simple
simple water-soluble
water-soluble
naphthalimide-derived fluorescent dye with AIEE characteristics was reasonably con-
naphthalimide-derived fluorescent dye with AIEE characteristics was reasonably con-
structed based
structed based onon the
the twisted
twisted intramolecular
intramolecular charge
charge transfer
transfer (TICT)
(TICT) mechanism.
mechanism. NIDEANIDEA
was synthesized
was synthesized to to demonstrate
demonstrate thisthismechanism
mechanism[125].
[125].ItItreacts
reactswell
wellwith
withHgHg2+2+ in
in HEPES
HEPES
buffer (10
buffer (10mM,
mM,pH pH = 7.4),
= 7.4), specifically
specifically binding
binding to thetoN-unsubstituted
the N-unsubstituted naphthalimide
naphthalimide group
group to form a classical “imide-mercury-imide” structure. Moreover, the
to form a classical “imide-mercury-imide” structure. Moreover, the introduction of the introduction of
the diethanolamine moiety enhances the water solubility of the probe and allows
diethanolamine moiety enhances the water solubility of the probe and allows for the feature for the
feature
of AIEE,offollowing
AIEE, following
switching switching on of fluorescence,
on of fluorescence, with a detection
with a detection limit
limit of 46.7 nM.of 46.7 nM.
It works
It works
well well
in real in real
water water samples.
samples.

Figure 19.
Figure 19. The
The structures
structures of
of probes
probes ((a)
((a) is
is CMN,
CMN, (b)
(b) is
is probe
probe3,
3,(c)
(c)isisNIDEA).
NIDEA).

3.10.
3.10. Other
Other Scaffolds
Scaffolds
In
In summary,
summary,the thefield
fieldofoffluorescent
fluorescentprobes
probeshas witnessed
has witnessed significant
significant advancements
advancements in
the development of various scaffolds. These probes exhibit excellent selectivity,
in the development of various scaffolds. These probes exhibit excellent selectivity, sensi- sensitivity,
and real-time
tivity, detection
and real-time capabilities
detection for heavyfor
capabilities metals
heavy inmetals
food. However, a major drawback
in food. However, a major
is that many of these probes suffer from aggregate-induced
drawback is that many of these probes suffer from aggregate-induced quenchingquenching (ACQ), resulting
(ACQ),
in significant
resulting interference
in significant from either
interference theeither
from probesthethemselves or the background,
probes themselves thereby
or the background,
hindering their practical
thereby hindering applications.
their practical Moreover,
applications. the limited
Moreover, thespecificity of probesofremains
limited specificity probes
aremains
challengea challenge for their application in the quantitative analysis of heavy metals In
for their application in the quantitative analysis of heavy metals in food. in
particular, metal ions
food. In particular, from
metal thefrom
ions same thehomologous main group
same homologous main of the periodic
group table often
of the periodic table
exhibit indistinguishable
often exhibit responses
indistinguishable to the same
responses to thesignal,
same leading to a lacktoofa selectivity
signal, leading among
lack of selectivity
diverse fluorescent probes owing to their similar electronic configurations, coordination
among diverse fluorescent probes owing to their similar electronic configurations, coor-
numbers, and chemical properties. Thus, overcoming the contradictions between the
dination numbers, and chemical properties. Thus, overcoming the contradictions between
above chemical properties and sensing mechanisms will be significant to developing new
the above chemical properties and sensing mechanisms will be significant to developing
fluorescent probes.
new fluorescent probes.
3.10.1. Fluorescent Probes to Detect Cd2+
3.10.1. Fluorescent Probes to Detect Cd2+
As shown in Figure 20, a novel optical chemosensor, CM 1 (2,6-di((E)-benzylidene)-
As shown in Figure 20, a novel optical chemosensor, CM 1 (2,6-di((E)-benzylidene)-
4-methylcyclohexan-1), was designed to specifically detect Cd2+ [126]. It works well in
4-methylcyclohexan-1), was designed to specifically detect Cd2+ [126]. It works well in
aqueous media, initiates fluorescence turn-on with a detection limit of 19.25 nM, and
has been successfully employed in the detection of real water samples. A facile AIE
fluorescent probe, SAF, was developed to recognize Cd2+ in ACN aqueous solution (95:5,
v/v),exhibiting a large Stokes shift of 202 nm [127]. The probe presents high selectivity by
inhibiting the ESIPT process, leading to an observable blue shift and significantly enhanced
fluorescence, with the color changing from green to cyan. The recognition of Cd2+ is
 probe, SAF, was developed to recognize Cd2+ in ACN aqueous solution (95:5, v/v),exhib-
iting a large Stokes shift of 202 nm [127]. The probe presents high selectivity by inhibiting
the ESIPT process, leading to an observable blue shift and significantly enhanced fluores-
cence, with the color changing from green to cyan. The recognition of Cd2+ is completely
Molecules 2023, 28, 5689 26 of 38
free from the interference of Zn2+. The detection limit is 1.5 × 10−7 M and it has successfully
performed in real water samples. Throughout connecting a tetrahydro-[5]spiroene deriv-
ative fluorescent dye with 6-bis((quinolin-8-yloxy)methyl)pyridine,
completely free from the interference of Zn2+ . The detectionalimit novel × 10−7 M and it
is 1.5fluorescent
has successfully
sensor, PM, was designed performed in
and synthesized real
for water samples.
detection of CdThroughout
2+ [128]. The connecting
modification a tetrahydro-
of
[5]spiroene derivative fluorescent dye with 6-bis((quinolin-8-yloxy)methyl)pyridine, a
the tetrahydro-[5]spiroene dye in the probe offers a strong fluorescence signal in the visi-
novel fluorescent sensor, PM, was designed and synthesized for detection of Cd2+ [128].
ble region, high fluorescence quantum
The modification yield, and a largedye
of the tetrahydro-[5]spiroene Stokes
in theshift, which
probe offers contributes
a strong fluorescence
tremendously to the sensitivity
signal of the
in the visible sensor.
region, highPM works well
fluorescence quantumin the H2O/dioxane
yield, (1/19,shift,
and a large Stokes
v/v) system, exhibiting
whichturn-on
contributesfluorescence
tremendously with a significantly
to the large
sensitivity of the Stokes
sensor. shift at
PM works 163in the
well
2 O/dioxane (1/19, v/v)
nm. The limit of detection is 53 nM and it has been successfully utilized towards Cd2+large
H system, exhibiting turn-on fluorescence with a significantly
Stokes shift at 163 nm. The limit of detection is 53 nM and it has been successfully utilized
detection in commercially available foods, including drinking water and rice.
towards Cd2+ detection in commercially available foods, including drinking water and rice.

