Recent Progress in Metal–Organic Framework (MOF) Based Luminescent Chemodosimeters

Abstract

Metal–organic frameworks (MOFs), as a class of crystalline hybrid architectures, consist of metal ions and organic ligands and have displayed great potential in luminescent sensing applications due to their tunable structures and unique photophysical properties. Until now, many studies have been reported on the development of MOF-based luminescent sensors, which can be classified into two major categories: MOF chemosensors based on reversible host–guest interactions and MOF chemodosimeters based on the irreversible reactions between targets with a probe. In this review, we summarize the recently developed luminescent MOF-based chemodosimeters for various analytes, including H₂S, HClO, biothiols, fluoride ions, redox-active biomolecules, Hg²⁺, and CN⁻. In addition, some remaining challenges and future perspectives in this area are also discussed.

1. Introduction

Metal–organic frameworks (MOFs), constructed by metal ions (or clusters) with organic ligands, are a subclass of coordination polymers with highly crystalline structures [1,2]. In the past two decades, enormous progress has been made in the synthesis and application of MOFs [3,4,5]. Because of their remarkable structural features, such as high porosity and large surface area, as well as their exceptional physicochemical properties, MOFs possess versatile applications in gas storage and separation [6,7,8,9,10,11], heterogeneous catalysis [12,13,14,15], drug delivery and chemotherapy [16,17], and sensing [18,19]. As new types of promising functional materials, luminescent MOFs especially have great potential as alternative phosphors in lighting devices and luminescent sensors [20,21,22,23].

Due to the versatile building blocks of MOFs (inorganic ions and organic ligand molecules), as well as their structural diversity, the photoluminescence of MOFs can arise from a variety of possibilities [20]: (i) luminescence from organic linkers, which are normally extended π-conjugation systems with rigid structures, such as pyrene, anthracene, and their derivatives; (ii) metal-based emissions, e.g., MOFs with metal centers of lanthanoid; (iii) a metal–to–ligand charge transfer (MLCT), e.g., d¹⁰ Cu(I)- and Ag(I)-based MOFs; (iv) a ligand–to–metal charge transfer (LMCT), e.g., Zn(II)/Cd(II) and carboxylate ligand based MOFs; (v) antennae effects; and (vi) sensitization, e.g., MOFs with absorbing ligands and emitting lanthanoid ions (Figure 1). In the past, the competent luminescence features of MOFs have been extensively studied and exploited in fluorescence imaging and sensing applications [24]. These developed MOF-based luminescent probes can be classified into two types according to the recognition mechanism between the probe with the target analyte: (1) an MOF-based chemosensor, in which the analyte coordinates or interacts with the probe in a reversible manner, such as via physical/electrostatic interaction; (2) an MOF-based chemodosimeter, in which the target analyte can irreversibly react with a probe to yield a product that is chemically different from the starting probe via target-induced oxidation, hydrolysis, and nucleophilic processes.

MOF-based luminescent chemosensors have shown great potential in the detection of various analytes, including volatile organic compounds [25,26,27], ions (especially for metal cations) [28,29,30,31], gases [32,33,34,35], as well as for monitoring pH [36,37,38,39,40,41,42], humidity [43,44,45], and temperature [46,47,48]. Compared to the relatively well-developed fluorescent MOFs chemosensors, MOF-based chemodosimeters are expected to be more efficient in terms of selectivity, as they exploit the specific reactivities of certain target analytes [24]. Moreover, numerous MOF-based luminescent chemodosimeters can be afforded by introducing various recognition moieties for different analytes into building blocks. In the past several years, considerable effort has been expended in this field, and research interest is still growing. In spite of this interest, to date, the studies concerning MOF-based chemodosimeters have not yet been comprehensively addressed. To fill this gap, in the present review, we will make an effort to summarize recent progress in the development of MOF-based chemodosimeters. Moreover, the promising prospects and remaining challenges for future research in the field will also be discussed.

2. MOF-Based Luminescent Chemodosimeters for Sulfur Compounds

2.1. MOF-Based Chemodosimeters for H₂S

Hydrogen sulfide (H₂S), the smallest sulfhydryl compound, exists as a typical rotten egg smelling gas in the air or as a hydrosulfide ion while being dissolved in an aqueous solution under neutral pH conditions. Traditionally, H₂S was simply considered to be an environmentally toxic species. In recent years, H₂S has been discovered to be an essential biological molecule that can function as a cytoprotectant and gasotransmitter in organisms [49,50]. Moreover, the metabolism of H₂S is closely related to various physiological and pathological events in the human body [51,52]. In this context, the development of new methods for sensing H₂S and studying its biological roles has attracted tremendous attention [53,54,55]. Fluorescence technology is particularly promising for such purposes, as it enables monitoring of the target with superior temporal and spatial resolution [56,57,58,59], especially for in vivo applications. By exploiting its unique characteristics, such as strong nucleophilicity and ability to reduce potency, various small-molecule fluorescent probes have been developed for detecting and imaging H₂S. These probes can be mainly categorized into three types according to their sensing strategy: (i) sensors based on the H₂S-mediated reduction of an azide/nitro group to the amine [60,61,62,63]; (ii) sensors based on the H₂S-participated nucleophilic reaction [64,65,66,67]; and (iii) sensors based on the binding reaction between sulfide and Cu²⁺ [68,69]. By exploiting the similar sensing strategies and carefully employing post-synthetic modification approaches, a number of MOF-based fluorescent H₂S probes (

Table 1. List of MOF-based luminescent chemodosimeters for H₂S.

