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Luminescent mixed-crystal Ln-MOF thin film for the recognition and detection of pharmaceuticals
Accepted Manuscript Title: Luminescent Mixed-Crystal Ln-MOF Thin Film for the Recognition and Detection of Pharmaceuticals Authors: Yanxin Gao, Gang Yu, Kai Liu, Bin Wang PII: DOI: Reference:
S0925-4005(17)32096-8 https://doi.org/10.1016/j.snb.2017.10.180 SNB 23484
To appear in:
Sensors and Actuators B
Received date: Revised date: Accepted date:
5-6-2017 28-10-2017 30-10-2017
Please cite this article as: Yanxin Gao, Gang Yu, Kai Liu, Bin Wang, Luminescent Mixed-Crystal Ln-MOF Thin Film for the Recognition and Detection of Pharmaceuticals, Sensors and Actuators B: Chemical https://doi.org/10.1016/j.snb.2017.10.180 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Luminescent Mixed-Crystal Ln-MOF Thin Film for the Recognition and Detection of Pharmaceuticals
Yanxin Gaoa, Gang Yu*a, Kai Liub, Bin Wanga
a School of Environment, Beijing Key Laboratory for Emerging Organic Contaminants Control, State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), Tsinghua University, Beijing 100084, China b Line and Robinson Laboratory Rm 227, California Institute of Technology, 1200 E California Blvd, CA 91125, USA
* Corresponding author. Tel.: +86 10 62787137; fax: +86 10 62794006. E-mail: [email protected]
Graphical abstract
1
Highlights
A series of mixed-crystal Ln-MOFs were successfully synthesized.
MLMOF-3 was selected and fabricated to form thin film.
MLMOF-3 thin film can recognize pharmaceuticals by different intensity ratios.
The intensity ratio was linearly correlate to the concentration of pharmaceuticals.
Abstract
2
The development of simple and reliable methods for recognition and detection of pharmaceuticals has been a matter of great concern. In this work, a series of mixed-crystal lanthanide metal-organic frameworks (Ln-MOFs) were synthesized by solvothermal method. Among them, MLMOF-3 was selected and fabricated to form nanoscale crystals and prepare luminescent Ln-MOF thin film. The different changes of emission intensity ratio of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 7F5 (Tb3+, 547 nm) transitions depending on the guest molecules enabled MLMOF-3 film to recognize different pharmaceutical molecules. Moreover, the intensity ratio was observed to linearly correlate to the concentration of pharmaceuticals. Compared to the traditional absolute emission intensity method based on single lanthanide ions, mixed-crystal Ln-MOF thin film generated more stable and accurate luminescent signals, which is an excellent candidate of self-referencing and self-calibrating luminescent sensor for various applications.
Key words: Ln-MOFs; thin film; recognition; detection; pharmaceuticals There has been extensive interest in recognition and detection of pharmaceuticals due to their important roles in biological and environmental systems [1]. However, to date the detection of pharmaceuticals is limited because of expensive devices and complicated procedures, such as liquid chromatography with UV detection, mass spectrometry, LC-tandem mass spectrometry, and capillary electrophoresis [2-5]. Alternately, optical sensing has been considered as a promising technique as it could offer sensitive, facile, and fast assays. The main challenge of developing optical method lies in the selection of sensing material. Metal-organic frameworks (MOFs), with unusual optical, magnetic or electronic properties, has provided a broad perspective for utility in smart sensors [6-9]. Lanthanide MOFs (Ln-MOFs) have attracted special attention due to the unusual coordination characteristics and exceptional luminescent properties. Firstly, lanthanide (Ln) ions have unique photo-electronic properties arising from the 4f electrons, including large absorption and emission energy gaps, sharp and stable emission bands, and long luminescence lifetimes [10-12]. Secondly, the introduction of suitable organic linkers into Ln-MOFs will greatly enhance their light absorption ability and increase the luminescent brightness by “antenna effect” [11]. In fact, some Ln-MOFs have already 3
been used as luminescent indicator for metal ions, anions and small molecules, demonstrating that they are efficient sensor materials [13-15]. However, there is still much room for improvement in the current research. As most Ln-MOFs are based on the change of absolute emission intensity of single lanthanide ion, they are not accurate enough and lack the ability of differentiating multiple molecules [16]. Recent elaborations indicate that the sensing performance can be improved by changing the ratios of lanthanide ions in mixed-crystal Ln-MOFs [17]. Compared to other sensors that contain only one luminescent site, the mixed-crystal Ln-MOFs with self-referring strategy can amplify the relative emission ratios, which would enlarge the luminescent signals and make decoding molecules easily realized. In addition, researchers usually used random and disarranged polycrystalline powders for sensing, while another type of MOF-based device, substrates supporting MOF thin films remain relatively understudied [18-22]. MOF thin films grown on a solid substrate offer a number of advantages over powder samples. They are easily separated from the liquid medium; the number of defects and grain boundaries is significantly reduced in the highly oriented