Phosphonate MOFs Composite as Off–On Fluorescent Sensor for

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Phosphonate MOFs Composite as Off−On Fluorescent Sensor for Detecting Purine Metabolite Uric Acid and Diagnosing Hyperuricuria Xiao Lian and Bing Yan* Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Siping Road 1239, Shanghai 200092, P. R. China S Supporting Information *

ABSTRACT: The recent discovery of lanthanide organic frameworks (Ln-MOFs) offers the potential for biomarkers or metabolites sensing. This is another field that is closely connected with life science and medicine. In this work, a stable and luminescent phosphonate Ln-MOFs MIL-91(Al:Eu) and its derivatives composite Cu2+@MIL-91(Al:Eu) were synthesized. The rebound of luminescence of Cu2+@MIL-91(Al:Eu) that origin of Eu3+ is observed in the presence of uric acid. This On−Off−On pattern is utilized for detecting uric acid, which is the final metabolite of purine. The composite reveals excellent selectivity and sensitivity for sensing uric acid. The detection of uric acid in real urine is also investigated. The effective detection of uric acid and tentative diagnosis of hyperuricuria on the basis of test paper is demonstrated.

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INTRODUCTION Uric acid (2,6,8-trihydroxypurine, UA) is the final product of purine metabolism in vivo. 1−3 The fast and reliable determination of uric acid for diagnosing hyperuricuria is very important, because the abnormal content of uric acid in urine could increase the risk of disease, such as leucocythemia, heavy hepatitis, gout, cardiovascular, and kidney diseases.4,5 A variety of methods for the detection of uric acid in human serum has been reported, such as optical methods,6−10 electroanalysis,11,12 and high-performance liquid chromatography.13 Among most of the mentioned methods, fluorescence sensors possesses a series of advantages, such as low cost, convenience, and repeatability. However, most of the testing methods are to detect uric acid in serum. But 60−70% of uric acid is excreted through the kidneys, and it eventually appears in the urine discharged from the human body.14 Therefore, it is necessary to develop new methods for detecting uric acid in urine and for observational measured hyperuricuria. Lanthanide metal−organic frameworks (Ln-MOFs) are a kind of material with excellent optical properties that consists of measureless networks of lanthanide ions centers connected to organic ligands by coordinate bonds.15−17 Among the multitudinous researches of functional MOFs, luminescence of LnMOFs has attracted great attention for their prominent fluorescence properties that originated from the abundant 4f−4f transitions of trivalent lanthanide ions.18,19 Ln-MOFs offer the possibility of exploiting the luminescence performance of lanthanide cations such as extended emission lifetimes with sharp and characteristic line emissions. In addition, the luminescent intensity of Ln-MOFs could be tuned by the © 2017 American Chemical Society

host−guest interaction, thereby providing an opportunity for chemical sensing of various chemical species such as cations,20−22 anions,23,24 organic molecules,25−28 and biomarkers or metabolites.29,30 Biomarkers or metabolites sensing based on the Ln-MOFs is an emerging but burgeoning method in biochemistry and medical science. Herein, we synthesize a phosphonate MOFs MIL-91(Al:Eu) and modified it to a composite to detect uric acid. Compared with the conventional carboxylate MOFs, MIL-91 is constituted of a piperazine derivative ligand N,N′-piperazinebismethylphosphonic acid instead of carboxylic ligand. Phosphonate MOFs are much more stable and more difficult to destroy in various environments than carboxylate MOFs.31,32 That means the MIL-91 can withstand a variety of chemical environments for further practical applications. The nonblooming composite Cu2+@MIL-91(Al:Eu) can be utilized to detect uric acid due to the rebound of luminescence in the presence of uric acid. The limit of detection (LOD) is determined and proved that Cu2+@ MIL-91(Al:Eu) can be used to detect uric acid in urine. In addition, the composite powders and test papers are demonstrated for rapidly detecting abnormal levels of uric acid in urine. It provides a novel method for the convenient and nimble diagnosis of hyperuricuria.