Figure 20. The structures

Figureof20.
probes ((a) is CM
The structures 1, (b)((a)
of probes is isSAF, (c)(b)isisPM).
CM 1, SAF, (c) is PM).

3.10.2. Fluorescent Probes to Detect Cr3+

3.10.2. Fluorescent Probes to Detect Cr3+
As shown in Figure 21, the ligand 2,6-bis(E)-4-methylbenzylidine)-cyclohexan-1-one
As shown in Figure
has been21, the ligand
synthesized as 2,6-bis(E)-4-methylbenzylidine)-cyclohexan-1-one
a fluorescence-on probe, sensor C, for the trace level detection
of Cr3+ Cr3+the
has been synthesized as a[129]. The probe selectively
fluorescence-on probe, responds
sensor C, to for in ACN
tracemedium based on the
level detection of ICT
mechanism, turning on fluorescence with a detection limit of 2.3 × 10−9 M. The probe
Cr [129]. The probe selectively responds to Cr in ACN medium based on the ICT mech-
3+ 3+
has been successfully applied to real water samples. Dansulfonyl chloride has drawn
anism, turning on fluorescence with aasdetection
widespread attention limitowing
a fluorophore of 2.3to×its10strong
−9 M. The probe has been
fluorescence, long emission
successfully applied to real water
wavelength samples.
(400–600 nm), large Dansulfonyl chloride
Stokes shift (330–350 nm),hasanddrawn widespreadBased
easy modification.
attention as a fluorophore owing to its strong fluorescence, long emission wavelength
on these considerations, DNSC-CTV was published as a novel cyclotrisveratrole-derived
(400–600 nm), largechemosensor
Stokes shiftmodified
(330–350 with dansyl
nm), andchloride [130]. It works Based
easy modification. Cr3+
well foron recognition
these con- in
ACN. A novel poly(methylene-carbamate) chemical sensor, HIMA, was prepared in a
siderations, DNSC-CTV was published as a novel cyclotrisveratrole-derived chemosen-
two-step reaction using hexamethylene diisocyanate, 2,4-dihydroxy benzaldehyde, and
sor modified with dansyl chloride
2-aminopheno, [130].
which couldIt works
detect Crwell for Cr
3+ cations 3+ recognition in ACN. A novel
in different solutions [131]. It shows specific
poly(methylene-carbamate) chemical
sensitivity in DMF/H2sensor, HIMA,
O (1:2, v/v), with awas prepared
detection limit ofin7.98 × 10−7 M,reaction
a two-step and has been
successfully employed in different potable water
using hexamethylene diisocyanate, 2,4-dihydroxy benzaldehyde, and 2-aminopheno, samples. A novel fluorescent probe,
which could detect Cr3+ cations in different solutions [131]. It shows specific sensitivity in It
ANT-In, was investigated based on anthracene and indole as the structural units [132].
has been demonstrated that aminoanthracene-based probes exhibit structural simplicity,
DMF/H2O (1:2, v/v),high
with a detection
quantum limit of stability,
yield, chemical 7.98 × 10and−7 M, and has been successfully em-
facilitate chemical modifications. Thus, the
ployed in different potable water samples. A novel fluorescent probe, ANT-In, was inves-
tigated based on anthracene and indole as the structural units [132]. It has been
x FOR PEER REVIEW 28 of 39

Molecules 2023, 28, 5689 27 of 38

demonstrated that aminoanthracene-based probes exhibit structural simplicity, high
quantum yield, chemical stability, and facilitate chemical modifications. Thus, the probe
can identify Cr3+ in a highly sensitive and selective manner in the ACN/HEPES buffer (7:3,
probe can identify Cr3+ in a highly sensitive and selective manner in the ACN/HEPES
v/v, pH = 7) system via(7:3,
buffer hydrolysis
v/v, pH = of the C=N
7) system via bond, turning
hydrolysis of the on
C=Nfluorescence
bond, turningin
onless than
fluorescence
one minute, withina less
lowthan
detection limitwith
one minute, of 0.2 µM,
a low and has
detection been
limit successfully
of 0.2 µM, and hasimplemented
been successfully
implemented
in potable water detection. in potable water detection.