quasi-epitaxial layers; and the number of binding sites at the outer surface of the MOF film is constant and does not depend on MOF film thickness [18, 23]. Considering the above two points, mixed-crystal Ln-MOF thin film is likely to offer an opportunity for high-sensitivity chemical sensing. Herein we reported a luminescent mixed-crystal Ln-MOF thin film for the sensing of pharmaceuticals. The monodisperse crystals of mixed Ln-MOFs were fabricated by sodium acetate and dip-coated on Indium-Tin Oxide (ITO) glass to prepare large scale, uniform and continuous thin film (scheme 1). The unique luminescent properties enabled the film to recognize pharmaceuticals as “fast screening” by different intensity ratio changes. Then the quantitative detection of pharmaceuticals was further investigated. To the best of our knowledge, there has been no report on the applications of mixed-crystal Ln-MOF thin film. This work is the first attempt to use mixed-crystal Ln-MOF thin film as a luminescent indicator for the detection of pharmaceuticals. The X-Ray Diffraction (XRD) patterns of the nanocrystal Ln-MOFs after fabrication are identical to the simulated pattern, indicating that the structure is kept (Fig. S1). The 4
morphology of the mixed-crystals was observed by scanning electron microscope (SEM) in details. As shown in Fig. S2, the crystals display elongated hexagonal morphology of about 150±50 nm. From Fig. S3, it can be seen that the excitation spectra both consist of a broad band in the range from 200 to 300 nm with maxima at about 285 nm, because of the charge-transfer band between the O 2− and Ln3+ ions. The results indicate that the energy was efficiently transferred from the organic ligand to lanthanide cations via “antenna effect” [24-25]. Tb-BTC shows the characteristic transitions of Tb 3+ ions such as 5D4 → 7F6 (489 nm), 5D4 →7F5 (547 nm), 5D4 → 7F4 (587 nm), and 5D4 → 7F3 (622 nm) in the luminescence spectra, while Eu-BTC exhibits the characteristic transitions of Eu 3+ ions like 5D
0
→ 7F1 (592 nm),5D0 → 7F2 (619 nm), 5D0 → 7F3 (654 nm), and 5D0 → 7F4 (703 nm).
Structural analysis reveals that six carboxyl groups and a terminal water ligand bind each Ln ion, while each rod is connected to four neighboring rods through the benzene ring of the BTC link (Fig. S4). Varying the ratios of Tb 3+ to Eu3+ ions during the synthesis process resulted in mixed-crystal Ln-MOFs: Eu0.01Tb0.99-BTC (MLMOF-1), Eu0.05Tb0.95-BTC
(MLMOF-2),
Eu0.1Tb0.9-BTC
(MLMOF-3),
Eu0.15Tb0.85-BTC
(MLMOF-4), and Eu0.2Tb0.8-BTC (MLMOF-5). As shown in Fig. 1a, in the spectrum of MLMOF-3 the two characteristic peaks of 5D4 → 7F5 (Tb3+, 547 nm) and 5D0→7F2 (Eu3+, 619 nm) were comparable, thereby it was selected to prepare the mixed-crystal Ln-MOF thin film for sensing pharmaceuticals. Table 1 shows EDS analysis for MLMOF-3 thin film. Fig. 1b shows that the XRD patterns of the ITO glass-supported MLMOF-3 film are identical to the simulated pattern, which demonstrate the homogeneity and purity of the constructed crystalline film. The photograph exhibited in Fig. 1c illustrates the ITO glass acts as uniform support allowing the film to form continuously, and the surface is smooth and defect-free over a large area. The cross-section view (Fig. 1d) shows the film has a thickness of 4-5 μm. Furthermore, to investigate the effect of environmental samples, MLMOF-3 thin film was tested under different pH conditions with deionized water and placed in different solutions such as pure water, river water, saline and simulated body fluid. The results show the emission intensity ratio of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 5
7
F5 (Tb3+, 547 nm) transitions did not change significantly either in the pH range (4-9) or in
different environmental samples (Fig. S5). Encouraged by the luminescent property of the mixed-crystal Ln-MOFs, we expected that MLMOF-3 film would exhibit guest-dependent luminescence via different host-guest interactions and thereby realize their applications in sensing pharmaceuticals. The film was placed in solution containing 0.1 mM different pharmaceuticals (antipyrine, benzafibrate, caffeine, clofibrate, clotetracycline, coumarin, diclofenac, fluorouracil, nalidixic acid, naproxen, sulfachinoxalin, and tetracycline) before the luminescence studies. These pharmaceuticals themselves show no luminescence (Fig. S6). However, as shown in Fig. 2a, the emission intensity of MLMOF-3 film is largely dependent on the pharmaceutical molecule. The emission intensity ratios of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 7F5 (Tb3+, 547 nm) transitions in the luminescence spectra of MLMOF-3 film were used to calculate the intensity ratio change by (R-R0)/R0, where R0 is the initial intensity ratio without analyte and R is the intensity ratio in the presence of analyte. It was remarkable that these pharmaceuticals were clearly discriminated from one another by the value of (R-R0)/R0 (Fig. 2b). For example, benzafibrate exhibits a significant enhancing effect for the emission of Tb3+ ions and a 69% decrease of the intensity ratio is observed, while coumarin mainly enhances the emission of Eu3+ ions and the value increases 271%. Moreover, MLMOF-3 film emits different guest-dependent light colors (Fig. 2c), which can be intuitively distinguished by the naked eye. The colors match well with the calculated chromaticity coordinates on the base of chromaticity diagram developed by the Commission Internationale de L'Eclairage in 1931 (Fig. 2d). Although chlortetracycline and tetracycline have very similar structures, chlortetracycline has another functional group -Cl. The results demonstrated that -Cl enhanced the emission intensity of Tb 3+ ions and led to the lower emission intensity ratio of MZMOF-3 film. So the recognition of similar molecules can be realized as well. These results suggest that the adsorbed molecules not only can modulate the energy transfer efficiency from “antenna” organic species to Eu3+ and Tb3+ ions but also are able to adjust the energy allocation between Eu 3+ and Tb3+ ions by the host-guest interactions, 6