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EXPERIMENTAL SECTION

Materials and Instrumentation. All reagents and solvents in this work are commercially available and at least of analytical grade. Received: December 12, 2016 Published: March 30, 2017 6802

DOI: 10.1021/acs.inorgchem.6b03009 Inorg. Chem. 2017, 56, 6802−6808

Article

Inorganic Chemistry

Figure 1. (a)The PXRD pattern of simulated result, MIL-91(Al:Eu) and Cu2+@MIL-91(Al:Eu); (b) N2 adsorption−desorption isotherms of MIL91(Al:Eu) and Cu2+@MIL-91(Al:Eu); (c) SEM image of MIL-91(Al:Eu); (d) SEM image of Cu2+@MIL-91(Al:Eu). Europium nitrate Eu(NO3)3·6H2O was prepared by dissolving the europium oxide in concentrated nitric acid with heating and stirring to promote the reaction. All chemicals were used without further purification. X-ray powder diffraction (PXRD) patterns were recorded with a Bruker D8 Advance diffractometer using Cu Kα radiation with 40 mA and 40 Kv. Fourier transform infrared (FTIR) spectra were measured within KBr slices from 4000 to 400 cm−1 using a Nicolet IS10 infrared spectrum radiometer. Thermogravimetric (TG) analysis was measured using a Netzsch STA 449C system at a heating rate of 15 K min−1 under nitrogen protection. Scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDX) were conducted on a Hitachi S-4800 field emission scanning electron microscope operating at 15 kV. Measurement of Eu3+ and Al3+ was performed on an X-7 series inductively coupled plasma-mass spectrometer (ICP-MS; Thermo Elemental, Cheshire, U.K.). Nuclear magnetic resonance (NMR) spectroscopy (400 MHz) was performed on a Bruker Avance III spectrometer. Elemental analysis was performed by a vario EL III Element Analyzer. Visible absorption spectra were made on an Agilent 8453 spectrometer. Photoluminescence spectra and luminescence lifetimes (τ) were examined by an Edinburgh Analytical Instruments FLS920. Outer absolute luminescent quantum efficiency was determined employing an integrating sphere (150 mm diameter, BaSO4 coating) from Edinburgh FLS920 phosphorimeter. Spectra were corrected for variations in the output of the excitation source and for variations in the detector response. The quantum yield could be defined as the integrated intensity of the luminescence signal divided by the integrated intensity of the absorption signal. Synthesize for N,N′-Piperazinebismethylphosphonic Acid. The ligand N,N′-piperazinebismethylphosphonic acid was synthesized using a Mannich reaction with some modification.33 In a typical preparation of a diphosphonic acid, piperazine (0.09 mol, 7.57 g, Adamas, 98%) was dissolved in distilled water (70 mL) with phosphorous acid (0.23 mol, 19.19 g, Adamas, 99%) and hydrobromic acid (74 mL, 45 wt % aqueous solutions, Adamas). Formaldehyde (38.5 mL, 0.52 mol, Adamas, 38 wt % aqueous solutions) was cautiously added to the above mixture over 20 min. The reaction was refluxed at 120 °C for 20 h after which time a white precipitate was observed. When cooled, solvent volume was reduced to ∼50%, and the reaction mixture was kept at 4 °C overnight to ensure precipitation of