Figure 21. The structures of The

Figure 21. structures
probes of probes
((a–d) ((a–d) are
are sensor C,sensor C, DNSC-CTV,
DNSC-CTV, HIMA andand
HIMA respectively).
ANT-In, respec-
ANT-In,
tively). 3.10.3. Fluorescent Probes to Detect Hg2+
As shown in Figure 22, a lysosome-targetable fluorescence sensor, Lyso-HGP, was
3.10.3. Fluorescent Probesand
designed to synthesized
Detect Hg2+based on 4-methyl-2,6-diformylphenol as a fluorophore [133].
2+
As shown inThe sensor22,
Figure is capable of acquiring Hg influorescence
a lysosome-targetable a HEPES buffered solution
sensor, (10 mM, pH
Lyso-HGP, was= 7.0,
DMSO 1%), forming a particularly fluorescent formyl-functionalized component (Lyso-
designed and synthesized based on 4-methyl-2,6-diformylphenol as a fluorophore [133].
HGP-CHO) and enhancing turn-on fluorescence by 180-fold just after 10 min. The detection
The sensor is capable
limit isof
asacquiring
low as 6.82 nM Hg2+ andinitahas
HEPES buffered applied
been successfully solution to (10 mM,drinking
different pH = 7.0,water
DMSO 1%), forming assays.a Also,
particularly
the sensorfluorescent formyl-functionalized
has been applied to monitor the subcellular component
distribution of Hg2+
(Lyso-
HGP-CHO) and specifically
enhancinglocalizedturn-on in fluorescence
the lysosomal compartment
by 180-foldinjust MCF7 human
after breastThe
10 min. cancer cells by
detec-
fluorescence microscopy. A new carbazole-based fluorescent probe (DTCB) was proposed
tion limit is as low as 6.82 nM and it has been successfully applied to different drinking
using the theory of mercury-initiated thiolate deprotection response [134]. The probe iden-
water assays. Also, the
tifies Hgsensor hasthioacetal
2+ -induced been applied to monitor
in the THF/H the subcellular distribution of
2 O mixture, evolving deep blue fluorescence
Hg specifically towards
2+ localized greenin fluorescence
the lysosomal compartment
and greatly strengthening in MCF7 humanintensity.
the fluorescence breast It cancer
presents
an excellent positive linear relationship with the concentration of Hg 2+ at 480 nm, with a
cells by fluorescence microscopy. A new carbazole-based fluorescent probe (DTCB) was
proposed using the detection
theory limitof as low as 2.05 × 10−7 M.
mercury-initiated Moreover,
thiolate the researchers
deprotection extended[134].
response the useThe
of the
probe in real water samples and prepared test strips. A novel selenium-based compound
probe identifies Hg 2+-induced thioacetal in the THF/H2O mixture, evolving deep blue flu-
probe, FSU, based on N-(phenylcarbamoselenoyl) furan-2-carboxamide, was presented for
orescence towards thegreen
optical fluorescence
and fluorimetricand greatly
detection strengthening
of Hg [135]. The sensor theis fluorescence
able to recognize inten-
Hg2+ in
sity. It presents an
theexcellent
DMSO/H2positive linear
O (95:5, v/v) relationship
system, indicating a with the concentration
fluorescence of Hglimit
burst with a detection 2+ at of
− 7
7.35 × 10 limit M, in
480 nm, with a detection aswhich
low as selenium
2.05 × behaves
10−7 M.as a magnet for
Moreover, themercury based on
researchers ICT.
extended
the use of the probe in real water samples and prepared test strips. A novel selenium-
based compound probe, FSU, based on N-(phenylcarbamoselenoyl) furan-2-carbox-