MOF Formula	λex/λem (nm)	Dynamic Range	LOD 1	RT 2	Media	Real Sampe	Ref.
Zr6O4(OH)4(BDC-N3)6	334/436	0–4 mM	117 μM	180 s	HEPES buffer (10 mM, pH 7.4)	Live cells	[71]
Zr6O4(OH)4(BDC-NO2)6	334/436	0–4 mM	188 μM	460 s	HEPES buffer (10 mM, pH 7.4)	--	[72]
Zn4O(OH)4(BDC-N3)3	395/455	0–0.5 mM	28.3 μM	90 s	HEPES ethanol buffer (10 mM, pH 7.4)	--	[73]
Ce6O4(OH)4(BDC-N3)6	334/429	0–3.5 mM	12.2 μM	760 s	HEPES buffer (10 mM, pH 7.4)	--	[74]
Ce6O4(OH)4(BDC-NO2)6	334/429	0–3.5 mM	34.8 μM	480 s	HEPES buffer (10 mM, pH 7.4)	--	[74]
Al(OH)(IPA-N3)	330/405	0–0.06 mM	2.65 μM	420 s	HEPES buffer (10 mM, pH 7.4)	Live cells	[75]
Zr6O4(OH)4((NDC-(NO2)2)6	390/474	0.1–0.7 mM	20 μM	50 min	HEPES buffer (10 mM, pH 7.4)	Live cells	[76]
Al(OH)(BDC-N3)	315/425	0.2–1.6 μM	90.47 nM	60 s	HEPES buffer (10 mM, pH 7.4)	Live cells	[77]
Al3O4(OH)4(BDC-(NO2)2)6	345/527	0.1–0.6 mM	14.14 μM	40 min	HEPES buffer (10 mM, pH 7.4)	Live cells	[78]
Al3(O)(OH)(BDC-N3)3	343/460, 565	0.1–120 μM	100 nM	--	Hank’s balanced salt solution	Cell sample	[79]
Al(OH)(BDC-NO2)/poly(vinylidene fluoride)	396/466	0–0.1 mM	92.31 nM	--	PVDF membrane	Lake water	[80]
Cu(TCPP)[AlOH]2	419/602, 650	0–10 μM	16 nM	instant	BBS buffer (20 mM, pH 7.4)	Live cells	[81]
CuO@TO@UiO-66	510/~560	0–100 μM	0.51 μM	instant	Tris-HCl butter (20 mM, pH 7.4)	Live cells	[82]
Eu3+/Cu2+@UiO-66-(COOH)2	305/393, 615	0–625 μM	5.45 μM	30 s	HEPES buffer (10 mM, pH 7.4)	--	[83]
Eu3+/Ag+@UiO-66-(COOH)2	305/615	0–2.5 mM	23.53 μM	30 s	HEPES buffer (10 mM, pH 7.4)	Serum	[84]
Tb3+@[Cu(CPOC)2]	280/390, 544	0–1.6 mM	13.25 μM	2 min	HEPES buffer (10 mM, pH 7.4)	--	[85]
UiO-66-CH = CH2 Zr6O4(OH)4(BDC-CH = CH2)6	328/382	0–0.05 mM	6.46 μM	10 s	HEPES buffer (10 mM, pH 7.4)	Live cells	[86]
FeIII-MIL-88-NH2	333/~440	60–100 μM	10 μM	5 min	Aqueous solution	--	[87]

¹ LOD means limit of detection. ² RT means reaction time.

) were successfully constructed in the last few years [70].

2.1.1. Based on the H₂S-Mediated Reduction of Azide/Nitro Group to Amine

Ghosh et al. first reported a Zr-based MOF, Zr₆O₄(OH)₄(BDC-N₃)₆ (UiO-66@N₃), bearing an azide group for sensing H₂S [71]. The MOF-based chemodosimeter UiO-66@N₃ was prepared via post modification of the amine functionalized UiO-66@NH₂ using an azidation agent. UiO-66@N₃ is highly stable in an aqueous solution and fluoresces very weakly due to the presence of an electron-deficient azide group (Figure 2). Treating UiO-66@N₃ with Na₂S in an HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) aqueous buffer (10 mM, pH 7.4) creates a strong emission (16-fold enhancement), which can be ascribed to the target-mediated reduction of azide to amine, which produces the luminescent UiO-66@NH₂. This conversion process is characterized by FTIR (Fourier Transform infrared spectroscopy) and NMR (Nuclear Magnetic Resonance Spectroscopy) studies. UiO-66@N₃ can respond rapidly to H₂S (less than 180 s) with high selectivity over other interferences, including most abundant biothiols (Cys and GSH). Moreover, UiO-66@N₃ also displays low cell viability and has been applied to live cell imaging studies. The same research group subsequently prepared a nitro-functionalized Zr-MOF (UiO-66@NO₂) for the fluorescence turn-on detection of H₂S, in which UiO-66@NO₂ can be facilely obtained in a single synthetic step by using 2-nitroterephthalic acid as the ligand [72]. Incorporation of the azide/nitro group onto other MOFs scaffolds has afforded a variety of luminescent H₂S chemodosimeters. Qian et al. reported an azide-appended Zn-MOF for the fluorescent turn-on detection of H₂S [73]. In a HEPES ethanol buffer, the probe displayed excellent selectivity and a rapid response time for H₂S. By directly reacting the cerium(IV) nitrate with an azide/nitro-substituted 1,4-benzenedicarboxylate (BDC), Biswas et al. synthesized two Ce-MOFs (Ce-UiO-66@N₃, Ce-UiO-66@NO₂) for sensing H₂S [74]. Since then, the Biswas group has developed a number of reaction-based luminescent H₂S sensors, including Al(OH)(IPA-N₃) [75], Zr₆O₄(OH)₄((NDC-(NO₂)₂)₆ [76], Al(OH)(BDC-N₃) [77], and Zr₆O₄(OH)₄(BDC-(NO₂)₂)₆ [78]. Further, Al(OH)(BDC-N₃) was also employed as a turn-off fluorimetric sensor for detecting Fe(III) in an aqueous solution [77].