the product. The product was separated by centrifugation, washed with an ethanol−water solution (9:1), and dried overnight at 40 °C. The FTIR spectrum of the as-synthesized N,N′-piperazinebismethylphosphonic acid was shown in the Figure S1, Supporting Information. N,N′-Piperazinebismethylphosphonic acid (3 mg) was digested and dissolved with sonication in 0.60 mL of deuterated dimethyl sulfoxide (DMSO-d6) and 0.55 mL of DCl solution (20% DCl in D2O solution). The digestion solution was used directly for 1H NMR measurement. The 1H NMR data of it were as follows: 2.32 (8H, s), 2.75 (4H, d). The corresponding spectra was presented in the Figure S2, Supporting Information. Synthesis for MIL-91(Al:Eu) and Cu2+@MIL-91(Al:Eu). The aluminum analogue of MIL-91 was first prepared by aluminum chloride hydrate (AlCl3·6H2O, Sinopharm Chemical Reagent Co., Ltd., AR) and N,N′-piperazinebismethylphosphonic acid.34,35 In a modified preparation, the aluminum chloride, europium nitrate, and N,N′-piperazinebismethylphosphonic acid were mixed for 1 h at 343 K in water in the molar ratio of 1.33:0.066:1:900. The pH was controlled to 5 through 1 M NaOH solution. The resulting mixture was transferred to a polytetrafluoroethylene (PTFE)-lined autoclave for hydrothermal reaction at 463 K for 130 h, and a white crystalline powder was obtained finally. Elemental analysis gave C 19.35%, H 5.33%, N 7.21% (calculated for Al0.95Eu0.05C6H15N2O7P2·3H2O: C 19.14%, H 5.62%, N 7.44%). The Cu2+@MIL-91(Al:Eu) composite was prepared by MIL91(Al:Eu) and nantokite solution. The as-synthesized MIL-91(Al:Eu) was immersed in 1 M Cu(NO3)2 aqueous solution (formula as Cu(NO3)2·3H2O for solid, Adamas, 99%) for 2 h with sustained stirring. The bluish product was isolated by centrifugation and airdried. Elemental analysis of Cu2+@MIL-91(Al:Eu) gave C 19.27%, H 5.40%, N 7.29% (calculated for [email protected]· 3H2O: C 19.10%, H 5.61%, N 7.42%). Some other composites were also prepared and named M@MIL91(Al:Eu) (M represents different metal cations that were introduced in the primitive MOFs, including K+, Ca2+, Na+, Al3+, Zn2+, Fe2+, Fe3+, Hg2+, Ag+, Cr3+, Cd2+, Ni2+, and Co2+). The luminescent measurement for the solid-state composite was studied subsequently. Luminescent Sensing Experiment. For the experiments of sensing urine chemicals, 3.0 mg of Cu2+@MIL-91(Al:Eu) powders 6803

DOI: 10.1021/acs.inorgchem.6b03009 Inorg. Chem. 2017, 56, 6802−6808

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Inorganic Chemistry

Figure 2. Excitation spectra and emission spectra of N,N′-piperazinebismethylpho-sphonic acid (left) and MIL-91(Al:Eu) (right). were simply immersed into the aqueous solutions (3 mL, 10 mM) of different urine chemicals, include creatinine (Cre), creatine, KCl, NaCl, Na3PO4, NH4Cl, urea, uric acid (UA), glucose (Glu), hippuric acid (HA). Then the luminescence spectra of suspensions were measured after sonicating for 15 min.36 Water Stability Investigation of Cu2+@MIL-91(Al:Eu). The structural stability of Cu2+@MIL-91(Al:Eu) in water was examined by immersing the as-synthesized samples (10 mg) in water (10 mL) for different time at room temperature. After a maximum of 2 d of immersion, the samples were separated and dried before PXRD measurement. Luminescence stability of Cu2+@MIL-91(Al:Eu) was tested by immersing 3 mg of the as-synthesized samples in 3 mL of H2O. After ultrasonic treatment, the luminescence spectra of the suspension were recorded. Afterward, the suspension was sealed in a glass bottle (5 mL) and kept statically for 3 d; then, the sample was sonicated for 5 min, and the suspension state luminescent measurement was recorded. After another 2 d soakage water, the emission spectrum of Cu2+@MIL91(Al:Eu) in water was measured again. pH Stability Investigation of Cu2+@MIL-91(Al:Eu). The structural stability investigation of Cu2+@MIL-91(Al:Eu) in aqueous solutions with the pH value ranging from 4 to 8:10 mg of Cu2+@MIL91(Al:Eu) powders was immersed in each aqueous solution (10 mL) with a pH value of 4, 5, 6, 7, 8, respectively, and then sealed in glass bottles (20 mL). The bottles were kept statically for 72 h, and then the samples were collected via centrifugation and air-dried. Subsequently, PXRD were measured. The pH-independent luminescent stability: 3 mg of Cu2+@MIL91(Al:Eu) was immersed in 3 mL of aqueous solutions with pH value ranging from 4 to 8 for 12 h, and then the suspension-state luminescence spectra were measured after sonicating for 5 min. Experimental Details for Preparing Urine Test Paper Based on the Fluorescent Sensor. The filter paper was cut into strips of 1 cm × 3 cm. The dispersion of Cu2+@MIL-91(Al:Eu) (2 mg/mL) in ethanol was dropped on the strips and then left to dry at room temperature. For determination of HA in urine, the strips with Cu2+@ MIL-91(Al:Eu) were immersed into urine sample for 1 min and then exposed to air for drying.