enhancing the emission of one Ln 3+ ion and quenching the emission of another in the luminescence spectra of MLMOF-3 film [16]. We presume that the different functional groups and structures of pharmaceutical molecules generate different hydrogen-bonding and/or hydrophobic interactions, which might affect their affinity for MLMOF-3 and lead to the different energy transfer mechanism. For example, the decreased intensity of 5D4 → 7
F5 (Tb3+, 547 nm) transition and the increased intensity of 5D0 → 7F2 (Eu3+, 619 nm)
induced by energy transfer from Tb 3+ to Eu3+ were significantly enhanced in the presence of coumarin. The lifetime of MLMOF-3 was monitored at 547 and 619 nm (Fig. S7). The luminescent lifetime of 5D4 → 7F5 (τTb, 547 nm) is reduced by the addition of coumarin (0.1 mM), while the 5D0 → 7F2 (τEu, 619 nm) lifetime increases (Table S2). The result is consistent with an energy-transfer mechanism from Tb 3+ to Eu3+ in the presence of coumarin and hence the overall effect is compound specific. The effect of addition of sulfameter, penicillin, and fluoxetine on coumarin emission spectra is insignificant due to the fact that coumarin has higher binding energy and lower steric hindrance, and hence it is easier to occupy the binding sites of Ln-MOFs.
According to the XRD patterns of
pharmaceutical included film, the peaks are slightly shifted depending on the adsorbed molecules (Fig. S8). When these samples were washed by methanol and dried, the peaks in XRD patterns are identical to those of the as-synthesized one, which confirms the reversible property of MLMOF-3 film. Moreover, in the recycling experiments, the probing of coumarin by MLMOF-3 film was still efficient after 5 cycles (Fig. S9). In order to investigate the quantitative relationship between concentration and intensity ratio of MLMOF-3, we chose coumarin and caffeine as target compounds. The plot reveals that in the range of 1-100 μM, a good linear relationship was retained between (R-R0)/R0 and the concentration of coumarin with a slope of about 0.0276±0.0006, indicating that MLMOF-3 is a self-referencing fluorescent sensor. Accordingly, the emission intensity ratio of MLMOF-3 film is quantitive in the concentration range from 1-100 μM. The calculation of detection limit showed the detection limit for coumarin was about 0.34 μg/mL (2.3 μM) (S2. Detection Limit). With the increase in concentration the 7
observed emission colors of MLMOF-3 film gradually become red, matching well with the calculated chromaticity coordinates (Fig. S10). Moreover, luminescence quantitative experiment was also performed with 1-100 μM caffeine. The slope obtained from the curve is -0.0045±0.0002 and the color changes from orange to yellowish green, as shown in Fig. S10. We also tested the values of (R-R0)/R0 in simulated samples. The results show that the data obtained from simulated samples are basically consistent with the detection curves, indicating that MLMOF-3 is feasible in practical applications (Fig. S11). Compared to other Ln-MOF sensors that contain only one kind of Ln 3+ cations, such a self-referring strategy amplified the relative emission ratios, which would also enlarge the luminescent signals and make the recognition and detection of pharmaceuticals be easily realized. It is apparent that using integrated intensity changes of mixed-crystal Ln-MOF film is more reliable than the absolute emission intensity method in detection, since the powder emission intensities have lots of uncontrolled errors [16]. Further, as relative intensity is used in this work, (R-R0)/R0 is independent of the amount of MLMOF-3 with the only correlation being pharmaceutical concentration. MLMOF-3 film does not need additional calibration of luminescence intensity and therefore is a self-calibrating luminescent sensor. In conclusion, isostructural mixed-crystal MLMOFs were synthesized by varying the molar ratios of Tb3+ to Eu3+ and MLMOF-3 was selected. Such homogeneous mixed Ln-MOF could be fabricated by sodium acetate and used to prepare the mixed-crystal Ln-MOF thin film (S1. Experimental Section). The different luminescence depending on the guest molecules enabled MLMOF-3 film to be an excellent candidate of self-referencing and self-calibrating luminescent sensor by the fingerprint correlation between each different pharmaceutical molecule and the emission intensity change. The intensity ratio was observed to linearly correlate to the concentration of pharmaceuticals in a certain range. These results suggest a new pharmaceutical detecting method based on the luminescent mixed-crystal Ln-MOF film and may motivate the development of versatile luminescent Ln-MOF sensors for other sensing applications.