Canivet et al. reported an Al-MOF, Al₃(O)(OH)(BDC-N₃)₃ (Al-MIL-101-N₃, Figure 3a) based sensing system for H₂S [79]. It is worth noting that the use of a femtosecond (fs)-pulse laser excitation can significantly improve the emission features as well as the analytical performances of this MOF-based luminescent assay. All these investigated BDC-based MOFs (Al-MIL-101-NH₂, In-MIL-68-NH₂, and Zr-UiO-66-NH₂) displayed characteristic emissions at about 460 nm (Figure 3b) under UV-lamp excitation at 343 nm. While under fs-pulse laser excitation, Al-MIL-101-NH₂ revealed another predominent emission band centered at 565 nm, which may have resulted from an increase of the luminescence center in the electronic excited state and the redistribution of the photoexcited charge carriers (Figure 3c,d). The spectral behaviors of Al-MIL-101-N₃ for H₂S were studied in DMSO (dimethyl sulfoxide) as well as in HBSS (Hank’s balanced salt solution). In the biological media of HBSS, Al-MIL-101-N₃ displayed a wide dynamic range of 0.1–120 μM and a low LOD of 100 nM for H₂S (Figure 3e,f). Moreover, Al-MIL-101-N₃ was applied to detect sulfide from an exogenous small molecule releaser (GYY4137) and endogenous H₂S produced by 3T3L1 cells (Figure 3g,h).

By integrating Al-MOF (Al(OH)(BDC-NO₂), Al-MIL-53-NO₂), and poly(vinylidene fluoride) (PVDF), Qian et al. developed a novel MMM (MOF-polymer mixed-matrix membrane) for the fluorescence turn-on detection of H₂S [80]. The Al-MIL-53-NO₂@PVDF MMM can be readily prepared with a high loading of the MOF probes (70 wt%), following the procedures as depicted in Figure 4a. The obtained Al-MIL-53-NO₂ MMM is mechanically robust and flexible and can be easily handled. The Al-MIL-53-NO₂ MMM can be effectively applied to the flow-through detection of H₂S, which exhibited remarkably high sensitivity with an LOD of 92.31 nM (Figure 4b,c).

Furthermore, the constructed Al-MIL-53-NO₂ MMM was also used to detect H₂S in real water samples.

2.1.2. Based on the Binding Reaction between S²⁻ and Cu²⁺

Tang et al. firstly reported a Cu(II)-metalated MOF, Cu(TCPP)[AlOH]₂ (TCPP: meso-tetrakis(4-carboxylphenyl)porphyrin), for luminescent sensing of H₂S [81]. Cu(TCPP)[AlOH]₂ was obtained via Cu(II) metalation of the porphyrin ring-contained parent MOF TCPP[AlOH]₂(DMF)₃(H₂O)₂. The paramagnetic Cu(II) ions can quench the ligand-based (porphyrin) fluorescence of Cu(TCPP)[AlOH]₂. Upon the addition of H₂S, the Cu(II) ion can be taken from the porphyrin center via the formation of a CuS precipitate, thereby leading to the recovery of porphyrin-based emissions in the MOF system (Figure 5a). The fluorescence response of Cu(TCPP)[AlOH]₂ to H₂S can occur instantaneously with high sensitivity (LOD: 16 nM) and excellent selectivity as other analytes did not generate any fluorescence enhancement. Luminescence imaging studies also demonstrated that Cu(TCPP)[AlOH]₂ can be employed for monitoring both exogenous and endogenic H₂S in liver hepatocellular (HepG2) cells (Figure 5b). The Tang group recently developed a CuO NPs functionalized NMOF (Nanoscale metal–organic frameworks) hybrid nanoprobe, CuO@TO@UiO-66, for the sensing and imaging of H₂S [82]. Due to the energy transfer process from TO@UiO-66 to CuO NPs, the nanoprobe is weakly emissive. Sulfide can react with CuO to release the luminescent TO@UiO-66, thereby achieving a sensitive turn-on fluorescence response to H₂S.

Qian et al. prepared a nano MOF Eu³⁺/Cu²⁺@UiO-66-(COOH)₂ system for the ratiometric luminescent sensing of H₂S by the post-modification of UiO-66-(COOH)₂ with Eu³⁺ and Cu²⁺ ions [83]. This MOF system displayed two distinct emissions, a sharp Eu³⁺ emission at 615 nm and a broad ligand-based emission at 393 nm. Due to the decreased antenna efficiency of the H₄btec ligands to Eu³⁺ in the presence of Cu²⁺, Eu³⁺/Cu²⁺@UiO-66-(COOH)₂ exhibited a weak Eu³⁺ emission and a relatively enhanced ligand-based emission. While the target sulfide can effectively snatch the copper ion from the MOF probe and result in a significant enhancement in the fluorescence intensity ratio (I₆₁₅/I₃₉₃), thus achieving a ratiometric fluorescence response for H₂S (Figure 6). Other advantageous features of this MOF sensor include excellent compatibility with aqueous media and instant response. However, it should be noted that other sulfhydryl compounds (i.e., GSH, Hcy, and Cys) also generated a certain degree of fluorescence response, which may be ascribed to the moderate binding affinity of H4btec to Cu²⁺, and these interferences also competitively bind to Cu²⁺. The same research group consequently developed a fluorescent MOF-based logic platform Eu³⁺/Ag⁺@UiO-66-(COOH)₂ for H₂S detection [84].

