A Luminescent 3d-4f-4d MOF Nanoprobe as a Diagnosis Platform for

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A Luminescent 3d-4f-4d MOF Nanoprobe as a Diagnosis Platform for Human Occupational Exposure to Vinyl Chloride Carcinogen Ji-Na Hao, Xiao-Yu Xu, Xiao Lian, Chi Zhang, and Bing Yan* China-Australia Joint Laboratory of Functional Molecules and Ordered Matters, School of Chemical Science and Engineering, Tongji University, Siping Road 1239, Shanghai 200092, China S Supporting Information *

ABSTRACT: A luminescent nanoprobe based on a lanthanide-transition heterometallic metal−organic framework (MOF) is first designed for specific detection of urinary thiodiglycolic acid (TDGA) which is the biomarker of carcinogenic vinyl chloride monomer (VCM) and represents the internal dose of human exposure to VCM. The nanoprobe demonstrates high selectivity to TDGA with about 27.5-fold luminescence enhancement. It also displays excellent sensitivity with a detection limit as low as 89 ng·mL−1 and fast response to TDGA within 4 min, while refraining from the interference of other coexisting species in urine. Such good sensing performance enables the nanoprobe to practically monitor TDGA levels in human urine. Moreover, a portable urine dipstick based on the sensor is developed to conveniently evaluate individuals’ intoxication degree of VCM. This fast, sensitive, and selective nanoprobe has promising potential to be a useful tool for point-of-care diagnosis of disease associated with VCM exposure.

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INTRODUCTION Vinyl chloride or vinyl chloride monomer (VCM) is a colorless gas at room temperature, and it is an important industrial chemical chiefly used to produce the polymer polyvinyl chloride (PVC).1 VCM is among the top 20 largest petrochemicals in world production, and its estimated annual production was around 2.76 million tons.2 The United States currently remains the largest VCM manufacturing region, and China is also a large manufacturer and one of the largest consumers of VCM. This widely used gas with a sweet odor, however, is highly toxic, flammable, and carcinogenic. VCM was ranked the fourth most threatening chemical compound to human health in 2015 by the Agency for Toxic Substances and Disease Registry (ATSDR).3 Human exposure to VCM can result in cardiovascular (heart and blood), hepatic (liver), and immunological damage.4 Since 1987, VCM has been classified as a group 1 human carcinogen by the International Agency for Research on Cancer (IARC), and exposure to it has been associated with angiosarcoma of the liver (ASL) and hepatocellular carcinoma (HCC).2,5−7 To protect people from developing disease associated with VCM exposure, the environmental VCM level to which they are exposed is periodically monitored to ensure that the air concentrations are below permissible levels. Environmental monitoring, however, cannot reflect people’s actual VCM intoxication because of the heterogeneous factors of individuals. To make a better assessment of individual VCM exposure, biological monitoring, which allows accurate quantification of the pollutant actually absorbed by humans, instead of recording the external exposure levels estimated by environmental monitoring, is a useful way. © 2017 American Chemical Society

Thiodiglycolic acid (TDGA), the main metabolite of VCM in human urine, is taken as a sensitive biomarker in biological monitoring of VCM exposure, since there is a strong proportional correlation between the content of TDGA excreted in urine and the personal VCM exposure level.2,8−11 Therefore, measurement of the urinary TDGA, as markers of internal dose, is an important way of assessing VCM exposure. To date, some methods such as gas chromatography (GC),12 GC-mass spectrography (GC-MS),10,13 isotachophoresis,9,14 voltammetry,15 capillary electrophoresis,16 and liquid chromatography-MS (LC-MS)17 have been well developed to detect TDGA. Nevertheless, these methods still face some challenges like laborious sample processing, usage of toxic reagents, high cost to use, time-consuming operation, or low selectivity and sensitivity. As such, we sought to develop a new TDGAdetecting method that can surmount these challenges of the current methods. Fluorometric detection using fluorescent materials is of great promise due to its simple operability, high selectivity and sensitivity, rapid response, and so on. Luminescent lanthanide metal−organic frameworks (LnMOFs) are very promising and ideal sensing materials for molecular-ion detection owing to not only regular and tunable structures of MOFs but also excellent optical properties of Ln3+.18−21 These Ln-MOFs display recognition abilities for cations,22−26 anions,27−32 and small molecules.20,33−43 However, to the best of our knowledge, luminescent MOF-based sensors for detection of TDGA have never been reported so far. Received: June 19, 2017 Published: September 1, 2017 11176