three oxygen atoms; the remaining one oxygen atom of PO3C group occupies a termination position. PXRD pattern of assynthesized MIL-91(Al:Eu) gives several peaks in 2Θ range of 5−50° (Figure 1a), which is matching well with the simulated pattern. In addition, the structure of the prepared Cu2+@MIL91(Al:Eu) is also confirmed by XRD, suggesting that the identical structure of MIL-91(Al:Eu) is invariable after treatment with the solution of copper ions. Morphology of MOF materials is studied by scanning electron micrograph (SEM). As shown in Figure 1c,d and Figure S4 (Supporting Information), many uniform rodlike crystals formed the sample of MIL-91(Al:Eu), and the morphology of MIL-91(Al:Eu) does not change after copper ion substitution. The composition of MOFs materials is subsequently examined by energy-dispersive X-ray analysis (EDX) spectroscopy and ICP-MS (Figure S5 and Table S1, Supporting Information). According to the ICP-MS results, it can be predicted the molar ratio of Al:Eu for MIL-91(Al:Eu) is close to 19.1:1, which is in accord with the initial feed ratio (molar ratio of Al/Eu = 20.15:1) in the synthetic experiment. The corresponding value of Cu2+@MIL-91(Al:Eu) is Al/Eu/ Cu = 19:1:0.25. The thermal behavior of MIL-91(Al:Eu) displays a weightlessness of 14.8 wt % under 473 K (Figure S6, Supporting Information), which is belonging to the loss of physisorbed water in the frameworks. TGA curve reveals a distinct weightlessness between 490 and 600 K, which is vest in the Al−OH−Al chains of MIL-91(Al) is likely to dehydroxylation and dehydration. The thermal stability of MIL-91(Al) is better than MIL-91(Al:Eu); this may be because the Eu−O bond is more unstable than Al−O chains. N2 adsorption− desorption isotherms of MIL-91(Al:Eu) and Cu2+@MIL91(Al:Eu) are illustrated in Figure 1b. Unlike the type I adsorption curve, the Brunauer−Emmett−Teller (BET) curve of MIL-91(Al:Eu) is more like microporous material; it shows typically a type IV curve with adsorption hysteresis loops at high pressure. The typical hysteresis loops of these isotherms can put it down to the steric hindrance of the free PO groups within the frameworks, which could reduce the entry of N2 molecules. The BET surface area of Cu2+@MIL-91(Al:Eu) is 172 m2 g−1, which shows rational decrease compared with the corresponding value of MIL-91(Al:Eu) (269 m2 g−1) due to the encapsulation of Cu2+. This small surface area is consistent with the previous description of phosphonate MOFs. Photoluminescence Properties of MIL-91(Al:Eu) and Cu2+@MIL-91(Al:Eu). The emission spectrum of the ligand

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RESULTS AND DISCUSSION Physical Characterization of MIL-91(Al:Eu) and Cu2+@ MIL-91(Al:Eu). MIL-91(Al:Eu) is prepared by solvothermal method; the structure of the framework is shown in Figure S3 (Supporting Information) for the aluminum analogue. The structure of MIL-91 is built from the linkage of chains of M(OH)2O4 octahedral geometry by sharing corner and protonated bisphosphonate groups with two kinds of coalescent: M−X−M and M−O−P (M = Al, Eu; X = O, OH). Each PO3C group of the framework serves as a bridging linker to coordinate with metal cations and shares two of its 6804