Yang et al. reported a luminescent composite Tb³⁺@Cu-MOF for the turn-on ratiometric sensing of H₂S [85]. The synthesis process for Tb³⁺@Cu-MOF and the sensing mechanism for H₂S are shown in Figure 7a. The Cu-MOF, [Cu(CPOC)₂] was firstly prepared by reacting copper salt with an organic ligand (CPOC: 5-(4′-carboxyphenoxy) nicotinic acid). SC-XRD (single crystal X-ray diffraction) analysis indicated that [Cu(CPOC)₂] belongs to the monoclinic system (P2₁/c), with a half crystallographically independent metal center and one ligand per asymmetric unit (Figure 7b). The probe Tb³⁺@Cu-MOF can be readily obtained via post-grafting modification with Tb³⁺. [Cu(CPOC)₂] displayed an emission band at about 390 nm. Tb³⁺@Cu-MOF showed additional emissions of the Tb³⁺ ion (at 489, 544, 585, and 620 nm) but with relatively weak intensities because the Cu²⁺ with an unsaturated electronic state (3d⁹) has a tendency to gain electrons and thus quench the fluorescence. With the addtion of sulfide, Cu²⁺ can be bounded and, as a consequence its quenching effect, can be hindered, leading to a significant and selective increase in the characteristic emissions of Tb³⁺ (Figure 7c). Noticeably, the Tb³⁺@Cu-MOF well retained its crystalline structure after being incubated with Na₂S.

2.1.3. Other MOF-Based Chemodosimeters for H₂S

Cui et al. designed a vinyl-functionalized Zr-MOF (UiO-66-CH = CH₂) for detecting H₂S by using 2-vinylterephthalic acid as the linker ligand [86]. UiO-66-CH = CH₂ showed a turn-off fluorescence response toward H₂S with high sensitivity and selectivity. This probe also featured low toxicity and good water stability, but the sensing mechanism is not discussed in this study. Wang et al. reported a novel turn-on fluorescent assay for H₂S based on the target-mediated collapse of an MOF structure (Fe₃O(OH₂)₃(BDC-NH₂)₃, Fe^III-MIL-88-NH₂) (Figure 8) [87]. Due to the paramagnetic nature of Fe(III), Fe^III-MIL-88-NH₂ is non-emissive. Mixing the Fe^III-MIL-88-NH₂ suspension with a NaHS solution can lead to the breakdown of the MOFs and a release of the luminescent ligand of 2-aminoterephthalic acid.

2.2. MOF-Based Chemodosimeters for Biothiols

Biothiols such as Cys (cysteine), Hcy (homocysteine), and GSH (glutathione) play vital roles in various physiological and pathological processes [88,89,90,91]. During the past decade, a huge number of fluorescent probes have been developed for sensing and imaging biothiols by exploiting the specific reactivities of sulfhydryl group and/or amino group [92,93,94,95,96,97,98], including nucleophilic addition to electron-deficient unsaturated bonds, conjugate addition−cyclization reaction, cleavage of sulfonamide and sulfonate ester, cleavage of disulfide, and displacement of coordination to the metal complex. MOF-based Chemodosimeters for fluorescent sensing biothiols have emerged in the last two years.

Ghosh et al. reported a turn-on fluorescent probe, UiO-66-DNS, for selective sensing of biothiols [99]. UiO-66-DNS was prepared by post-grafting 2,4-dinitrosulfonyl moiety (DNS) to the chemically stable UiO-66-NH₂ MOF. UiO-66-DNS exhibited weak fluorescence due to the PET (photoinduced electron transfer) from the ligand of 2-aminoterephthalic acid to the highly electron-withdrawing functional group of DNP (Figure 9a). After the addition of Cys to a UiO-66-DNS dispersed water solution (Figure 9b), a significant enhancement (ca. ∼48-fold) in luminescent intensity at 432 nm was obtained, which can be ascribed to the thiol-mediated cleavage of the DNS moiety and the release of UiO-66-NH₂. Compared with Cys, UiO-66-DNS displayed slower response toward GSH because of its intrinsic bulkier feature for diffusing and interacting with the probe. Other amino acids did not generate any obvious enhancement in the emission intensity of the probe (Figure 9c), which demonstrated that the UiO-66-DNS is highly specific to biothiol.

