Synthesis of an MOF-based Hg2+-fluorescent probe via stepwise post-synthetic modification in a single-crystal-to-single-crystal fashion and its application in bioimaging

Wen-Yan Li, Song Yang, Yan-An Li*, Qian-Ying Li, Qun Guan and Yu-Bin Dong*
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, P. R. China. E-mail: yananli@sdnu.edu.cn; yubindong@sdnu.edu.cn

Received 10th July 2019 , Accepted 5th September 2019

First published on 5th September 2019


Although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformations. In this contribution, three new MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G′, were prepared via the single-crystal-to-single-crystal post-synthetic modification approach. For bioimaging, nanosized UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′ were also prepared. Herein, nanosized UiO-68-R6G with a rhodamine-based fluorescence switch was found to be a highly sensitive and selective fluorescent probe for the detection of Hg2+ both in vitro and in vivo.


Introduction

Highly toxic mercury, as a widespread environmental pollutant, has attracted significant concern in recent years. As is well known, mercury exists in the environment in various chemical forms such as inorganic mercury and methylmercury. As the most stable inorganic form, Hg2+ is known to be more dangerous owing to its good aqueous solubility1,2 because it can easily intrude in the human food chain via crops and water. Even at low concentrations, Hg2+ can induce severely adverse effects on the human endocrine system, nervous system, and kidneys.3,4 Therefore, the development of rapid and sensitive analytical methods for the detection of Hg2+ is highly necessary. Compared with traditional detection methods, such as atomic absorption, ultrasensitive stripping voltammetry, and inductively coupled plasma mass spectrometry, fluorescent probe-based approaches have exhibited a congenital advantage due to their high sensitivity and specificity,5–7 easy operation, and real-time monitoring.

As porous crystalline hybrid materials, metal–organic frameworks (MOFs)8 exhibit various potential applications in the fields of catalysis,9 gas storage,10 separation,11 biomedicine12 and sensing.13 Considering their inherent features such as large surface area, tunable pore size, functionalized inner and outer surfaces, and acceptable biological safety, MOFs can be an ideal platform to fabricate fluorescent probes14 for the detection of environmental pollutants, such as mercury, both in vitro and in vivo based on following reasons. First, the periodic structural feature of MOFs enables high luminophore loading but without aggregation; therefore, deleterious self-quenching can be effectively prevented. Consequently, a high fluorescence emission can be realized. Second, the highly porous structure of MOFs facilitates rapid analyte diffusion and easy probe–analyte contact within the MOF frameworks, which would inevitably lead to a fast-responsive process. Third, some MOFs, such as the UiO series of MOFs (UiO MOFs, which were first reported by Lillerud et al. in 2008, are three-dimensional porous materials constructed from Zr(IV) and dicarboxylic acid ligands)15 can be readily scaled down to the nanoscale, which makes them suitable for bioimaging. Finally, certain organic sensing groups are not stable under rigorous MOF synthetic conditions such as hydrothermal and solvothermal conditions; however, the post-synthetic modification (PSM) on nanoscale MOFs (NMOFs) will make the decoration of unstable sensing organic functional group on NMOFs feasible.

To date, although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformation.16 In this contribution, we report three new UiO-68 type of MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G′, which were generated via a stepwise PSM process from UiO-68-NH2 in the SCSC manner. The obtained UiO-68-R6G with rhodamine-based moiety can be a highly sensitive and specific chemodosimeter to detect Hg2+ via both visual and fluorogenic observations (turn-on). In addition, nanoscale UiO-68-R6G was prepared and its application for Hg2+ detections in HeLa cells and zebrafish was successfully realized.