8
Acknowledgements This study was supported by the National High Technology Research and Development Program of China (2013AA06A305), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1261), and the Collaborative Innovation Center for Regional Environmental Quality.
References [1] J.L. Liu and M.H. Wong, Pharmaceuticals and personal care products (PPCPs): A review on environmental contamination in China, Environ. Int. (2013) 208-224. [2] D. Moreno-González, F.J. Lara, N. Jurgovská, L. Gámiz-Gracia and A.M. García-Campaña, Determination of aminoglycosides in honey by capillary electrophoresis tandem mass spectrometry and extraction with molecularly imprinted polymers, Anal. Chem. Acta. (2015) 321-328. [3] C. Blasco, A.D. Corcia and Y. Picó, Determination of tetracyclines in multi-specie animal tissues by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry, Food Chem. 4 (2009) 1005-1012. [4] K. Håkansson, R.V. Coorey, R.A. Zubarev, V.L. Talrose and P. Håkansson, Low-mass ions observed in plasma desorption mass spectrometry of high explosives, J. Mass. Spectrom. 3 (2000) 337-346. [5] E. Benito-Peña, J.L. Urraca and M.C. Moreno-Bondi, Quantitative determination of penicillin V and amoxicillin in feed samples by pressurised liquid extraction and liquid chromatography with ultraviolet detection, Journal of Pharmaceutical & Biomedical Analysis 2 (2009) 289-294. [6] J.P. Ma, Y. Yu and Y.B. Dong, Fluorene-based Cu(II)-MOF: a visual colorimetric anion sensor and separator based on an anion-exchange approach, Chem. Commun. 24 (2012) 2946. [7] W. Liu, X. Dai, Z. Bai, Y. Wang, Z. Yang, L. Zhang, L. Xu, L. Chen, Y. Li, D. Gui, J. Diwu, J. Wang, R. Zhou, Z. Chai and S. Wang, Highly Sensitive and Selective Uranium Detection in Natural Water Systems Using a Luminescent Mesoporous Metal-Organic Framework Equipped with Abundant Lewis Basic Sites: A Combined Batch, X-ray Absorption Spectroscopy, and First Principles Simulation Investigation., Environ. Sci. Technol. (2017) 3911-3921. [8] J.M. Zhou, W. Shi, N. Xu and P. Cheng, Highly selective luminescent sensing of fluoride and organic small-molecule pollutants based on novel lanthanide metal-organic frameworks., Inorg. Chem. 14 (2013) 8082-8090. [9] L. Chun-Sen, S. Chun-Xiao, T. Jia-Yue, W. Zhuo-Wei, J. Hong-Fei, S. Ying-Pan, Z. Shuai, Z. Zhi-Hong, H. Ling-Hao and D. Miao, Highly stable aluminum-based metal-organic frameworks as biosensing platforms for assessment of food safety, Biosensors and Bioelectronics (2017) 804-810. [10] Y.J. Cui, B.L. Chen and G.D. Qian, Lanthanide metal-organic frameworks for luminescent sensing 9
and light-emitting applications, Coordin. Chem. Rev. SI (2014) 76-86. [11] S. Eliseeva and J.C.G. Buenzli, ChemInform Abstract: Lanthanide Luminescence for Functional Materials and Bio-Sciences, Chem. Soc. Rev. 1 (2010) 189-227. [12] E.G. Moore, A. Samuel and K.N. Raymond, From Antenna to Assay: Lessons Learned in Lanthanide Luminescence, Accounts Chem. Res. 4 (2009) 542-552. [13] J. Hao and B. Yan, Determination of Urinary 1-Hydroxypyrene for Biomonitoring of Human Exposure to Polycyclic Aromatic Hydrocarbons Carcinogens by a Lanthanide-functionalized Metal-Organic Framework Sensor, Adv. Funct. Mater. 