Wu et al. developed a novel aldehyde-functionalized MOF, Cd–PPCA (Figure 10a), for selective sensing of Hcy [100]. The Cd–PPCA consisted of a Cd(II) metal center and two types of ligands, H₃tca (4,4′,4″-tricarboxyltriphenylamine) and ppca (1H-pyrrolo-[2,3-b] pyridine-2-carbaldehyde). XRD (X-ray diffraction) results indicated that Cd–PPCA crystallized in the orthorhombic space group Pbnm with a = 25.500(5), b = 20.600(4), c = 13.700(3) Å (Figure 10b). Each unit building of trinuclear [Cd₃(COO)₈] contained one ppca ligand, with a nitrogen atom to coordinate with Cd and a desired aldehyde functional group for the specific recognition of the target Hcy. Suspended in a HEPES (pH = 7.4) buffer solution, Cd–PPCA showed a weakened fluorescence emission at about 450 nm compared with similar MOFs comprised of H₃tca ligands and Cd²⁺ nods, which can be attributed to the PET from the triphenylamine groups to the electron withdrawing aldehyde moieties of the ppca ligand. With the addition of Hcy, the emission intensity of the assay showed a significant enhancement (Figure 10c), which can be ascribed to the selective reaction of the aldehyde moiety with Hcy and thus the inhibition of the PET process. This fluorescent response was also observed to be very fast (60 s) and sensitive (LOD: 40 nM). Moreover, the probe Cd–PPCA exhibited excellent specificity for Hcy over other species, including Cys (Figure 10d).

Wang and Zhang et al. developed a novel Zr-MOF based fluorescent PET switch/sensor, UiO-68-An/Ma [101]. The probe contains two kinds of ligands, one embedded with the anthracene unit serving as the luminophore and the other appended with a maleimide moiety as the PET acceptor (Figure 11a). The multivariate UiO-68-An/Ma favors a pseudo-PET process and only shows very weak fluorescence with an absolute PLQY (photoluminescence quantum yield) of 1.1%. Notably, the fluorescence behavior of UiO-68-An/Ma can be tuned by altering the acceptor moiety and thus the PET process. The authors firstly confirmed the tunable fluorescence response of UiO-68-An/Ma via a reversible D–A reaction with 3-furanmethanol. Furthermore, UiO-68-An/Ma was applied for sensing biothiols based on the well-established maleimide–thiol addition reaction. As a solid-state fluorescent turn-on sensor, UiO-68-An/Ma can sensitively response to biothiols (Cys, Hcy, and GSH) as low as 50 µM (Figure 11b).

With the in-situ encapsulation of rhodamine B (RhB) into Cu-BTC, Gao and Huang et al. reported a turn-on fluorescent assay (RhB@Cu-BTC MOFs) for sensing Cys [102]. The fluorescence of RhB@Cu-BTC was very weak because the embedded RhB was adjacent to the paramagnetic copper center. In the presence of Cys, the Cu-BTC framework collapsed, which resulted the release of RhB and thus a turn-on fluorescence response (Figure 12).

The MOF based fluorescent probe has also been exploited for sensing sulfur dioxide (SO₂) or sulfite/bisulfite, another kind of important sulfur-containing specie on both biological and environmental aspects. Ghosh et al. constructed a MOF based luminescent probe, NH₂-MIL-68(In)@CHO, for the monitoring of bisulfite [103]. The probe was prepared by the post synthetic approach via condensation of NH₂-MIL-68(In) (In(OH)(bdc-NH₂)) with glyoxal (Figure 13). The introduced aldehyde moiety can react with bisulfite to generate an OH group, which is available to form an intramolecular hydrogen bond and thus resulted in the inhibition of the C = N isomerization and the recovery of the fuorescence of the probe. Cui and Qian et al. prepared a Eu-BDC-NH₂ film on the UiO-66-NH₂ modified glass through an in situ secondary growth and successfully applied this functional film for sensing gaseous sulfur dioxide [104].

3. MOF-Based Chemodosimeters for Other Redox-Active Biomolecules

3.1. MOF-Based Chemodosimeters for HClO

Hypochlorous acid (HClO) is an important chemical reagent with wide application in various areas of organic synthesis, the cosmetics industry, food service, water treatment, etc. In living organisms, HClO is a kind of essential reactive oxygen species (ROS), which is normally produced in phagosomes via the reaction between hydrogen peroxide and chloride ions catalyzed by myeloperoxidase [105]. As a powerful oxidizer, the endogenous HClO can act as effective microbicidal agent when the host is being invaded by microbials [106]. On ther hand, HClO can also react with functioning biomolecules, such as proteins, nucleic acid, and fatty acids, which would produce adverse effects for organisms and correlate to numerous human diseases, such as kidney disease, cardiovascular diseases, and even cancers [107]. Therefore, the development of reliable analytical methods for monitoring HClO has attracted a great deal of attention [108,109]. Based on the unique characteristics of HClO, acting as both a potent oxidant and a good chlorination agent, various reaction-based organic fluorescent probes has been reported for selective sensing of HClO [110,111,112,113,114,115,116,117]. Until now, several examples of MOF-based chemodosimeters for luminescent detection of HClO have been presented.

Ma and Wang et al. developed the first MOF-based chemodosimetric probe for sensing HClO [118]. The designing strategy for the probe, UiO-Eu-L1 (L1: dimethyl 4-(carbaldehyde oxime) pyridine-2,6-dicarboxylate), is depicted in Figure 14. Uio-Eu-L1 was obtained by successively treating the Zr-MOF UiO-67 (Zr₆O₄(OH)₄(BPDC)₆) with europium ions and the functional ligand L1. Due to the efficient C = N isomerization-induced fluorescence quenching, UiO-Eu-L1 displayed very weak red emissions derived from europium ions. In the presence of HClO, the hydroxylamine moiety can be converted to aldehyde, which, in turn, leads to the inhibition of the C = N isomerization and thus the turn-on fluorescence response of the probe system. Ascribed to the long-lived phosphorescence of the Uio-Eu based MOF, this luminescent assay can efficiently eliminate the background signals and auto-fluorescence effects by the use of time-gated measurements. Uio-Eu-L1 also exhibited high sensitivity for HClO with a dynamic range of 0.1–5 μM and a detection limit of 16 nM.