amide, was presented for the optical and fluorimetric detection of Hg [135]. The sensor is
able to recognize Hg2+ in the DMSO/H2O (95:5, v/v) system, indicating a fluorescence burst
7, x FOR PEER REVIEW 29 of 39
Molecules 2023, 28, 5689 28 of 38

Figure 22. The structures of The

Figure 22. probes ((a) isofLyso-HGP,
structures probes ((a) is(b) is DTCB,
Lyso-HGP, (b)and (c) is and
is DTCB, FSU).
(c) is FSU).

3.10.4. Fluorescent Probes to Detect Pb2+

3.10.4. Fluorescent Probes to Detect Pb2+
Pyrene derivatives are commonly encountered as chemosensors. In contrast to gen-
Pyrene derivatives arederivatives,
eral pyrene commonlypyrene encountered
derivatives as functionalized
chemosensors. In 2-position
at the contrast to bygen-
a one-step
eral pyrene derivatives, pyrene derivatives
iridium-catalyzed functionalized
reaction of B2pin2 at the 2-position
exhibit a prolonged fluorescenceby a one-step
lifetime, which facili-
iridium-catalyzed tates enhanced
reaction responseexhibit
of B2pin2 and improved sensitivity.
a prolonged Accordinglifetime,
fluorescence to this, V.which
Merz etfa-al. [136]
designed and synthesized a molecular
cilitates enhanced response and improved sensitivity. According sensor, sensor 3, composed of pyrene and
to this, V. Merz et al. tetraethy-
lene glycol together. The sensor could distinguish Pb2+ in ACN with a detection limit of
[136] designed and synthesized a molecular sensor, sensor 3, composed of pyrene and
6 × 10−7 M and has been successfully operated in water samples. Recently, porphyrins and
tetraethylene glycol together. The
phthalocyanines havesensor could distinguish
been frequently employed toPb
2+ in ACN with a detection
construct ratiometric metal ion sensors
limit of 6 × 10−7 Minand
viewhas
of been successfully
their tunable operated
photophysical in waterand
properties samples. Recently, porphy-
metal ion-binding characteristics.
2+ , showing
rins and phthalocyanines
For example, havethebeen frequentlyfraction
phthalocyanine employed(H2 Pc)tocould
construct ratiometric
selectively bind Pbmetal
ion sensors in viewfluorescence quenching
of their tunable and inhibitingproperties
photophysical the intramolecular
and metal process, thuschar-
FRETion-binding turning on
the fluorescence of the porphyrin fraction (ZnPor) [137].
acteristics. For example, the phthalocyanine fraction (H2Pc) could selectively bind Pb2+, In this way, 1 was constructed
as a novel phthalocyanine-porphyrin triplet [H2 Pc-β-(ZnPor)2 ] ratiometric fluorescent
showing fluorescence quenching and inhibiting the intramolecular FRET process, thus
probe [138]. The probe is utilized in the THF/MeOH (4:1, v/v) system to identify Pb2+ . It
turning on the fluorescence of the porphyrin
is possible to achieve detection of Pbfraction
2+ with(ZnPor)
a limit of [137]. In of
detection this
4.1 way, 1 was moni-
nM through
constructed as atoring
novelthephthalocyanine-porphyrin triplet [H Pc-β-(ZnPor) ]
fluorescence behaviors at 605 nm (ZnPor turn-on) and 700 nm (H2 Pc turn-off)
2 2 ratiometric
fluorescent probecorresponding
[138]. The probe is utilized
with increasing in the THF/MeOH
concentrations of Pb2+ under
(4:1, v/v)
Ex.420system
nm. The tostructures
iden- of
the probes are shown in Figure 23.
tify Pb . It is possible to achieve detection of Pb with a limit of detection of 4.1 nM
2+ 2+