DOI: 10.1021/acs.inorgchem.6b03009 Inorg. Chem. 2017, 56, 6802−6808

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Inorganic Chemistry

Sensing for Uric Acid in Aqueous Solutions. Guided by the fluorescence quenching effect of MIL-91(Al:Eu) that was caused by Cu2+ and Fe3+, we think that this material can be further designed and used for the detection of uric acid. To examine whether M@MIL-91(Al:Eu) (Mn+ = Cu2+, Fe3+) possesses the potential as a fluorescent probe for uric acid, it is immersed in different aqueous solutions of various species that are common ingredients in urine, including creatinine (Cre), creatine, KCl, NaCl, Na3PO4, NH4Cl, urea, uric acid (UA), glucose (Glu), and hippuric acid (HA). Then the luminescence spectra of suspensions are measured after sonicating for 15 min. The suspension-state luminescence measurements are accounted for and are compared in Figure 3 and Figure 4,

N,N′-piperazinebismethylphosphonic acid reveals a broad peak centered at 380 nm when it is excited by 312 nm light source (Figure 2), which could be attributed to the π−π* electrons transition of organic linkers. The excitation and emission spectra of MIL-91(Al:Eu) are displayed in Figure 3; the

Figure 3. Emission spectra of Cu2+@MIL-91(Al:Eu) after immersion in various urine chemicals solutions.

luminescence of MIL-91(Al:Eu) is attributed to the energy transfer from the excited energy levels of organic ligand to the ground state of lanthanide ions, and then the Eu3+ ions exhibit sharp and strong emission. The emission peaks of MIL91(Al:Eu) located at ∼579, 589, 612, 652, and 702 nm are assigned to 5D0→7FJ (J = 0, 1, 2, 3, 4) transitions, respectively. The 5D0→7F2 transition has maximum luminescent intensity, which is often attributed to the low symmetry of the Eu3+, demonstrating that the incorporated Eu3+ is located at antiinversion symmetry. This is further proved by the presence of 5 D0→7F0 transition; the occurrence of it is a well-known example that the Eu3+ occupies a site with Cnv, Cn, or Cs symmetry. It is worth noting that the broad emission of the ligand N,N′-piperazinebismethylphosphonic acid does not appear in the emission spectrum of MIL-91(Al:Eu), which indicates the antenna effect occurred. The ligand-centered (LC) transition of the N,N′-piperazinebismethylphosphonic acid is restrained by the ligand-to-metal charge transfer (LMCT) from ligand to Eu3+ ions by intersystem crossing transfer. To investigate of the photoluminescence properties of Cu2+@MIL-91(Al:Eu), we measure the photoluminescence (PL) spectra of various MOFs composite M@MIL-91(Al:Eu) (M represents different metal cations introduced in the primitive MOFs, including K+, Ca2+, Na+, Al3+, Zn2+, Fe2+, Fe3+, Cu2+, Hg2+, Ag+, Cr3+, Cd2+, Ni2+, and Co2+), and the composites are stable undergoing various metal ions introduced, confirmed by PXRD (Figure S7, Supporting Information). The luminescence spectra are presented in Figure S8, Supporting Information. It can be seen that the fluorescence intensity of some M@MIL-91(Al:Eu) composites is weakened compared with the MIL-91(Al:Eu). As shown in the histogram on the basis of the intensity of 5D0→7F2 transition of Eu3+ (Figure S9, Supporting Information), Cu2+ and Fe3+ reveal a prominent quenching effect for the luminescence of Eu3+. Cu2+ and Fe3+ are both easy to coordinate with uric acid, which provides a way for us to use the material to detect uric acid.