Gu et al. presented a novel luminophore integrated MOF system, AF@MOF-801, for specific detection of HClO [119]. The composite AF@MOF-801 can be readily prepared via a one-step process by using 5-aminofluorescein (AF) as a co-reactant in the synthesis of MOF-801 (Figure 15a). AF can serve as a sensitive turn-off fluorescent HClO probe, as HClO can react with AF to produce chlorinated products. However, other coexistent biological molecules (such as dopamine, DA) also can lead to the similar fluorescent changes of AF. In the constructed sensory platform of AF@MOF-801, AF can be confined in the cages of the framework and the target HClO can diffuse into the framework to react with the probe AF, while the ultra-small aperture can block the entry of large-sized interferents. Due to this size-selective effect, AF@MOF-801 displayed excellent specificity for HClO. Only ClO⁻ produced the significant luminescence response of AF@MOF-801 (Figure 15b), while both ClO⁻ and DA generated strong fluorescence quenching for the free AF probe (Figure 15c). The feasibility of AF@MOF-801 for monitoring intracellular HClO was also demonstrated by MTT assay and flow cytometry analysis (FCA), as well as confocal laser scanning microscopy (CLSM) measurements (Figure 15d).

Chen et al. constructed a fluorophores@MOF (F1-Rubpy@ZnMOF74) nanocomposite-based ratiometric fluorescent probe for HClO by simultaneously encapsulating two fluorophores, fluorescein o-acrylate (F1) and tris(2,2′-bipyridyl)-dichroruthe-nium(II) hexahydrate (Rubpy), into ZnMOF74 [120]. F1-Rubpy@ZnMOF74 displayed two distinct emissions at 512 nm and 600 nm, corresponding to F1 and Rubpy, respectively. In the presence of HClO, the fluorescence of the target-responsive fluorophore F1 can be quenched, while the reference signal that originated from Rubpy remained unchanged, thus achieving a ratiometric response for HClO. In an aqueous HEPES buffer (pH = 7.5) solution, the fluorescence intensity ratio (I₅₁₂/I₆₀₀) of the F1-Rubpy@ZnMOF74 was found to be linearly correlated with the concentration of ClO⁻ with a dynamic range of 3.6 nM-100 μM.

3.2. MOF-Based Chemodosimeters for Ascorbic Acid

Chen and Qian et. al. developed a Ce-MOF sensor ZJU-136-Ce, (Me₂NH₂)_0.6{[Ce^IV(TPTC)]_0.4-[Ce^III(TPTC)]_0.6}(H₂O)₂(H₄TPTC = 1,1′:4′,1″-terphenyl-2′,4,4″,5′-tetracarboxylic acid) for sensing ascorbic acid (AA) [121]. Ce^IV in the probe ZJU-136-Ce can react with the AA to generate Ce^III and oxidized AA (DHA, dehydroascorbic acid). ZJU-136-Ce displays a luminescence band at 380 nm with a lifetime of 0.84 ns, which corresponds to the emissions of the Ce ion (Figure 16a). After reacting with AA, the probe system shows an increased emission band at about 400 nm (Figure 16b), which corresponds to the emission of the ligand. This fluorescence spectral response can be ascribed to the enhanced conjugation effect of the oxidized product DHA and thus the inhabited PET process from the TPTC ligand to the Ce ion. Subsequently, by introducing the Eu ions into the MOFs ZJU-136-Ce, the Qian group constructed a dual-emissive MOFs, ZJU-136-Ce_1−xEu_x (x = 0.24, 0.36), which can serve as an efficient ratiometric probe for monitoring AA [122]. The same research group also reported a new Zn-MOF, ZnL(H₂O) (ZJU-137, H₂L = 4,4′-(1H-pyrazole-1,3-diyl)dibenzoic acid, for the fluorescence “turn-off” detection of AA [123].

3.3. MOF-Based Chemodosimeter for 5-Hydroxytryptamine

Shi and Cheng et al. presented a Ln-MOF, Ln-MOF 1: {[Eu(TDA)(H₂BTEC)_0.5(H₂O)₃]·H₂O}_n (H₂TDA = thiazolidine 2,4-dicaboxylic acid, H₄btec = 1,2,4,5-benzenetetracarboxylic acid), for sensing 5-hydroxytryptamine (HT) and 5-hydroxyindole-3-acetic acid (HIAA), which was synthesized by reacting Eu³⁺ with mixed ligands of H₂TDA and H₄BTEC [124]. Ln-MOF 1 is crystallized in the monoclinic space group P2₁/c, in which each Eu³⁺ ion is nine-coordinates in a spherical capped square antiprism coordination geometry (Figure 17a). Due to the conjugated π system and the pronounced antenna effect of the ligand BTEC, Ln-MOF 1 displays intense characteristic emissions of the Eu³⁺ emitter with a maximum peak located at 616 nm, which is ascribed to the ⁵D₀→⁷F₂ transition of Eu³⁺ ion. In the presence of HT or HIAA, the luminescence of the Ln-MOF 1 can be effectively quenched (Figure 17b,c). This process was attributed to the competitive absorption of excitation light by the analyte and the ligand. Ln-MOF 1 displayed several favorable features for HT and HIAA sensing, including high stability over a wide pH range and long-term storage, excellent sensitivity, and fast response time.