through monitoring the fluorescence behaviors at 605 nm (ZnPor turn-on) and 700 nm
(H2Pc turn-off) corresponding with increasing concentrations of Pb2+ under Ex.420 nm.
The structures of the probes are shown in Figure 23.
Molecules 2023,28,
Molecules2023, 27,5689
x FOR PEER REVIEW 29 of
30 of 38
39

Figure23.
Figure 23. The
The structures
structuresof
ofprobes
probes((a)
((a)isissensor
sensor33and
and(b)
(b)isis1).
1).

Overall, researchers
Overall, researchers have have developed
developed numerous
numerous novel novel fluorophores
fluorophores or or recognition
recognition
groups
groupsin inrecent
recentyears
years that
that have
have broadened
broadened the the scope
scope ofof applications
applications for for fluorescent
fluorescent probeprobe
technology
technology in in heavy
heavy metal
metal detection
detection in in food.
food. Table 22 lists
lists the
the analytes,
analytes, detection
detection limits,
limits,
working
working solutions,
solutions, usage, and and references
referencesfor forall
allprobes
probespresented
presentedinin this
this review.
review. TheyTheyall
all exhibited
exhibited highhigh detection
detection capabilities
capabilities forfor various
various heavy
heavy metals
metals in food;
in food; however,
however, therethere
re-
remain
main some some challenges
challenges andand limitations.
limitations. ForFor example,
example, thethe heavy
heavy metals
metals identified
identified usingusing
the
the fluorescent probes reported so far almost present
fluorescent probes reported so far almost present only in the form of only in the form of inorganic ions.
ions. In In
practice,
practice, heavy metals are also found in organic form in food, such as mercuryHence,
heavy metals are also found in organic form in food, such as mercury [139]. [139].
itHence,
is still it
necessary to develop
is still necessary further fluorescent
to develop materialsmaterials
further fluorescent which enable which theenable
rapid,the
accurate,
rapid,
and nondestructive
accurate, detection detection
and nondestructive of organicofforms of heavy
organic forms metals.
of heavy Then, summarizing
metals. Then, summa- the
above
rizing discussion, it is clear that
the above discussion, it ismost
clearofthat
the available
most of the fluorescent
availableprobe-based
fluorescent assays work
probe-based
in solution
assays work media and depend
in solution mediaon andlarge laboratory
depend instruments,
on large laboratorysoinstruments,
developing so mobile instru-
developing
ments such as solid-loaded test kits or test strips for daily lives is
mobile instruments such as solid-loaded test kits or test strips for daily lives is urgentlyurgently needed, which
requires
needed, strong
which stability,
requires interference
strong stability, resistance, photobleaching
interference resistance, capability,
photobleaching simpler oper-
capabil-
ation
ity, simpler operation systems, etc. for the developed fluorescent probes. Althoughhave
systems, etc. for the developed fluorescent probes. Although few researchers few
integrated
researchersfluorescent probesfluorescent
have integrated with nanomaterials
probes with to overcome
nanomaterialsthe limitations
to overcome mentioned
the limi-
above,
tationsthe designedabove,
mentioned nanosensors
the designedmay exhibit nonspecific
nanosensors mayincorporations
exhibit nonspecific withinincorpora-
complex
food
tions within complex food matrices, leading to potential false approvals [140], whichtheir
matrices, leading to potential false approvals [140], which considerably restricts con-
wider
siderablypractical application
restricts their widerin thepractical
food industry. Consequently,
application in the food exploiting
industry. extra fluorescent
Consequently,
materials is required for improved probe utilization. This is challenging, yet we firmly
exploiting extra fluorescent materials is required for improved probe utilization. This is
acknowledge that this area of investigation is going to evolve rapidly via more research.
challenging, yet we firmly acknowledge that this area of investigation is going to evolve
We hope this review will facilitate developments in fluorescent probe detection of heavy
rapidly via more research. We hope this review will facilitate developments in fluorescent
metal ions in food and ultimately safeguard food safety and public health.
probe detection of heavy metal ions in food and ultimately safeguard food safety and
public health.
Table 2. Applications of fluorescent materials for heavy metal detection in food.