Results and discussion

As shown in Scheme 1, bulk UiO-68-NH2 crystals (size: ∼150 μm) were prepared in 35% yield by heating a mixture of H2L-NH2 and ZrCl4 in DMF with benzoic acid at 120 °C for 24 h. After the addition of dry dichloromethane of thiophosgene with triethylamine, the colorless octahedron-shaped UiO-68-NH2 crystals changed to brownish-yellow UiO-68-NCS crystals (95% yield) after reaction for 24 h at room temperature. By further combination with an excess of R6G-EDA in anhydrous dichloromethane in N2 at 40 °C for 24 h and at room temperature for 2 h, the brownish-yellow UiO-68-NCS crystals changed to pale-yellow UiO-68-R6G crystals in 80% yield. When the UiO-68-R6G crystals were soaked in a hot ethanol solution (bath temperature: 80 °C) of Hg(NO3)2 for 2 h, the color of the crystals turned into bright red, and UiO-68-R6G′ crystals were obtained in 65% yield. This visual color change was further confirmed by their UV–vis DRS spectra (ESI). Notably, UiO-68-NCS could not be directly obtained from H2L-NCS with ZrCl4 under the given solvothermal conditions, implying that the -NCS group was not stable under the given synthesis conditions.
image file: c9dt02866h-s1.tif
Scheme 1 Synthesis of UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′ via the PSM approach in the SCSC fashion. Photographs of the corresponding single crystals are inserted. Scale bar: 100 μm.

On the basis of the remarkably stable nature of the MOF crystals, the PSM process could be directly characterized by single-crystal X-ray diffraction. As revealed by the single-crystal analysis, all the four compounds were isostructural and crystallized in the Fm[3 with combining macron]m cubic space group, but with slightly different cell edges (UiO-68-NH2: 32.7135(3) Å; UiO-68-NCS: 32.6875(2) Å; UiO-68-R6G: 32.7408(7) Å; UiO-68-R6G′: 32.635(4) Å), which can be attributed to the different-sized functional groups on MOF linkers (ESI). Unfortunately, the functional groups in the central benzene rings of UiO-68-R6G and UiO-68-R6G′ were statistically disordered and subject to large thermal vibrations and disorders. Therefore, they could not be resolved in the electron map, which was a normal phenomenon encountered in PSM-based SCSC transformations.17 Nonetheless, all the frameworks of the four MOFs unequivocally featured huge 3D percolated pore structures, which facilitated the MOF host to accommodate the large-sized luminophore via PSM in addition to facilitating the fast diffusion of the target analyte within the host framework.

Besides single-crystal analysis, this stepwise PSM process was further verified by the FTIR spectra. As shown in Fig. 1, the weak double peaks at 3441 and 3355 cm−1 belonging to the primary amino group in UiO-68-NH2 disappeared after the formation of UiO-68-NCS. Meanwhile, the sharp peak associated with the -NCS stretching vibration at 2118 cm−1 appeared. After reaction with R6G-EDA, the new weak single peak at 3370 cm−1 and that at 1156 cm−1 clearly indicated the formation of secondary amino and C[double bond, length as m-dash]S groups in UiO-68-R6G, respectively. When it was mixed with Hg2+ in ethanol, the characteristic peaks for the secondary amino and C[double bond, length as m-dash]S groups became significantly weak in UiO-68-R6G′. In addition, we carried out the same functional group transformation on the esterified organic linker of Me2L-NH2, and the stepwise modification progressed very effectively under the given conditions (see the ESI for details). After these successive PSM processes, the measured PXRD patterns of UiO-68-NCS, UiO-68-R6G and UiO-68-R6G′ were found to be identical to those of pristine UiO-68-NH2 (Fig. 1), indicating that their structural integrity and crystallinity were not affected. In addition, this demonstrated that the UiO-68 framework was very stable during the multistep PSM process, which was completely consistent with the results of the single-crystal analysis.


image file: c9dt02866h-f1.tif
Fig. 1 FTIR spectra (left) and measured PXRD patterns (right) of UiO-68-NH2, UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′.