DOI: 10.1021/acs.inorgchem.7b01549 Inorg. Chem. 2017, 56, 11176−11183

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Figure 1. (a) Schematic illustration showing the design principle of Cu2+/Eu3+-1 as a luminescence probe for TDGA which is the metabolite and biomarker of human exposure to VCM. (b) PXRD patterns of simulated 1, as-synthesized 1 and 1a−1d samples, and TEM images of 1 and 1d samples. °C under vacuum to obtain the final product with a yield of 55% based on the overall weight of ligand and metal salt. Synthesis of 1a. A solution of chloride salts of Eu3+ (0.001 M) in ethanol (10 mL) was added into a 50 mL flask containing 100 mg of freshly prepared compound 1, and the mixture was stirred at room temperature (25 °C) for 20 h. After the reaction, the resultant sample was collected by centrifugation, cleaned with ethanol several times to remove the excessive and physical absorbed Eu cations, and dried at 80 °C under vacuum. Synthesis of 1b−1d. To synthesize the title compound, the asprepared 1a (3 mg) was dispersed in 3 mL of CuCl2·2H2O aqueous solution with different concentrations (0.0001, 0.001, and 0.01 M), respectively, and stirred at room temperature (25 °C) for 1 h. Then, the products were separated by centrifugation, washed 3 times with water, and dried at 80 °C under vacuum. For convenience, the asobtained samples with different Cu2+ doping (0.0001, 0.001, and 0.01 M) are named as 1b, 1c, and 1d. Procedures for TDGA Sensing. The sensing of 1a−1d to TDGA was performed by immersing 1 mg of samples into 3 mL of water and TDGA aqueous solutions (1 mg/mL), respectively. The suspensions were then sonicated and stirred at room temperature for 10 min, and finally, the luminescent spectra of the suspensions were recorded. To test the selectivity of the 1d probe, various aqueous solutions of different urine components, mainly including urea, creatine, creatinine (Cre), uric acid (UA), NaCl, NH4Cl, KCl, Na2SO4, and glucose, were prepared at a concentration of 1 mg/mL. The solutions above (3 mL) were added to tubes containing 1 mg of 1d powders individually, and changes in fluorescence were monitored after a 10 min agitation at room temperature. Test 1d samples for sensitivity, experiments were prepared by adding different concentrations of TDGA aqueous solutions with a similar procedure, and fluorescent spectra of the suspensions were recorded. Procedures for Preparing Urine Test Paper Based on the 1d Sensor. The filter paper was cut into strips of 1 cm × 2.5 cm. The dispersion of 1d (1 mg/mL) in ethanol was dropped on the strips and then left to dry at room temperature. To determine urinary TDGA, the strips with 1d were immersed into urine samples spiked with different concentrations of TDGA for 4 min and then exposed to air for drying.

Herein, to probe TDGA with high selectivity and sensitivity, we design a luminescent nanoprobe based on a Cu2+-Eu3+-Zr4+ heterometallic MOF (Figure 1a). The implantation of Cu2+ can not only tune the luminescence of Eu3+ via the ligand-to-metal energy transfer (LMET) process but also serve as the reactive sites for TDGA.44−46 The strong affinity between TDGA and Cu2+ can change the sensor’s luminescence behaviors by weakening the influence of Cu2+ on the LMET process. Therefore, a fast, sensitive, and selective TDGA sensor is constructed, and it exhibits drastically enhanced luminescence toward TDGA. Its capability to monitor urinary TDGA was further demonstrated.