Probe Analytes
Table 2. Applications
LOD
of fluorescent materials for heavy metal detection Application
Working Solution
in food. Ref.
Probe
R1 Pb2+
Analytes 2.7LOD
× 10−9 M WorkingDMSO Solution Applicationseafood Ref.[40]
R1
REHBA Pb2+Pb2+ 2.7 ×0.73
10µM
−9 M DMSO
Tris-HCl (10 mM, pH = 7.0) seafoodwater [40][41]
REHBA3 Pb2+Hg2+ 0.73 µM Tris-HCl (10 mM, pH = 7.0) water [41]
15.80 nM MeOH/HEPES (1:9, v/v, pH = 7.4) cell imaging [42]
3
HL-CHO Hg2+Cr3+ MeOH/HEPES (1:9, v/v, pH =
15.80 nM cell imaging [42]
HL-CHO
p-RPT Cr3+Hg2+ 1.2 × 10−8 M 7.4)2 O (3:2, v/v)
THF/H water [43]
p-RPT
d114 Hg2+Hg2+ 1.2 ×8.6
10nMM
−8 THF/H 2O (3:2,
MeOH/H v/v)
2 O (1:1, v/v)
water
drinking water [43][44]
d114
FO511 HgHg2+
2+ 8.6 nM
92.7 nM MeOH/H 2 O (1:1, v/v)
HEPES (10 mM, pH = 7.2) drinking water
cell imaging [44][45]
FO511 Hg2+ 92.7 nM HEPES (10 mM, pH = 7.2) cell imaging [45]
Molecules 2023, 28, 5689 30 of 38

Table 2. Cont.

Probe Analytes LOD Working Solution Application Ref.