6 (2017) 1603856. [14] Z. Wang, H. Liu, S. Wang, Z. Rao and Y. Yang, A luminescent Terbium-Succinate MOF thin film fabricated by electrodeposition for sensing of Cu2+ in aqueous environment, Sensor Actuat. B-Chem. (2015) 779-787. [15] Y. Chen and S. Ma, Microporous lanthanide metal-organic frameworks, Rev. Inorg. Chem. 2-4 (2012) 81-100. [16] C. Zhan, S. Ou, C. Zou, M. Zhao and C.D. Wu, A Luminescent Mixed-Lanthanide-Organic Framework Sensor for Decoding Different Volatile Organic Molecules, Anal. Chem. 13 (2014) 6648-6653. [17] S.Y. Zhang, W. Shi, P. Cheng and M.J. Zaworotko, A mixed-crystal lanthanide zeolite-like metal-organic framework as a fluorescent indicator for lysophosphatidic acid, a cancer biomarker., J Am. Chem. Soc. 38 (2015) 12203. [18] O. Shekhah, J. Liu, R.A. Fischer and W. Ch, MOF thin films: existing and future applications., Chem. Soc. Rev. 2 (2011) 1081. [19] Z. Dou, J. Yu, H. Xu, Y. Cui, Y. Yang and G. Qian, Preparation and thiols sensing of luminescent metal-organic framework films functionalized with lanthanide ions, Microporous & Mesoporous Materials 13 (2013) 198-204. [20] K.K. Tanabe and S.M. Cohen, Postsynthetic modification of metal-organic frameworks-a progress report, Chem. Soc. Rev. 2 (2011) 498-519. [21] S.M. Yoon, J.H. Park and B.A. Grzybowski, Large-Area, Freestanding MOF Films of Planar, Curvilinear, or Micropatterned Topographies, Angew. Chem. Int. Edit. 1 (2017) 127-132. [22] Z.H. Wang, H.P. Liu, S.Y. Wang, Z.L. Rao and Y.Y. Yang, A luminescent Terbium-Succinate MOF thin film fabricated by electrodeposition for sensing of Cu2+ in aqueous environment, Sensor Actuat. B-Chem. (2015) 779-787. [23] S. Bordiga, L. Regli, F. Bonino, E. Groppo, C. Lamberti, B. Xiao, P.S. Wheatley, R.E. Morris and A. Zecchina, Adsorption properties of HKUST-1 toward hydrogen and other small molecules monitored by IR, Phys. Chem. 21 (2007) 2676. [24] B. Chen, L. Wang, Y. Xiao, F.R. Fronczek, M. Xue, Y. Cui and G. Qian, A Luminescent Metal–Organic Framework with Lewis Basic Pyridyl Sites for the Sensing of Metal Ions, Angewandte Chemie (2009) 508-511. [25] M.J. Dong, M. Zhao, S. Ou, C. Zou, Prof. X and Dr. C. Wu, A Luminescent Dye@MOF Platform: Emission Fingerprint Relationships of Volatile Organic Molecules, Angew. Chem. Int. Edit. (2014) 10
1575-1579.
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Figures
Fig. 1 (a) Emission spectra of EuxTb1-x-BTC ( λex = 287 nm); (b) XRD spectrum of Ln-MOF thin film; SEM image of (c) surface and (d) cross section of the film Fig. 2 (a) The emission spectra, (b) the emission intensity ratio changes, (c) the optical photographs and (d) CIE chromaticity coordinates of Ln-MOF thin film in the presence of different analytes. (20 mL 10-4 M) Fig. 3 Intensity ratio changes of Ln-MOF thin film in the presence of different concentrations of coumarin/caffeine Scheme 1. Preparation process of mixed-crystal Ln-MOF thin film
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S0925-4005(17)32096-8 https://doi.org/10.1016/j.snb.2017.10.180 SNB 23484
To appear in:
Sensors and Actuators B
Received date: Revised date: Accepted date:
5-6-2017 28-10-2017 30-10-2017
Please cite this article as: Yanxin Gao, Gang Yu, Kai Liu, Bin Wang, Luminescent Mixed-Crystal Ln-MOF Thin Film for the Recognition and Detection of Pharmaceuticals, Sensors and Actuators B: Chemical https://doi.org/10.1016/j.snb.2017.10.180 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Luminescent Mixed-Crystal Ln-MOF Thin Film for the Recognition and Detection of Pharmaceuticals
Yanxin Gaoa, Gang Yu*a, Kai Liub, Bin Wanga
a School of Environment, Beijing Key Laboratory for Emerging Organic Contaminants Control, State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), Tsinghua University, Beijing 100084, China b Line and Robinson Laboratory Rm 227, California Institute of Technology, 1200 E California Blvd, CA 91125, USA
* Corresponding author. Tel.: +86 10 62787137; fax: +86 10 62794006. E-mail: [email protected]
Graphical abstract
1
Highlights
A series of mixed-crystal Ln-MOFs were successfully synthesized.
MLMOF-3 was selected and fabricated to form thin film.
MLMOF-3 thin film can recognize pharmaceuticals by different intensity ratios.