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EXPERIMENTAL SECTION

Materials and Characterizations. All chemicals (analytical grade) were of commercial origin without purification except that europium chloride was obtained from europium oxides in HCl (37.5%). Powder X-ray diffraction patterns (PXRD) were recorded on a Bruker D8 diffractometer using Cu Kα (λ = 1.5418 Å) radiation, with a step size of 0.02° in 2θ over a range of 5−45°. Fourier transform infrared (FTIR) spectra were collected on a Nexus 912 AO446 infrared spectrum radiometer in the wavenumber range of 4000−400 cm−1 using the KBr pellets. The size and morphology of the materials were observed with a JEOL JEM-2100 F transmission electron microscope (TEM, operating voltage of 200 kV). Nitrogen sorption isotherms at 77 K were measured by a Tristar 3020 analyzer. Eu3+ and Cu2+ quantitative analysis in the materials was performed on an X7 Series inductively coupled plasma mass spectrometer (ICP-MS) (Thermo Elemental, Cheshire, UK) after the samples were decomposed with concentrated nitric acid. The X-ray photoelectron spectroscopy (XPS) spectra were recorded on a RBD upgraded PHI5000C ESCA system (PerkinElmer) with Mg Kα radiation (hυ = 1253.6 eV). The photoluminescence spectra were examined by an Edinburgh FLS 920 fluorescence spectrometer equipped with xenon (450 W) lamps. The outer absolute luminescent quantum efficiency was determined by an integrating sphere (150 mm diameter, BaSO4 coating) from Edinburgh FLS 920 instrument. Synthesis of 1. In a typical synthesis procedure of compound 1, ZrCl4 (0.2330 g), 1,2,4,5-benzenetetracarboxylic acid (H4btec, 0.4321 g), and distilled water (5 mL) were mixed in a 50 mL flask under stirring at room temperature, and then the reaction mixture was heated under reflux for 24 h to yield a white gel.47 The resulting product was separated by centrifugation and washed several times with distilled water. The solid was then dispersed in distilled water (∼10 mL per 1 g of product) and heated under reflux for 16 h. This process was carried out to wash out the organic species encapsulated in the pores. After removal of the residual organic species within the pores, the sample was collected by centrifugation, washed with ethanol, and dried at 80

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RESULTS AND DISCUSSION Characterizations of Nanocomposites. The pristine framework Zr6O 4(OH)4(O2C-C6H2 -CO2 (CO 2H)2 )6·xH2O (known as Uio-66(Zr)-(COOH)2, 1) is synthesized by heating the mixture of ZrCl4 and H4btec ligand in water under reflux for 24 h.47 As for the as-prepared 1, the XRD positions of the experimental and simulated patterns coincide with each other (Figure 1b), demonstrating the successful synthesis of 1 with pure phase. Transmission electron microscopy (TEM) studies 11177

DOI: 10.1021/acs.inorgchem.7b01549 Inorg. Chem. 2017, 56, 11176−11183

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for 1b−1d, respectively). This result is roughly consistent with the ICP-MS data (Table S1). Luminescence Properties. The luminescence spectra of the various modified materials (1a−1d) in the suspension state were examined at room temperature and recorded in Figures S5 and S6. The excitation spectrum of 1a monitored at the maximum emission (614 nm) of Eu3+ exhibits a broad band with a maximum absorption at ∼310 nm, which originates from the absorption of the H4btec ligands. However, upon excitation at 310 nm, there is almost no apparent ligand-centered broad emission (360−550 nm) in the luminescence spectrum of the single Eu3+-doped 1 (1a); instead, the Eu3+ ions’ characteristic sharp emissions at 579, 592, 614, 652, and 697 nm, arising from the 5D0 → 7FJ (J = 1, 2, 3, 4) transitions of Eu3+, are obviously observed. This indicates the occurrence of efficient energy transfer from the sensitizer (H4btec) to the doped Eu3+ in 1a. The luminescence quantum yield (η) of 1a was measured to be as high as 29.28%, which further supports the efficient energy transfer process. Under UV irradiation, 1a displays a bright red color luminescence, which is readily observed with the naked eye, qualitatively indicating the sensitization of Eu3+ by 1. By contrast, in Eu3+/Cu2+-codoped 1 (1b−1d), the gradual increase of the Cu2+-doping amount induces the dramatic decrease of the emission of Eu3+ and meanwhile the remarkably obvious of the ligand-based emission, as shown in Figure S6. This suggests that the implantation of Cu2+ lowers the energy transfer efficiency from ligand to Eu3+ since Cu2+ has an unsaturated electron configuration (3d9) and low-lying metalcentered levels formed by their partially filled d-orbital. The d− d transitions among these levels are nonemissive, which lead to strong reabsorption and thus weaken the Eu3+’s luminescence.52 The greatly reduced η value (2.42%) of 1d also indicates the energy transfer efficiency is significantly reduced by Cu2+. As a result, the luminesce color of 1d under the UV lamp changes to dark. Inspired by the fact that the Ln3+’s luminescence depends on the ligand-to-Ln energy transfer efficiency which can be tuned by some guest molecules via guest−metal and guest−ligand interactions, we employed the fabricated nanocomposites as fluorescent sensors for hazardous substances. Sensing Performance for TDGA. VCM exposure can result in angiosarcoma and hepatocellular cancer and has been classified as a group 1 carcinogen by IARC.2,5 The establishment of rapid and accurate detecting technologies for VCM, therefore, is of great importance for environmental pollution prevention and human health protection. TDGA, a detectable metabolite of VCM in human urine, is considered as a sensitive biomarker of VCM and reflects the internal dose of human exposure to VCM.2,6 The measurement of urinary TDGA will be a useful way of monitoring VCM exposure, and thus the nanocomposite we designed is used as a luminescent sensor to detect TDGA. To be qualified as a luminescent sensor for TDGA which is distributed in the aqueous phase, water toleration is essential to the materials. Therefore, the stability of a representative sample (1d) in water was examined. The PXRD in Figure S7a reveals that the framework of 1d is still retained well after storage in water for 2 days. The photoluminescence intensity of 1d maintains >95% of its initial value when measured over a period of 2 days (Figure S7b). It is illustrated that 1d possesses structural stability and photostability. In addition, the acid−base stability of 1d was also investigated since the urine pH value ranges from 4.6 to 8.0. As shown in Figure S8, 1d shows steady fluorescence and a