RBLY Hg2+ 0.34 µM EtOH/H2 O (1:5, v/v) water [46]
R6GH Pb2+ 0.02 µM THF/H2 O (1:1, v/v) seafood [47]
NA-RhB Pb2+ 0.00001 g·L−1 water [48]
Pb2+ 0.42 µM
FP EtOH/H2 O (99:1, v/v) tap water [49]
Cd2+ 0.53 µM
RhBQ Cr3+ 2.12 × 10−8 M ACN/H2 O (9:1, v/v) cell imaging [50]
RFC Cr3+ 0.0052 ppm MeOH/H2 O (99:1, v/v) cell imaging [51]
1O Cd2+ ACN [52]
Receptor Cr3+ 3.92 µM H2 O zebrafish [53]
C6 Cr3+ 13.3 µM ACN tap water [54]
Cr3+ 0.32 µM
PBD EtOH/H2 O (1:1, v/v) water, soil [55]
Hg2+ 1.93 µM
P Cr3+ 9.82 × 10−9 M DMF/H2 O (9:1, v/v) water [56]
SB2 Cr3+ 0.5 µM MeOH/H2 O (3:1, v/v) soil [57]
HMA Cr3+ 5.63 × 10−7 M DMSO/H2 O (9:1, v/v) water [58]
NHT Cr3+ 41 nM HEPES (0.2 mM, pH = 7.2) cell imaging [59]
L1 Cr3+ 1.12 × 10−7 M
ACN/H2 O (1:1, v/v) water [60]
L2 Cr3+ 7.73 × 10−7 M
1O Cd2+ 5.74 × 10−7 M THF water [62]
ACN/HEPES
PIS Cd2+ 2.10 × 10−8 M zebrafish [61]
(10 mM, pH = 7.4) (1:4, v/v)
PMPA Cd2+ 0.12 mM ACN water [63]
THF/Tris-HCl
DBTBH Pb2+ 4.49 × 10−8 M water [64]
(10 mM, 1 mM KI, pH = 7.4) (1:9, v/v)
BSBBT Pb2+ 2.23 × 10−6 M DMSO/H2 O (3:7, v/v) [65]
L Pb2+ 9× 10−7 M MeOH/Tris (1:1, v/v) water [66]
probe 1 Cd2+ 0.055 µM ACN water, bean sprouts [67]
QTPY Cd2+ 3.5 × 10−8 M DMF/H2 O (4:6, v/v) [68]
L Cd2+ 14.8 nM ACN/H2 O (8:2, v/v) water [69]
DDTQ Cd2+ 126 nM H2 O cell imaging [70]
Pb(II)-IIP Pb2+ 2.1 µg·L−1 H2 O water [71]
QMC Pb2+ 13 µM ACN/H2 O (1:1, v/v) milk, wine [72]
IL [HDQ] [P66614] Hg2+ 0.8 nM EtOH water, seafood [73]
DAC-Hg Hg2+ 5.0 nM PBS water, seafood, soil [74]
HCDC Hg2+ 0.3 nM HEPES (5 M, pH = 7.4) water [75]
L Hg2+ 5.15 nM bis-tris (10−2 M, pH = 7.0, 0.5% DMSO) water [76]
HEPES (20 mM, ACN/H2 O, 3:7, v/v,
1a Cd2+ 5.84 × 10−8 M [77]
pH = 7.0)
1 Cd2+ 0.114 µM THF/H2 O (1:1, v/v) [78]
C1-C3 Pb2+ 0.009–0.0015 ACN [79]
NIS Cd2+ 3.87 × 10−7 M HEPES (EtOH/H2 O = 9:1, v/v, pH = 7.4) zebrafish [80]
ACN/Tris-HCl
BPC Cd2+ 1.05 × 10−8 M water [81]
(3:2, v/v, pH = 7.4)
[PTZ-SB][Br] Cd2+ 3.8 × 10−7 M THF/H2 O (1:9, v/v) water [82]
IHL Cd2+ 0.4 × 10−10 M DMSO/H2 O (9:1, v/v) zebrafish [83]
Molecules 2023, 28, 5689 31 of 38

Table 2. Cont.

Probe Analytes LOD Working Solution Application Ref.