The successful successive rhodamine-thiocarbamide PSM on UiO-68-NH2 was also supported by their dramatic emission change. As shown in Fig. 2, no significant emission changes were observed at the first and second PSM steps, while the third PSM step from UiO-68-R6G to UiO-68-R6G′ caused a dramatic green–yellow emission enhancement at 556 nm (λex = 488 nm), which resulted from a known specific Hg2+-promoted desulfurization reaction within a pH range of 5–10.18 It is well known that desulfurization can cause rhodamine spirolactam ring opening, resulting in the pink coloration and strong fluorescence enhancement of the rhodamine 6G derivative.18 In addition, Hg2+ was present in the form of HgS after this Hg2+-promoted desulfurization reaction, which was effectively supported by the data from the XPS analysis (ESI).


image file: c9dt02866h-f2.tif
Fig. 2 Emission spectra of UiO-68-NH2, UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′ (left) and their N2 adsorption isotherms at 77 K (right).

Accordingly, the large-sized rhodamine-thiocarbamide decoration led to porosity changes. From UiO-68-NH2 to UiO-68-R6G′, the Brunauer–Emmett–Teller (BET) surface areas successively decreased and the corresponding values were found to be 2020, 1712, 619, and 287 m2 g−1 based on their N2 uptake (UiO-68-NH2: 674.46 cm3 g−1; UiO-68-NCS: 620.11 cm3 g−1; UiO-68-R6G: 405.39 cm3 g−1; UiO-68-R6G′: 326.83 cm3 g−1) at 77 K (Fig. 2).

For detecting Hg2+ in bioimaging, nanosized UiO-68-NH2 was prepared under solvothermal conditions (DMF, HOAc, 90 °C, 24 h, 48% yield). Scanning electron microscopy (SEM) measurements revealed that the obtained UiO-68-NH2 NPs were uniform with a diameter less than 200 nm (Fig. 3a), which was further confirmed by dynamic light scattering (DLS) measurements (ESI). The PXRD measurement showed that the nanoscale MOFs featured the same structure as those of the bulk crystals (ESI). Notably, as compared to bulk crystals, the corresponding PSM yields on NMOFs were significantly enhanced (yield: 87–98%) due to the largely enhanced specific surface area. Moreover, the last step in the Hg2+-catalyzed desulfurization process on the UiO-68-R6G NPs was dramatically faster than that on its bulk crystals even under milder conditions. As shown in Fig. 3b (inset, left), when the Hg(NO3)2 solution (10−4 M, 0.1 mL) was added to a suspension of UiO-68-R6G (0.1 mg mL−1) in Tris-HCl (0.9 mL) at 37 °C, the entire response process toward Hg2+ detection was completed within 15 min based on the measured emission intensity. Based on the fluorescence titration experiments, we found that the ratio of Hg2+ to UiO-68-R6G is nearly 1[thin space (1/6-em)]:[thin space (1/6-em)]1 (ESI).


image file: c9dt02866h-f3.tif
Fig. 3 (a) SEM images of UiO-68-NH2, UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′ and their as-synthesized samples. (b) Emission spectra of UiO-68-R6G (0.1 mg mL−1) upon the addition of Hg2+ at different concentrations in the Tris-HCl buffer solution. Ksv = 4.1 × 109 L mol−1. The emission maximum was observed at 566 nm (λex = 488 nm). Linearity relationship between Hg2+ with different concentrations and relative emission intensities, and the time-dependent emission of UiO-68-R6G with the sequential addition of Hg2+ are shown in the insets. (c) Emission response of UiO-68-R6G toward various metal ions (10−4 M) in an aqueous solution (0.9 mL) of UiO-68-R6G (0.1 mg mL−1): (1) blank, (2) Ag+, (3) Ca2+, (4) Co2+, (5) Cr3+, (6) Cu2+, (7) Fe2+, (8) Hg2+, (9) K+, (10) Mg2+, (11) Na+, (12) Ni2+, (13) Pb2+, and (14) Zn2+. The corresponding sample photographs are inserted.

Next, we evaluated the detection limit of UiO-68-R6G for Hg2+ under simulated physiological conditions based on the emission spectra. As shown in Fig. 3b (inset, right), the relative emission intensities toward Hg2+ at different concentrations based on UiO-68-R6G exhibited good linearity in the range of 10−8–10−1 M with a linear coefficient of 0.9960. The limit of detection (LOD) was determined as 0.10 nM based on LOD = 3σ/k (where σ = standard deviation and k = slope of the linear plot)19 (ESI). In contrast, the Hg2+ detection limit of the corresponding organic molecular sensor is ∼10−6 M.18a As compared to the reported MOF-based Hg2+ fluorescence probes, UiO-68-R6G should be one of the most sensitive sensors with the widest detection range for Hg2+ under the simulated physiological conditions (Table S1).