Figure 4. Histogram based on the intensity of 5D0→7F2 transition of Eu3+ in Cu2+@MIL-91(Al:Eu) toward various urine chemicals.

respectively. The results for Cu2+@MIL-91(Al:Eu) clearly show that only uric acid induced a remarkable rebound in the luminescence intensity of Eu3+ at 612 nm. But there are nearly no changes of the fluorescence intensity of Cu2+@MIL91(Al:Eu) that can be observed with other urine chemicals. Furthermore, the mechanism for this luminescence rebound is further investigated. As shown in the Figure S10 (Supporting Information), the spectra of MIL-91(Al:Eu) with water and uric acid, as well as the spectra of Cu 2+ @MIL-91(Al:Eu) suspensions with or without uric acid, are recorded. Uric acid cannot influence the fluorescence of MIL-91(Al:Eu), so that the MIL-91(Al:Eu) with uric acid displays a similar spectrum with that of MIL-91(Al:Eu) suspensions. But the Cu2+@MIL91(Al:Eu) composite shows almost no fluorescence emission; the quench effect of Cu2+ for 4f−4f emission of Eu3+ is obvious. However, with the addition of uric acid into Cu2+@MIL91(Al:Eu) suspensions, the luminescence intensity is recovered. Consistent with the changes of luminescence intensity, under UV irradiation, the UA-incorporated Cu2+@MIL-91(Al:Eu) shows significantly stronger luminescence than the Cu2+@MIL91(Al:Eu) alone, and it could be clearly distinguished using eyes (Figure S11, Supporting Information). That means the interaction like coordinate bond between uric acid and copper ions is the major factor that leads to the fluorescence recovery. In contrast to the visible absorption spectra of Cu2+ solution and mixed solution of Cu2+ and UA (Figure S12, Supporting Information), the absorption peak shifted from 797 to 689 nm, which is a typical blue shift in absorption spectroscopy. This shift indicated that there is an interaction like coordination bond between Cu2+ and UA. This change can be also observed from the Figure S10 (Supporting Information); the color of Cu2+@MIL-91(Al:Eu) is changed from watchet blue to light 6805

DOI: 10.1021/acs.inorgchem.6b03009 Inorg. Chem. 2017, 56, 6802−6808

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Inorganic Chemistry

Figure 5. PL spectra (a) and luminescence responses (b) of Cu2+@MIL-91(Al:Eu) upon addition of UA in the presence of a background concentration of various urine chemicals (0.01 M) in aqueous solution; the blue column presents the luminescence intensity of composite without uric acid and the red conversely.

Figure 6. (a) The luminescence spectra of Cu2+@MIL-91(Al:Eu) in the presence of different concentrations of uric acid aqueous solution, and the plot of I0/I vs the logarithm of the concentration of uric acid. (b, c) Test papers under light and UV irradiation.

brown. However, in the spectra of Fe3+@MIL-91(Al:Eu), we found fluorescence enhancement neither within uric acid nor other chemicals. We suspect that this difference is caused by the different coordination modes of the metal ions and uric acid and the kinetic factors. In the human body, uric acid is the most likely to coordinate with Fe3+ rather than Cu2+. But in experimental condition, some influencing factors like temperature, pH value, and reaction time maybe hinder the coordination between Fe3+ and uric acid. In addition, structural and luminescent stability of Cu2+@ MIL-91(Al:Eu) under aqueous surroundings also were investigated. The frame of the sensor is water-stable, which is validated by PXRD of the sample immersed in water for 24 h (Figure S13, Supporting Information), which indicates the crystal structure of Cu2+@MIL-91(Al:Eu) remained without any change. The fluorescence intensity of Cu2+@MIL-91(Al:Eu) shows no evident change during storage in water for 24 h (Figure S14 Supporting Information), implying that Cu2+ is immobilized securely in the Cu2+@MIL-91(Al:Eu). Similar experiments are processed under different pH solutions. The PXRD and luminescentce intensity histogram (Figures S15 and S16, Supporting Information) demonstrate that the structure and luminescence intensity of Cu2+@MIL-91(Al:Eu) has no