Hg2+ 7.6 × 10−6 M ACN/H2 O (1:1, v/v)
L1
Pb2+ 8.5 × 10−6 M ACN
[84]
Hg2+ 6.7 × 10−6 M ACN/H2 O (1:1, v/v)
L2
Pb2+ 2.5 × 10−6 M ACN
compound 1 Hg2+ 45.76 nM DMF/PBS (1:4, v/v, pH = 7.4) water [85]
L Cd2+ 0.03 ppm ACN/H2 O (4:1, v/v) [86]
NBDT Cr3+ 0.041 µM DMSO/H2 O (9:2, v/v) zebrafish [87]
CY Hg2+ 1.61 × 10−7 M DMSO/H2 O (7:3, v/v) water [88]
BTS Pb2+ 0.67 µM DMSO/H2 O (1:4, v/v) water [89]
ACN/HEPES water, soil, green
NBD-MPA Hg2+ 9.2 × 10−7 M [90]
(1:9, v/v) tea, seafood
PY 0.09 µM MeOH (pH = 7, PBS) water [91]
BPP Cd2+ 0.02 nM DMSO/H2 O (9:1, v/v) zebrafish [92]
ADMPA 29.3 nM DMF/H2 O (3:7, v/v) water [93]
3 Pb2+ 2.31 × 10−6 M ACN [94]
NT Cd2+ ACN [95]
H2 L Cd2+ 2.67 × 10−8 M MeOH food [96]
TND Pb2+ 4.7 nM ACN/H2 O (1:1, v/v) water [97]
probe 1 Pb2+ 1.65 nM ACN/EtOH/HEPES (1:1:2, v/v/v, pH = 7.0) water [98]
ACN/PBS sea bass, water,
TPA-TSC Hg2+ 0.14 nM [99]
(1:1, v/v, pH = 7.4) swordfish
TPE-Hg Hg2+ 7.548×10−7 M THF/HEPES (20 mM, pH = 7.3) (1:9, v/v) green tea, seafood [100]
TPE-M Hg2+ 4.16×10−6 M MeOH/PBS (20 mM, pH = 7.4) (3:7, v/v) green tea, seafood [101]
TPE-MC-P Pb2+ 0.27 µM THF/H2 O (1:9, v/v) water [102]
3 TS Hg2+ 1.03 × 10−8 M EtOH/H2 O (1:1, v/v) water, soil, seafood [103]
high-fructose corn
1.1 Hg2+ MeOH/H2 O [104]
syrup
NAPABTH Pb2+ 1.06 ppm DMSO [105]
CMN Cr3+ 0.68 µM MeOH [106]
probe 3 Cr6+ 1.15 µM ACN/HEPES (10 mM, pH = 7.4) (1:9, v/v) water [107]
NIDEA Hg2+ 46.7 nM HEPES (10 mM, pH = 7.4) water [108]
CM 1 19.25 nM H2 O water [109]
Cd2+
SAF 1.5 × 10−7 M ACN/H2 O (95:5, v/v) water [110]
PM Cd2+ 53 nM H2 O/dioxane (1/19, v/v) water, rice [111]
sensor C 2.3 × 10−9 M ACN water [112]
DNSC-CTV ACN [113]
Cr3+
HIMA 7.98 × 10−7 M DMF/H2 O (1:2, v/v) drinking water [114]
ANT-In 0.2 µM ACN/HEPES (7:3, v/v, pH = 7) drinking water [115]
Lyso-HGP 6.82 nM HEPES (10 mM, pH = 7.0, 1%DMSO) water [116]
DTCB Hg2+ 2.05 × 10−7 M THF/H2 O water [117]
FSU 7.35 × 10−7 M DMSO/H2 O (95:5, v/v) [118]
sensor 3 6 × 10−7 M ACN water [119]
Pb2+
1 4.1 nM THF/MeOH (4:1, v/v) [121]
Molecules 2023, 28, 5689 32 of 38

4. Conclusions and Outlook

In the past decades, heavy metal accumulation in food has emerged as a major prob-
lem contributing to food safety issues. Rapid and accurate determination of heavy metals
in food draws much more critical attention in safeguarding food safety. As an emerging
photochemical assay technique possessing the advantages of sensitivity, convenience, ac-
curacy, cost, and reliability, the fluorescence assay is becoming more and more practical
for determining hazards in the food industry in recent years, especially toxic heavy metals,
but only a few summarizing articles are available in this field. Hence, this review sys-
tematically presents the recent strides in the construction and potential applications of
novel fluorescent probes for food heavy metal detection in the past five years, which are
categorized according to fluorophores and newly emerging sensing cores. All endeavors
could contribute to broadening the prospects of fluorescent materials in the establishment
of rational assays for food safety.

Author Contributions: Investigation, methodology and writing original draft, L.L. and F.Y.; writing
review and editing, G.C. and Y.H.; supervision and project administration, L.H. and D.L. All authors
have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Natural Science Foundation of Fujian Province, China
(Grant number: 2021J01205) and the Special Fund Project of Marine Economic Development, Fujian
Province (2022, Grant number: FJHJF-L-2022-8).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data that support the findings of this study are available from the
corresponding author upon reasonable request.
Acknowledgments: We thank the Natural Science Foundation of Fujian Province, China (Grant
number: 2021J01205) and the Special Fund Project of Marine Economic Development, Fujian Province
(2022, Grant number: FJHJF-L-2022-8).
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: Not applicable.

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