3.4. MOF-Based Chemodosimeter for H₂O₂

The hydrogen peroxide (H₂O₂) mediated conversion of arylboronates to phenols has been widely exploited for the development of fluorescent H₂O₂ probes [125]. On the basis of this unique chemical reaction, Biswas et al. developed a Zr-MOF based probe, Zr-UiO-66-B(OH)₂, for sensing H₂O₂ [126]. Zr-UiO-66-B(OH)₂, which can be can be easily prepared by reacting ZrOCl₂·8H₂O with the linker of BDC-B(OH)₂ (2-boronobenzene-1,4-dicarboxylic acid) (Figure 18). Zr-UiO-66-B(OH)₂ can act as a sensitive and selective off−on luminescent chemodosimeter for H₂O₂ with a 4-fold increment in the fluorescence intensity upon the addition of an excess amount of the target. Moreover, the probe Zr-UiO-66-B(OH)₂ was successfully applied to image H₂O₂ in MDAMB-231 cells.

4. MOF-Based Chemodosimeters for Ions

4.1. MOF-Based Chemodosimeters for Fluoride Ions

The fluoride ion, F⁻, as a typical hard Lewis base with the smallest ionic radius and highest charge density, has attracted much interest due to its association with various biological, medical, and technological processes. Commonly, fluoride is considered to be a critical component for preventing dental caries as fluoride can promote the formation of enamel-strengthening fluorapatite [127,128,129]. However, the over intake of fluoride can lead to excess mineralization within oganisms and cause gastric and kidney problems. Various analytical techniques have been developed for sensing fluoride [130], including the well-established electrochemical method [131,132], chromatography [133,134], and colorimetric and fluorogenic assays [135]. In the past decades, numerous fluorescent probes have been developed for fluoride based on different fluoride-participated processes, such as fluoride-induced Si−O or Si−C bond cleavage, H−F hydrogen bonding formation, and Lewis acid−base interactions [136,137,138]. By exploiting these special reactivities of fluoride, several MOF-based luminesscent probes have recently been developed for its detection [139,140].

Yin et al. reported a reaction-based MOF probe (Eu-bop, Eu₂(isp)₃(H₂O)₂) for fluoride ions [141]. Eu-bop was prepared by using Eu³⁺ as the metal node and 5-bop (5-boronoisophthalic acid) as the ligand that contains a recognition moiety of a boric acid group for the target F⁻. The substituted boric acid group also can tune the electronic structure of the ligand and resulted in an incomplete energy transfer from the ligand to Eu³⁺ emitter in the probe Eu-bop. Therefore, the Eu-bop displayed two emission bands: 366 nm, corresponding to the ligand of 5-bop; and 570–750 nm, corresponding to Eu³⁺. Upon the addition of fluoride ions, the emission intensity at 366 nm was significant increased with a concomitant decrease in emissions at 625 nm (Figure 19a). The fluorescence response can be ascribed to the OH/F exchange reaction on the boron atom, which changed the hybridization state of boron from sp² (−B(OH)₂) to sp³ (−BF₃), and thus disrupted the p_π−π conjugation of the 5-bop and the decreased intersystem crossing efficiency (Figure 19b), as well as the antenna effect of the ligand. The fluorescence intensity ratio (I₆₂₅/I₃₆₆) of the probe system was found to vary linearly with the concentration of fluoride in a range of 4–80 μM. The probe was also applied to detect fluoride in real samples of river and underground water.

Recently, Stylianou et al. developed a luminescent lanthanide MOF, ([Eu(tctb)(H₂O)]·2DMF), referred to as SION-105 for the recognition of fluoride ion [142]. SION-105 consisted of tris (p-carboxylic acid) tridurylborane ligand (tctb³⁻) and an Eu^III metal center. The ligand tctb³⁻ contains a three-coordinate B acting as the recognition site for F⁻ and the surrounding duryl groups offering size-selective steric protection from other interferences (Figure 20a). SION-105 displayed a strong characteristic Eu^III luminescent emission due to the efficient antenna effect of the ligand tctb³⁻ (Figure 20d). Upon the addition of F⁻, the emissions of the probe can be quenched due to the specific interaction of F⁻ with the B Lewis acid site. A linear luminescence quenching response of SION-105 towards the F⁻ ion was observed in a range of 0.5 to 2.0 ppm (Figure 20b). A Stern−Volmer plot of quenching with the F⁻ concentration indicates the occurrence of both static and dynamic quenching (Figure 20c).

4.2. MOF-Based Chemodosimeter for Hg²⁺

Mercury is one of the most toxic heavy metals in the environment. In aqueous media, mercury can be transformed into methylmercury, a powerful neurotoxin, which can be accumulated and ingested by humans through the food chain [143,144,145]. In the human body, methylmercury can lead to serious symptoms, such as cognitive and motor disorders, neurological impairments, brain damage, and even death [146,147,148]. These environmental and biological problems have prompted the rapid development of techniques for sensing mercury [149,150,151,152,153]. Until present, many reaction-based fluorescent probes for Hg²⁺ have been developed based on various Hg²⁺-induced chemical processes [154,155,156], such as desulfation or deselenization processes, desulfation and cyclization processes, thiol elimination process, and the oxymercuration−elimination of vinyl/alkyne ether. Recently, Ghosh reported a MOF probe (UiO-66@Butyne) for the reaction-based detection of Hg²⁺ [157]. UiO-66@Butyne was prepared from Zr ion and a ligand of 2,5-bis (but-3-yn-1-yloxy) terephthalic acid, which contained a butyne moiety acting as the recognition site for Hg²⁺ (Figure 21a). The prepared UiO-66@Butyne retained the crystalline structure of MOF UiO-66 and showed a strong green emission (λ_em,max = 537 nm). Addition of Hg²⁺ to the aqueous solution of UiO-66@Butyne can result in fluorescent quenching of the system (Figure 21b), which can be attributed to the target-induced conversion of UiO-66@Butyne to the less fluorescent product of UiO-66@OH through the process of oxymercuration−elimination of ethynyl ether. As this MOF-based chemodosimeter exploited the specific reactivity of the target, UiO-66@OH exhibited excellent selectivity for Hg²⁺.