The intensity ratio was linearly correlate to the concentration of pharmaceuticals.
Abstract
2
The development of simple and reliable methods for recognition and detection of pharmaceuticals has been a matter of great concern. In this work, a series of mixed-crystal lanthanide metal-organic frameworks (Ln-MOFs) were synthesized by solvothermal method. Among them, MLMOF-3 was selected and fabricated to form nanoscale crystals and prepare luminescent Ln-MOF thin film. The different changes of emission intensity ratio of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 7F5 (Tb3+, 547 nm) transitions depending on the guest molecules enabled MLMOF-3 film to recognize different pharmaceutical molecules. Moreover, the intensity ratio was observed to linearly correlate to the concentration of pharmaceuticals. Compared to the traditional absolute emission intensity method based on single lanthanide ions, mixed-crystal Ln-MOF thin film generated more stable and accurate luminescent signals, which is an excellent candidate of self-referencing and self-calibrating luminescent sensor for various applications.
Key words: Ln-MOFs; thin film; recognition; detection; pharmaceuticals There has been extensive interest in recognition and detection of pharmaceuticals due to their important roles in biological and environmental systems [1]. However, to date the detection of pharmaceuticals is limited because of expensive devices and complicated procedures, such as liquid chromatography with UV detection, mass spectrometry, LC-tandem mass spectrometry, and capillary electrophoresis [2-5]. Alternately, optical sensing has been considered as a promising technique as it could offer sensitive, facile, and fast assays. The main challenge of developing optical method lies in the selection of sensing material. Metal-organic frameworks (MOFs), with unusual optical, magnetic or electronic properties, has provided a broad perspective for utility in smart sensors [6-9]. Lanthanide MOFs (Ln-MOFs) have attracted special attention due to the unusual coordination characteristics and exceptional luminescent properties. Firstly, lanthanide (Ln) ions have unique photo-electronic properties arising from the 4f electrons, including large absorption and emission energy gaps, sharp and stable emission bands, and long luminescence lifetimes [10-12]. Secondly, the introduction of suitable organic linkers into Ln-MOFs will greatly enhance their light absorption ability and increase the luminescent brightness by “antenna effect” [11]. In fact, some Ln-MOFs have already 3
been used as luminescent indicator for metal ions, anions and small molecules, demonstrating that they are efficient sensor materials [13-15]. However, there is still much room for improvement in the current research. As most Ln-MOFs are based on the change of absolute emission intensity of single lanthanide ion, they are not accurate enough and lack the ability of differentiating multiple molecules [16]. Recent elaborations indicate that the sensing performance can be improved by changing the ratios of lanthanide ions in mixed-crystal Ln-MOFs [17]. Compared to other sensors that contain only one luminescent site, the mixed-crystal Ln-MOFs with self-referring strategy can amplify the relative emission ratios, which would enlarge the luminescent signals and make decoding molecules easily realized. In addition, researchers usually used random and disarranged polycrystalline powders for sensing, while another type of MOF-based device, substrates supporting MOF thin films remain relatively understudied [18-22]. MOF thin films grown on a solid substrate offer a number of advantages over powder samples. They are easily separated from the liquid medium; the number of defects and grain boundaries is significantly reduced in the highly oriented quasi-epitaxial layers; and the number of binding sites at the outer surface of the MOF film is constant and does not depend on MOF film thickness [18, 23]. Considering the above two points, mixed-crystal Ln-MOF thin film is likely to offer an opportunity for high-sensitivity chemical sensing. Herein we reported a luminescent mixed-crystal Ln-MOF thin film for the sensing of pharmaceuticals. The monodisperse crystals of mixed Ln-MOFs were fabricated by sodium acetate and dip-coated on Indium-Tin Oxide (ITO) glass to prepare large scale, uniform and continuous thin film (scheme 1). The unique luminescent properties enabled the film to recognize pharmaceuticals as “fast screening” by different intensity ratio changes. Then the quantitative detection of pharmaceuticals was further investigated. To the best of our knowledge, there has been no report on the applications of mixed-crystal Ln-MOF thin film. This work is the first attempt to use mixed-crystal Ln-MOF thin film as a luminescent indicator for the detection of pharmaceuticals. The X-Ray Diffraction (XRD) patterns of the nanocrystal Ln-MOFs after fabrication are identical to the simulated pattern, indicating that the structure is kept (Fig. S1). The 4
morphology of the mixed-crystals was observed by scanning electron microscope (SEM) in details. As shown in Fig. S2, the crystals display elongated hexagonal morphology of about 150±50 nm. From Fig. S3, it can be seen that the excitation spectra both consist of a broad band in the range from 200 to 300 nm with maxima at about 285 nm, because of the charge-transfer band between the O 2− and Ln3+ ions. The results indicate that the energy was efficiently transferred from the organic ligand to lanthanide cations via “antenna effect” [24-25]. Tb-BTC shows the characteristic transitions of Tb 3+ ions such as 5D4 → 7F6 (489 nm), 5D4 →7F5 (547 nm), 5D4 → 7F4 (587 nm), and 5D4 → 7F3 (622 nm) in the luminescence spectra, while Eu-BTC exhibits the characteristic transitions of Eu 3+ ions like 5D
0
→ 7F1 (592 nm),5D0 → 7F2 (619 nm), 5D0 → 7F3 (654 nm), and 5D0 → 7F4 (703 nm).