Moreover, UiO-68-R6G showed specific selectivity toward Hg2+ because no specific desulfurization reaction occurred in the presence of other kinds of metal ions, implying that the selectivity of UiO-68-R6G for Hg2+ ions over other various competitive metal ions in the aqueous medium was extremely high (Fig. 3c).

It is suggested that spherical nanoparticles with a size of around 200 nm or less can be readily swallowed by cells via clathrin-mediated endocytosis.20 Considering its excellent fluorescence-based Hg2+ detection feature, we anticipated that UiO-68-R6G with diameter centered at ∼190 nm was certainly suitable for in vitro and in vivo Hg2+ sensing. To this end, HeLa cells were selected and used as a model for exogenous Hg2+ detection for the first time in living cells.

After incubating with 25 μM UiO-68-R6G in Tris-HCl for 30 min, the HeLa cells were washed several times with DPBS. As shown in Fig. 4a–c, no significant fluorescence was observed in the cells after incubating with only UiO-68-R6G by confocal laser scanning microscopy (λex = 488 nm, within 540–580 nm). In contrast, after successively incubating with Hg(NO3)2 (5 μM, 30 min) and UiO-68-R6G (25 μg mL−1, 30 min) at 37 °C, the HeLa cells exhibited very strong intracellular fluorescence in the red channel (Fig. 4d–f), indicating that UiO-68-R6G can respond to intracellular Hg2+ under physiological conditions. In addition, the good morphology of HeLa cells after incubation with UiO-68-R6G implied that this MOF probe possessed good biocompatibility (Fig. 4c and f). In addition, an MTT assay on HeLa cells with 2–50 μg mL−1 was performed (ESI), implying that the MOF probe possessed low cytotoxicity. Therefore, UiO-68-R6G is a useful MOF-based fluorescent probe for in vitro Hg2+ detection.


image file: c9dt02866h-f4.tif
Fig. 4 Confocal fluorescence images in living cells: (a) image of HeLa cells incubated with 25 μg mL−1 UiO-68-R6G; (b) dark-field image of (a); (c) overlay of (a) and (b); (d) image of HeLa cells preincubated with 5 μM Hg2+ and then incubated with 25 μg mL−1 UiO-68-R6G; (e) dark-field image of (d); (f) overlay of (d) and (e). Scale bar: 20 μm.

Besides in vitro experiments, in vivo experiments were also performed to examine if the NMOF sensor of UiO-68-R6G could be used to image Hg2+ in living organisms. For this, a 3-day-old zebrafish was exposed to the UiO-68-R6G probe in the presence and absence of Hg2+. Once the zebrafish was treated with 50 μM of Hg2+ in the E3 embryo media at 28 °C for 1 h and washed with PBS to remove the remaining Hg2+, the zebrafish was then incubated with nanosized UiO-68-R6G (10 μg mL−1) in a solution for 4 h. As shown in Fig. 5a–c, the NMOF probe loaded with the 3-day-old zebrafish displayed strong fluorescence (λex = 488 nm; fluorescent signals were collected at 540–580 nm), indicating that UiO-68-R6G was tissue-permeable and Hg2+ was readily uploaded by the zebrafish and accumulated in its body at a detectable Hg2+ level. Notably, the fluorescence in the zebrafish was not uniformly distributed, and the zebrafish yolk sac exhibited very weak fluorescence under the given conditions. In contrast, the 3-day-old zebrafish exhibited almost no background fluorescence without Hg2+ treatment under the same conditions (Fig. 5d–f). The zebrafish remained alive throughout the imaging experiments. This preliminary in vivo study demonstrated that the NMOF probe with UiO-68-R6G has potential applications in detecting Hg2+ accumulation in living organisms.


image file: c9dt02866h-f5.tif
Fig. 5 Bright-field (a, d), dark-field (b, e), and overlaid (c, f) images of a 3-day-old zebrafish treated with nanosized UiO-68-R6G (10 μg mL−1) in the presence (a, b, and c) and absence (d, e, and f) of Hg2+ (50 μM).