(Figure 1b) demonstrate that the phase-pure product consists of homogeneous nanoparticles with particle sizes ranging from 30 to 50 nm. The framework of 1 is composed of a Zr6octahedra Zr6O4(OH)4 secondary building unit, which is bridged by the carboxyl groups in 1,2-positions of the H4btec ligand to form a three-dimensional framework with tetrahedral and octahedral cages (Figure 1a). The two remaining carboxyl functions in 2,5-positions of the ligand are noncoordinated, as proved by the characteristic vibrating peak of free carboxyl at 1715 cm−1 in IR spectra (Figure S1a), which provides a platform for the chelation of metal cations. The Brunauer− Emmett−Teller (BET) surface area of the as-obtained 1 is determined to be 400 m2·g−1 (Figure S1b), indicating that the activated 1 is sufficiently porous to allow access of the metal cations to the interior of the lattice. The perfect combination of the accessible sites and the permanent porosity of 1 encourages us to employ it as a host to encapsulate Eu3+ and Cu2+ for the preparation of tunable fluorescent materials. Therefore, the Eu3+-1 (1a, without Cu2+) and Eu3+/Cu2+-1 (1b−1d, 1d with maximum Cu2+) nanocomposites were obtained by reacting 1 with chloride salts of Eu3+ and Cu2+ in ethanol. X-ray photoelectron spectroscopy (XPS) characterization of 1 and 1d was employed to verify the coordination interaction between the free carboxyl moieties on the MOF and the loaded metal ions. The full survey of 1d (Figure S2) displays peaks at 134.2 and 932.6 eV for Eu 4d and Cu 2p, respectively, confirming the existence of Eu3+ and Cu2+ in the materials. The O 1s, Eu 4d, and Cu 2p XPS spectra are enlarged in Figure S2. It is found that the O 1s peak at 529.3 eV in 1 shifts to 530.6 eV upon incorporation of Eu3+ and Cu2+, and the 1d’s Eu 4d and Cu 2p peak positions are both lower than those of the EuCl3 (135.2 eV) and CuCl2 (934.2 eV). These results can be attributed to the formation of M-O coordination bands between metal cations and free carboxyl on 1’s ligands, causing the chelate metal cations’ electron density increase and their binding energy decrease, conversely, resulting in a decrease in the electron density of O and an increase in its the binding energy.40,48,49 The almost disappeared IR absorption (∼1715 cm−1) of the uncoordinated −COOH groups in 1 after chelating metal cations also evidences the coordination interaction between free carboxyl and the loaded metal cations (Figure S1a). The successful modified samples were also characterized by PXRD and TEM (Figure 1b), which indicate that the crystalline integrity and the morphology of 1 are not affected upon metal coordination. Being consistent with the successful loading of Eu3+ and Cu2+, the N2 sorption measurement of 1d (Figure S1b) results in a reduced BET surface area of 282 m2 g−1 owing to the steric hindrance effect of the metal cations within the pores of 1.50,51 The EDX mapping images of 1d provide additional evidence of the existence and distribution of Eu and Cu elements (Figure S3), in which the uniform distribution of Zr, Cu, and Eu elements in the material can be clearly seen. The metal cations’ loading level in 1a−1d was quantified by ICP-MS measurement (Table S1), which shows the molar ratio of Zr:Eu in 1a−1d is around 21 and the molar ratios of Zr:Cu in 1b−1d are 228, 42, and 8.8, respectively. The thermogravimetric analysis of 1−1d samples were further performed. Figure S4 exhibits that the framework is thermally stable up to 350 °C. Above this temperature, the weight loss observed can be attributed to the degradation of the framework, leading to the formation of ZrO2 (20.17 wt %), Eu2O3 (1.425 wt %), and CuO (0.057, 0.306, and 1.487 wt % 11178