Structural analysis reveals that six carboxyl groups and a terminal water ligand bind each Ln ion, while each rod is connected to four neighboring rods through the benzene ring of the BTC link (Fig. S4). Varying the ratios of Tb 3+ to Eu3+ ions during the synthesis process resulted in mixed-crystal Ln-MOFs: Eu0.01Tb0.99-BTC (MLMOF-1), Eu0.05Tb0.95-BTC
(MLMOF-2),
Eu0.1Tb0.9-BTC
(MLMOF-3),
Eu0.15Tb0.85-BTC
(MLMOF-4), and Eu0.2Tb0.8-BTC (MLMOF-5). As shown in Fig. 1a, in the spectrum of MLMOF-3 the two characteristic peaks of 5D4 → 7F5 (Tb3+, 547 nm) and 5D0→7F2 (Eu3+, 619 nm) were comparable, thereby it was selected to prepare the mixed-crystal Ln-MOF thin film for sensing pharmaceuticals. Table 1 shows EDS analysis for MLMOF-3 thin film. Fig. 1b shows that the XRD patterns of the ITO glass-supported MLMOF-3 film are identical to the simulated pattern, which demonstrate the homogeneity and purity of the constructed crystalline film. The photograph exhibited in Fig. 1c illustrates the ITO glass acts as uniform support allowing the film to form continuously, and the surface is smooth and defect-free over a large area. The cross-section view (Fig. 1d) shows the film has a thickness of 4-5 μm. Furthermore, to investigate the effect of environmental samples, MLMOF-3 thin film was tested under different pH conditions with deionized water and placed in different solutions such as pure water, river water, saline and simulated body fluid. The results show the emission intensity ratio of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 5
7
F5 (Tb3+, 547 nm) transitions did not change significantly either in the pH range (4-9) or in
different environmental samples (Fig. S5). Encouraged by the luminescent property of the mixed-crystal Ln-MOFs, we expected that MLMOF-3 film would exhibit guest-dependent luminescence via different host-guest interactions and thereby realize their applications in sensing pharmaceuticals. The film was placed in solution containing 0.1 mM different pharmaceuticals (antipyrine, benzafibrate, caffeine, clofibrate, clotetracycline, coumarin, diclofenac, fluorouracil, nalidixic acid, naproxen, sulfachinoxalin, and tetracycline) before the luminescence studies. These pharmaceuticals themselves show no luminescence (Fig. S6). However, as shown in Fig. 2a, the emission intensity of MLMOF-3 film is largely dependent on the pharmaceutical molecule. The emission intensity ratios of 5D0 → 7F2 (Eu3+, 619 nm) to 5D4 → 7F5 (Tb3+, 547 nm) transitions in the luminescence spectra of MLMOF-3 film were used to calculate the intensity ratio change by (R-R0)/R0, where R0 is the initial intensity ratio without analyte and R is the intensity ratio in the presence of analyte. It was remarkable that these pharmaceuticals were clearly discriminated from one another by the value of (R-R0)/R0 (Fig. 2b). For example, benzafibrate exhibits a significant enhancing effect for the emission of Tb3+ ions and a 69% decrease of the intensity ratio is observed, while coumarin mainly enhances the emission of Eu3+ ions and the value increases 271%. Moreover, MLMOF-3 film emits different guest-dependent light colors (Fig. 2c), which can be intuitively distinguished by the naked eye. The colors match well with the calculated chromaticity coordinates on the base of chromaticity diagram developed by the Commission Internationale de L'Eclairage in 1931 (Fig. 2d). Although chlortetracycline and tetracycline have very similar structures, chlortetracycline has another functional group -Cl. The results demonstrated that -Cl enhanced the emission intensity of Tb 3+ ions and led to the lower emission intensity ratio of MZMOF-3 film. So the recognition of similar molecules can be realized as well. These results suggest that the adsorbed molecules not only can modulate the energy transfer efficiency from “antenna” organic species to Eu3+ and Tb3+ ions but also are able to adjust the energy allocation between Eu 3+ and Tb3+ ions by the host-guest interactions, 6
enhancing the emission of one Ln 3+ ion and quenching the emission of another in the luminescence spectra of MLMOF-3 film [16]. We presume that the different functional groups and structures of pharmaceutical molecules generate different hydrogen-bonding and/or hydrophobic interactions, which might affect their affinity for MLMOF-3 and lead to the different energy transfer mechanism. For example, the decreased intensity of 5D4 → 7
F5 (Tb3+, 547 nm) transition and the increased intensity of 5D0 → 7F2 (Eu3+, 619 nm)
induced by energy transfer from Tb 3+ to Eu3+ were significantly enhanced in the presence of coumarin. The lifetime of MLMOF-3 was monitored at 547 and 619 nm (Fig. S7). The luminescent lifetime of 5D4 → 7F5 (τTb, 547 nm) is reduced by the addition of coumarin (0.1 mM), while the 5D0 → 7F2 (τEu, 619 nm) lifetime increases (Table S2). The result is consistent with an energy-transfer mechanism from Tb 3+ to Eu3+ in the presence of coumarin and hence the overall effect is compound specific. The effect of addition of sulfameter, penicillin, and fluoxetine on coumarin emission spectra is insignificant due to the fact that coumarin has higher binding energy and lower steric hindrance, and hence it is easier to occupy the binding sites of Ln-MOFs.