Conclusions

In summary, we reported three new MOFs, namely, UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G′, from UiO-68-NH2 via stepwise PSM in the SCSC manner, where the fluorescent molecular rhodamine 6G was successfully grafted onto MOFs through covalent bonding interactions without destroying the UiO-68 structure. In addition, the nanoscale UiO-68-R6G exhibited excellent photophysical properties for biological applications via an irreversible desulfurization reaction, and it could be a highly sensitive and selective NMOF-based fluorescent probe to detect Hg2+ in living cells and living organisms. We expect that this approach will be viable for the construction of new, additional, and practical fluorescent NMOF probes of such types, and studies toward the preparation of new MOF-based fluorescent sensing systems for detecting other kinds of analytes are underway.

Experimental section

Synthesis of UiO-68-NH2 bulk crystals and its PSM

ZrCl4 (9.6 mg, 0.041 mmol), H2L-NH2 (23.3 mg, 0.070 mmol), and benzoic acid (222.6 mg, 1.82 mmol) were dissolved in DMF (3 mL) and then filtered into a Pyrex glass tube. The tightly capped flasks were kept in an oven at 120 °C under static conditions. After 24 h, the reaction system was cooled to room temperature and the bulk colorless crystals at 5.5 mg were obtained in 35% yield. The crystals were suspended in fresh DMF (10 mL) overnight. After soaking in methylene chloride for 3 days, the crystals were centrifuged and dried. FTIR (KBr pellet cm−1): 3441 (m), 3355 (m), 2948 (m), 1712 (s), 1605 (s), 1551 (m), 1433 (m), 1395 (m), 1284 (s), 1180 (m), 1104 (m), 767 (s), 704 (s), 512 (w). Elemental analysis (%) calcd for the desolvated sample C120H82N6O32Zr6: C 54.04, H 3.10, N 3.15; found: C 53.78, H 3.24, N 3.33.

The bulk crystals of UiO-68-NH2 (443 mg, 1.0 mmol), thiophosgene (120 μL, 1.5 mmol), and triethylamine (0.1 mL, 0.7 mmol) were combined in fresh distilled methylene chloride (10 mL) and the mixed solution was stayed for 24 h at room temperature. In the end, the reaction mixture was replaced with methylene chloride three times. The product was sealed in the reaction bottle with fresh methylene chloride. The color of the colorless crystals changed to brownish yellow to generate UiO-68-NCS. The yield was calculated based on the N[thin space (1/6-em)]:[thin space (1/6-em)]S ratio by elemental analysis, indicating ∼95% of the organic ligand in UiO-68-NH2 was functionalized with -NCS. Elemental analysis (%): C 48.86, H 2.55, N 2.81, S 6.10. Empirical formula: C125.7H66.6N6O32S5.7Zr6. FTIR (KBr pellet cm−1): 2953 (m), 2289 (m), 2118 (s), 1709 (w), 1606 (m), 1431 (m), 1276 (s), 1183 (m), 1108 (s), 828 (w), 769 (m), 703 (m).

The bulk crystals of UiO-68-NCS and N-(rhodamine-6G)lactam-ethylenediamine (R6G-EDA) (684 mg, 1.5 mmol) were combined in fresh distilled methylene chloride (10 mL). The reaction solution was maintained at 40 °C for 24 h under a N2 atmosphere and stayed for an additional 2 h at room temperature. The reaction mixture was replaced with methylene chloride three times and finally replaced with ethanol. The color of the crystals changed to pale yellow to generate UiO-68-R6G. The yield was calculated based on the N[thin space (1/6-em)]:[thin space (1/6-em)]S ratio by elemental analysis, indicating that ∼80% of organic ligand in UiO-68-NCS was functionalized with -R6G. Elemental analysis (%) found: C 57.84, H 4.01, N 6.79, S 3.65. Empirical formula: C260.3H222.9N25.2O30.4S5.9Zr6. FTIR (KBr pellet cm−1): 3350 (m), 2113 (w), 1600 (s), 1531 (s), 1417 (s), 1216 (w), 1156 (w), 1016 (w), 778 (m), 654 (m), 514 (w).