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Figure 2. Suspension-state luminescence spectra of 1a−1d before (black line) and after (red line) adding TDGA (λex = 310 nm). Inset: the changes in the emission intensities of Eu3+ (614 nm) after treated with TDGA.

Figure 3. (a) The emission spectra of the 1d upon treatment with TDGA at various time intervals (λex = 310 nm). (b) The luminescence intensity of 1d at 614 nm as a function of immersion time in TDGA aqueous solution.

Figure 4. (a) Suspension-state luminescence spectra and (b) intensities (the 5D0 → 7F2 transition, 614 nm) of 1d toward various urine components (λex = 310 nm). Inset in (b): the corresponding photographs under a UV lamp (254 nm).

of Eu3+ almost remains unchanged before and after adding TDGA. The results indicate that the Cu2+ ions incorporated into the samples play a significant and crucial role in realizing the recognition of TDGA and a higher Cu2+ loading favors the probe’s response for TDGA. The 1d sensor whose Cu2+ content is the highest shows the most efficient response (27.6-fold increase) toward TDGA, and its luminescence color after being treated by TDGA changes from colorless to red when observed with the naked eye under a UV lamp (inset in Figure 2). Of particular note is that the TDGA-induced luminescence enhancement reaction is very fast, as demonstrated by the time-dependent emission spectra and intensity curve in Figure 3. The luminescence intensity of 1d at 614 nm shows a sharp increase (∼24.9-fold) after addition of TDGA for 1 min and levels off in 4 min. To obtain a deeper insight into the sensing performance of the TDGA sensor, attention is focused on the 1d probe, which is the most efficient for TDGA detection.

stable structure in the urine pH range, indicating the good pHindependent stability of 1d. These results indicate that the nanocomposites are competent for sensing application in urine environment. The design principle of probing TDGA was to introduce the reactive site (Cu2+) for TDGA into the framework as the TDGA-responding site. Cu2+ has been found to be able to quench the Eu3+’s luminescence. TDGA has a strong affinity for Cu2+, which as a result weakens the quenching effect of Cu2+ on the emission of Eu3+ (Figure 1a). Thereby, in the presence of TDGA, the enhanced luminescence of Cu2+/Eu3+-1 (1b−1d) would be observed. To demonstrate the feasibility of our design strategy, the luminescence behaviors of 1b−1d toward TDGA were investigated. As shown in Figure 2, the addition of TDGA (1 mg·mL−1) into the 1b−1d suspensions triggers an apparent enhancement of the Eu3+ ions’ emission in the materials, as expected. Their luminescence intensities of Eu3+ at 614 nm show a 1.54-, 11.84-, and 27.56-fold increase, respectively. In the 1a sample, without Cu2+ doping, the luminescence intensity 11179

DOI: 10.1021/acs.inorgchem.7b01549 Inorg. Chem. 2017, 56, 11176−11183

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enhancement response is unaffected in the background of other coexisting urine ingredients, demonstrating the good antiinterference performance and high selectivity of 1d for TDGA. The high selectivity can be attributed to the strong and specific affinity between 1d and TDGA. Sensitivity is a key factor in assessing the performance of a probe. To evaluate the sensitivity of 1d toward TDGA, the fluorescence responses of 1d with different concentrations of TDGA were further investigated. As shown in Figure 6a,b, the emission signals of Eu3+ in 1d are found to gradually increase with the increasing addition amount of TDGA and tend to saturate when the concentration exceeds 700 mg/L. The luminescence intensities of Eu3+ at 614 nm in 1d exhibit excellent linear dependence on the concentration of TDGA in a large concentration range spanning about 3 orders of magnitude (0−700 mg/L). This linear relationship between the emission intensity (IEu) and [TDGA] can be fitted as a function of eq 1