obvious change in different pH environment (pH = 4.0−8.0). Good stability to be compatible with various environments makes the composite capability for fluorescent sensors in aqueous media. Recyclable performance of sensor materials plays a significant role for practical applications. Therefore, we investigate the recovery experiment of Cu2+@MIL-91(Al:Eu). As shown in Figure S17, after the fluorescence rebound caused by UA, the fluorescence intensity reduced to the level before UA addition after ultrasonic washing. After four recycles performed by successive addition of UA and ultrasonic washing, the luminescence of the recycled Cu2+@MIL-91(Al:Eu) is similar to those of the original sensor, suggesting that Cu2+@MIL91(Al:Eu) can be reused for UA detection. Detecting Trace Amount of Uric Acid and Diagnose Hyperuricuria. Realizing high selectivity toward uric acid among the simultaneous species is a very significant performance when evaluating the achievement of the sensor. Hence, interfering experiments are in progress. Figure 5 shows that when uric acid is added into the suspension of Cu2+@MIL91(Al:Eu) with prior presence of another urine chemical, the intensity change of 5D0→7FJ transition of Eu3+ (612 nm) reveals a quasi-phenomenon to that with uric acid presence 6806

DOI: 10.1021/acs.inorgchem.6b03009 Inorg. Chem. 2017, 56, 6802−6808

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Inorganic Chemistry

acid is relucent red, and the other test paper treated with low concentration uric acid is almost not fluorescence emissive. With the naked eye, we can distinguish the fluorescent colors of test papers, thus prompt it to judge whether or not suffer from hyperuricuria.

only. This result suggests that the rebound effect of uric acid for the luminescence of MIL-91(Al:Eu) is not disturbed by the simultaneous chemicals, and this shows that we can further use Cu2+@MIL-91(Al:Eu) for the detection of uric acid in urine. Before exploring the possibility of Cu2+@MIL-91(Al:Eu) composite to detect uric acid in urine, the detection limit test in aqueous solution is conducted. It is observed that the luminescence intensity of in Cu2+@MIL-91(Al:Eu) at 612 nm is gradually increased with increasing uric acid concentration. We fit the linear relationship between the fluorescence intensity (612 nm) of Cu2+@MIL-91(Al:Eu) versus the content of uric acid (Figure 6a) and find a well linear relationship (R = 0.991) between the intensity ratios of 5D0→7FJ transition (I0/I) and the logarithm of uric acid concentration over the range from 10 to 1200 μmol L−1 (I0/I = 0.472−0.11 lg[UA], where [UA] is the concentration of uric acid, and the values I and I0 are the emission intensity of the suspension with/without addition of uric acid, respectively.) The limit of detection (LOD) is calculated as 1.6 μmol L−1 according to the 3σ IUPAC criteria, indicating the method is suitable and reliable. Moreover, we list the detecting performance that includes linear ranges and LOD values of different sensor systems for the detection of uric acid in Table 1. By comparing different reported sensors, the wide

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CONCLUSIONS In summary, we prepare a phosphonate MOFs MIL-91(Al:Eu) with excellent stability and outstanding luminescence. With incorporation of Cu2+, the luminescence of Eu3+ is quenched, and it will be rebounded in the presence of uric acid. This On− Off−On pattern of emission of Eu3+ is due to the coordination between metal ions with uric acid. Inspired by this pattern, the Cu2+@MIL-91(Al:Eu) composite was prepared and used for detecting uric acid. Among different species in the urine, Cu2+@MIL-91(Al:Eu) displays high selectivity and low LOD value. Moreover, the good structure and fluorescence stability of Cu2+@MIL-91(Al:Eu) are further confirmed; it is suggested that the composite is a promising fluorescent sensor to detect uric acid in urine. In addition, to examine the potential of Cu2+@MIL-91(Al:Eu) for rapid diagnosis of hyperuricuria, the practical detection of abnormal levels of uric acid in real urine is conducted. The results show that the composite powders and test paper can be rapid observational judging hyperuricuria.

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Table 1. Performance of Different Sensor Systems for Detection of UA sensor system

linear range (μM)

LOD (μM)

ref

NaYF4:Yb3+, Tm3+ NaYF4:Yb3+, Er3+, Tm3+ uricase/HRP-CdS QDs AuNCs N-MWCNTs/PtNPs xerogel-based materials Cu2+@MIL-91(Al:Eu)

20−850 10−1000 125−1000 10−800 49−313 100−700 10−1200

6.7 2.86 125 6.6 2.1