According to the XRD patterns of
pharmaceutical included film, the peaks are slightly shifted depending on the adsorbed molecules (Fig. S8). When these samples were washed by methanol and dried, the peaks in XRD patterns are identical to those of the as-synthesized one, which confirms the reversible property of MLMOF-3 film. Moreover, in the recycling experiments, the probing of coumarin by MLMOF-3 film was still efficient after 5 cycles (Fig. S9). In order to investigate the quantitative relationship between concentration and intensity ratio of MLMOF-3, we chose coumarin and caffeine as target compounds. The plot reveals that in the range of 1-100 μM, a good linear relationship was retained between (R-R0)/R0 and the concentration of coumarin with a slope of about 0.0276±0.0006, indicating that MLMOF-3 is a self-referencing fluorescent sensor. Accordingly, the emission intensity ratio of MLMOF-3 film is quantitive in the concentration range from 1-100 μM. The calculation of detection limit showed the detection limit for coumarin was about 0.34 μg/mL (2.3 μM) (S2. Detection Limit). With the increase in concentration the 7
observed emission colors of MLMOF-3 film gradually become red, matching well with the calculated chromaticity coordinates (Fig. S10). Moreover, luminescence quantitative experiment was also performed with 1-100 μM caffeine. The slope obtained from the curve is -0.0045±0.0002 and the color changes from orange to yellowish green, as shown in Fig. S10. We also tested the values of (R-R0)/R0 in simulated samples. The results show that the data obtained from simulated samples are basically consistent with the detection curves, indicating that MLMOF-3 is feasible in practical applications (Fig. S11). Compared to other Ln-MOF sensors that contain only one kind of Ln 3+ cations, such a self-referring strategy amplified the relative emission ratios, which would also enlarge the luminescent signals and make the recognition and detection of pharmaceuticals be easily realized. It is apparent that using integrated intensity changes of mixed-crystal Ln-MOF film is more reliable than the absolute emission intensity method in detection, since the powder emission intensities have lots of uncontrolled errors [16]. Further, as relative intensity is used in this work, (R-R0)/R0 is independent of the amount of MLMOF-3 with the only correlation being pharmaceutical concentration. MLMOF-3 film does not need additional calibration of luminescence intensity and therefore is a self-calibrating luminescent sensor. In conclusion, isostructural mixed-crystal MLMOFs were synthesized by varying the molar ratios of Tb3+ to Eu3+ and MLMOF-3 was selected. Such homogeneous mixed Ln-MOF could be fabricated by sodium acetate and used to prepare the mixed-crystal Ln-MOF thin film (S1. Experimental Section). The different luminescence depending on the guest molecules enabled MLMOF-3 film to be an excellent candidate of self-referencing and self-calibrating luminescent sensor by the fingerprint correlation between each different pharmaceutical molecule and the emission intensity change. The intensity ratio was observed to linearly correlate to the concentration of pharmaceuticals in a certain range. These results suggest a new pharmaceutical detecting method based on the luminescent mixed-crystal Ln-MOF film and may motivate the development of versatile luminescent Ln-MOF sensors for other sensing applications.
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Acknowledgements This study was supported by the National High Technology Research and Development Program of China (2013AA06A305), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1261), and the Collaborative Innovation Center for Regional Environmental Quality.
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Figures
Fig. 1 (a) Emission spectra of EuxTb1-x-BTC ( λex = 287 nm); (b) XRD spectrum of Ln-MOF thin film; SEM image of (c) surface and (d) cross section of the film Fig. 2 (a) The emission spectra, (b) the emission intensity ratio changes, (c) the optical photographs and (d) CIE chromaticity coordinates of Ln-MOF thin film in the presence of different analytes. (20 mL 10-4 M) Fig. 3 Intensity ratio changes of Ln-MOF thin film in the presence of different concentrations of coumarin/caffeine Scheme 1. Preparation process of mixed-crystal Ln-MOF thin film
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