To determine whether 1d can act as a highly selective chemosensor for TDGA, a selectivity test of 1d toward other typical urine components such as creatine, creatinine (Cre), urea, uric acid (UA), Na+, K+, NH4+, Cl−, SO42−, and glucose (Glu) was conducted under the same conditions. In contrast to TDGA, the additions of these components only cause negligible changes in the luminescence spectra (Figure 4). In accordance with the spectral changes, under a UV lamp irradiation, only TDGA induces a visible color change from colorless to red. The differences in the effects on 1d emission between TDGA and other urine components can be easily distinguished by the naked eye, indicating 1d can act as a visually selective sensor for specific recognition of TDGA. A critical characteristic for a selective sensor is its ability to distinguish the target analyte under the interference of other coexisting species. Therefore, the interference experiments were carried out to investigate the anti-jamming capability of the 1d sensor. Figure 5 reveals that the TDGA-induced fluorescence

IEu = 1.088 + 0.0224C TDGA

(1)

with a correlation coefficient (R2) of 0.9878, suggesting that 1d is also potentially useful for the quantitative determination of TDGA. The limit of detection (LOD), defined as 3σ/k (σ is the standard deviation for 20 replicating fluorescence measurements of blank solutions, and k is the slope of the calibration curve),53 was determined to be 89 ng·mL−1 for TDGA. This LOD is more than 200 times lower than the threshold value of 20 mg·L−1 for a healthy person.54 Such a low LOD coupled with the wide linear detection range of TDGA for 1d is highly desirable to fulfill the critical requirement of tracing the urinary TDGA levels for early diagnosis of VCM poisoning. It is worth noting that the 1d sample undergoes a naked-eye color change after being treated by different concentrations of TDGA. As shown in Figure 6c, the colors of the 1d powders change from

Figure 5. Luminescence responses of 1d toward TDGA in the presence of background of other various urine components (λex = 310 nm).

Figure 6. (a) Effects of TDGA concentration on the PL emission of 1d. (b) Plot of luminescence intensity of 1d at 614 nm vs TDGA concentration over the linear range 0−700 mg·L−1. (c) Photographs showing the color changes of the 1d sample after treated by different concentrations of TDGA. (d) Optical images of test paper under 254 nm UV light irradiation after immersing into urine spiked with different concentrations of TDGA (mg/ L). 11180

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findings demonstrate the great potential of such an excellent nanoprobe in practical monitoring of human exposure to VCM, which may pave the way for point-of-care disease diagnosis associated with VCM exposure.

brilliant blue to light blue, and finally almost colorless with the increasing concentration of TDGA from 0 to 700 mg/L; i.e., TDGA’s addition bleaches the blue color of the powders out. ICP-MS measurement was further conducted to determine the content of Cu2+ in TDGA-treated 1d. The results in Table S2 illustrate that the Cu2+ cations are gradually leached out from 1d after treatment with TDGA and thus results in the faded color of the 1d sample. Either the framework collapse of 1d or the strong affinity between Cu2+ and TDGA can be responsible for the leakage of Cu2+. In order to clarify this, the PXRD of 1d after being treated by TDGA was measured (Figure S9), which demonstrates that the framework maintains its integrity after contact with TDGA, thus ruling out the factor of framework collapse. This finding, together with the ICP-MS result, suggests that the strong complexation ability of TDGA for Cu2+ causes the leakage of Cu2+ from 1d and weakens the quenching effect of Cu2+ on Eu3+’s emission, thus leading to the luminescence enhancement with the faded sample color. Application of TDGA Nanoprobe in Urine Samples. To evaluate the applicability of our nanoprobe in practical analysis, the urine specimens spiked with 10, 50, and 300 mg/L of TDGA are analyzed by the 1d probe. The experimental results are listed in Table S3. The urinary TDGA levels measured by this sensor are in good agreement with the actual TDGA amount. The recoveries are in the range of 91.67−103.44%, and the resulting relative standard deviations (RSDs) of all assays are below 4.5%, both of which are within the acceptance criteria and satisfying, thereby verifying the high reliability and practicability of the nanoprobe for TDGA’s detection in real samples. What’s more, it is worthy of emphasizing that a urine dipstick was developed for easy and convenient detection of urinary TDGA. The test stripe was prepared by dropping the ethanol dispersion of 1d on a filter paper (1 × 2.5 cm2) and drying it at room temperature. For the detection of urinary TDGA, the dipsticks are immersed in a series of urine samples spiked with different concentrations of TDGA for 4 min and exposed to air for drying. Then, the optical images of these dried dipsticks under the irradiation of a UV lamp were recorded. As shown in Figure 6d, the luminescent colors of the test stripes change from dark to dark red, faint red, purplish red, and finally bright red as soaked in urine samples with increasing TDGA contents. To the naked eye, one can distinguish the colors of different intensities, thus easily evaluating the intoxication degree of human exposure to VCM.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.7b01549. Structure representation, EDX spectroscopy, thermal gravimetric analysis (TGA) curves, EDX-mapping images, ICP-MS results, PXRD patterns, luminescence spectra, and picture of sensing experiment (PDF)