4.3. MOF-Based Chemodosimeter for CN⁻

The cyanide ion is an extremely poisonous chemical with widespread applications in industries such as metal mining, electroplating, and plastic and fertilizer manufacturing [158,159]. Various methods have been developed for the quantitative analysis of CN⁻, including the titration method, electrochemical assays [160], chromatography [161], as well as the colorimetric and fluorogenic method [162]. Among these methods, the design and use of fluorescent probes for sensing CN⁻ have received considerable attention [163,164,165]. The chemososimeters for CN⁻ monitoring are normally associated, with several typical chemical reactions, including the cyanohydrin forming process, additions to the dicyano-vinyl group, michael addition, and indolium or pyridinium addition reactions. Recently, based on the specific addtion reaction of CN⁻ dicyano-vinyl group, Ghosh developed a Zeolitic imidazolate framework, M-ZIF-90 ([Zn(C₈H₆N₄O₂)]_n), for fluorescence sensing CN⁻ [166]. M-ZIF-90 was prepared by incorporating the recognition moiety of dicyano-vinyl onto the aldehyde-appended ZIF-90 via post-synthetic modification (Figure 22). In the H₂O/DMSO (1:1) mixture, M-ZIF-90 displayed a turn-off fluorescence response towards CN⁻ based on the nucleophilic addition of CN⁻ to the dicyano-vinyl group, which would interrupt the π-conjugation of the probe and thus result in significant fluorescence change.

5. Conclusions

In recent years, the design, synthesis, and application of MOFs have attracted an ever-increasing interest of researchers in the fields of chemistry, physics, materials, and engineering. The porous and crystalline nature, versatile selections for metal nodes and organic linkers, and tunable structures also endow MOFs with unique characteristics for sensing applications. In this review, we summarized recently developed MOF-based luminescent chemodosimeters. These reaction-based luminescent probes inherit the robust structural features of MOFs (e.g., large surface area, high porosity, and good thermal and chemical stability) and also exhibit excellent selectivity as they exploit the specific reactivities of the target analyte. Several strategies have been involved in the development of MOF-based chemodosimeters: (i) installing the recognition moiety onto the ligand via a post-synthetic modification approach or using a recognition moiety-appended ligand for preparing MOFs; (ii) construction of small-molecule fluorescent probe@MOF hybrid nanocomposites, in which the MOFs act as a carrier to confine the responsive probe; (iii) based on the target-induced collapse of the MOF structure, etc. Further, the MOF scaffolds exploited for constructing luminescent chemodosimeters are normally required to possess several features, including high stability and dispersibility in aqueous (or aqueous-containing) media, feasibility of installing the recognition moiety for certain analytes, environmental friendliness, and/or good biocompatibility for biosensing and bioimaging applications. Until now, although, dozens of MOF-based chemodosimeters have been reported for different analytes with several desirable traits, such as high selectivity and sensitivity, good stability, and rapid response, some critical performance limitations for this type of luminescent probe still need to be improved, including short-wavelength light excitation and/or emission, insufficient designing strategies for the probe, and limited target analytes. To overcome these shortcomings, several future directions for the design of MOF-based chemodosimeters are proposed herein.

(i) Employing New Rationally Designed Ligands

Most of the developed MOF-based chemodosimeters are ligand-based emission systems. Currently, the used ligand normally belongs to a blue-emissive fluorophore (e.g., BDC) with ultraviolet to blue light excitation, which is unfavorable for applications in complex samples, as well as in bioimaging. Future efforts should focus on the design and utilization of new ligands for constructing luminescent MOFs that have typical spectral features, such as visible/near-infrared emission, two-photon excitation, and large Stokes shifts.

(ii) Developing Dual-Ligand Mofs Systems

Compared with the single-ligand system, the dual-ligand MOFs have greater structural and functional diversity. For example, a fluorescence resonance energy transfer (FRET) sensing system could be achieved by carefully designing the electronic structure of two different ligands. Ratiometric fluorescent probes could be obtained by using one ligand as the target-responsive unit and the other ligand as the internal signal reference.

(iii) Expanding the Application Scope for Mof-Based Chemodosimeters

To date, MOF-based chemodosimeters have only been employed for sensing some ions and small molecules, such as F⁻, Hg²⁺, CN⁻, H₂S, HClO, Cys, H₂O₂, AA, and HT. It is anticipated that future efforts will focus on developing MOF-based chemodosimeters for monitoring other important biomolecules, such as bioenzymes, as well as for bioimaging applications.

In summary, MOF-based luminescent chemodosimeters have increasingly attracted research interest. It can be expected that ongoing studies in this area will lead to the rapid development of more effective luminescent nanomaterials for sensing and imaging applications.