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AUTHOR INFORMATION

Corresponding Author

*Phone: +86-21-65984663. E-mail: [email protected]. ORCID

Bing Yan: 0000-0002-0216-9454 Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. These authors contributed equally. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is supported by the National Natural Science Foundation of China (21571142), Developing Science Funds of Tongji University and Science & Technology Commission of Shanghai Municipality (14DZ2261100).

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REFERENCES

(1) Dreher, E. L.; Beutel, K. K.; Myers, J. D.; Lübbe, T.; Krieger, S.; Pottenger, L. H. In Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-VCH: Weinheim, 2014; pp 1−81. (2) Huang, P. C.; Liu, L. H.; Shie, R. H.; Tsai, C. H.; Liang, W. Y.; Wang, C. W.; Tsai, C. H.; Chiang, H. C.; Chan, C. C. Assessment of Urinary Thiodiglycolic Acid Exposure in School-Aged Children in the Vicinity of a Petrochemical Complex in Central Taiwan. Environ. Res. 2016, 150, 566−572. (3) Agency for Toxic Substances and Disease Registry (ATSDR). https://www.atsdr.cdc.gov/spl/index.html (accessed Dec 10, 2016). (4) Agency for Toxic Substances and Disease Registry (ATSDR). https://www.atsdr.cdc.gov/toxprofiles/tp20.pdf (accessed Dec 10, 2016). (5) Kumar, A. K.; Balachandar, V.; Arun, M.; Ahanmed, S. A. K. M.; Kumar, S. S.; Balamuralikrishnan, B.; Sankar, K.; Sasikala, K. A Comprehensive Analysis of Plausible Genotoxic Covariates among Workers of a Polyvinyl Chloride Plant Exposed to Vinyl Chloride Monomer. Arch. Environ. Contam. Toxicol. 2013, 64, 652−658. (6) Ward, E.; Boffetta, P.; Andersen, A.; Colin, D.; Comba, P.; Deddens, J. A.; De Santis, M.; Engholm, G.; Hagmar, L.; Langard, S.; Lundberg, I.; McElvenny, D.; Pirastu, R.; Sali, D.; Simonato, L. Update of the Follow-up of Mortality and Cancer Incidence among European Workers Employed in the Vinyl Chloride Industry. Epidemiology 2001, 12, 710−718. (7) Wong, R.-H.; Chen, P.-C.; Du, C.-L.; Wang, J.-D.; Cheng, T.-J. An Increased Standardized Mortality Ratio for Liver Cancer among Polyvinyl Chloride Workers in Taiwan. Occup. Environ. Med. 2002, 59, 405−409.

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CONCLUSIONS In summary, we have successfully designed a luminescent Cu(II)-Eu(III)-Zr(IV) heterometallic MOF-based nanoprobe for detecting TDGA which is the urinary metabolite and biomarker of human exposure to VCM carcinogen. The recognition of TDGA by the sensor is achieved through introducing the reactive site for TDGA into the framework as the TDGA-responding site (Cu2+). As the first example of a luminescent sensor for TDGA, it exhibits a 27.6-fold luminescence enhancement response to TDGA within 4 min without the interference of other coexisting species in urine. It shows a wide linear detection range (0−700 mg/L) and a low detection limit (89 ng/mL), thus allowing for quantitative monitoring of TDGA levels with high sensitivity. Importantly, this fast, selective, and sensitive luminescent nanoprobe enables detection of TDGA in real human urine, and a portable urine test paper based on the sensor was developed to conveniently evaluate individuals’ intoxication degree of VCM. These 11181

DOI: 10.1021/acs.inorgchem.7b01549 Inorg. Chem. 2017, 56, 11176−11183

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DOI: 10.1021/acs.inorgchem.7b01549 Inorg. Chem. 2017, 56, 11176−11183