The bulk crystals of UiO-68-R6G (200 mg, 0.2 mmol) and Hg(NO3)2 hydrate (400 mg, 1 mmol) were combined in 100 mL hot ethanol (bath temperature: 80 °C). The reaction mixture was stayed for 2 h. The solvent was removed and washed with ethanol three times and replaced with methylene chloride. The color of the crystals changed to bright red to yield UiO-68-R6G′. The yield was calculated based on the Zr[thin space (1/6-em)]:[thin space (1/6-em)]Hg ratio (1[thin space (1/6-em)]:[thin space (1/6-em)]0.50) by ICP-OES analysis, indicating that the Hg2+-catalyzed desulfurization yield was ∼65%. Elemental analysis (%): C 50.67, H 3.54, N 6.27, S 3.04. Empirical formula: C282.2H240.5N28.3O39.2S2.0Zr6. FTIR (KBr pellet cm−1): 3381 (w), 1604 (s), 1532 (s), 1418 (s), 1303 (w), 1016 (w), 777 (m), 658 (m).

Synthesis of UiO-68-NH2 nanosized crystals and its PSM

H2L-NH2 (9.6 mg, 0.041 mmol) and ZrCl4 (13.6 mg, 0.041 mmol) were dissolved into DMF (3.2 mL). Then, HOAc (120 μL) and H2O (40 μL) were respectively added into the above solution. The reaction mixture was kept in an oven at 90 °C under static conditions. After 24 h, the reaction system was cooled to room temperature. The suspension was collected by centrifugation at 13[thin space (1/6-em)]000 rpm and respectively washed with DMF and ethanol. The solids were dried in a vacuum at 60 °C for 24 h; yield: 48% (75 mg). IR (KBr pellet cm−1): 3335 (m), 3307 (m), 2973 (s), 1595 (s), 1537 (s), 1413 (s), 1204 (m), 1087 (w), 1045 (s), 876 (m), 780 (m), 656 (m). Elemental analysis (%): calcd for the desolvated sample C120H82N6O32Zr6: C 54.04, H 3.10, N 3.15; found: C 53.89, H 3.21, N 3.28.

Nanosized UiO-68-NH2 (443 mg, 1.0 mmol) and triethylamine (0.1 mL, 0.7 mmol) were combined in fresh distilled methylene chloride (10 mL). A mixture solution of thiophosgene (120 μL, 1.5 mmol) and methylene chloride (5 mL) was added dropwise. The reaction solution was stirred for 2 h at room temperature. The suspension was collected by centrifugation and washed with methylene chloride three times. The solid was dried in a vacuum at 80 °C for 5 h to yield the activated sample. The yield was calculated based on the N[thin space (1/6-em)]:[thin space (1/6-em)]S ratio by elemental analysis, indicating that ∼98% of the organic ligand in UiO-68-NH2 was functionalized with -NCS. Elemental analysis (%): C 49.67, H 2.47, N 2.87, S 6.43. Empirical formula: C125.9H70.2N6O32S6Zr6. FTIR (KBr pellet cm−1): 3364 (m), 2161 (w), 2112 (s), 1587 (m), 1539 (m), 1417 (s), 1184 (w), 1104 (w), 1016 (w), 777 (m), 652 (m).

Nanosized UiO-68-NCS (486 mg, 1.0 mmol) and R6G-EDA (684 mg, 1.5 mmol) were combined in fresh distilled methylene chloride (10 mL). The reaction solution was refluxed for 24 h under a N2 atmosphere and stirred for additional 2 h at room temperature. The suspension was collected by centrifugation and washed with ethanol three times. The solid was dried in a vacuum at 80 °C for 5 h to afford light-yellow solids. The yield was calculated based on the N[thin space (1/6-em)]:[thin space (1/6-em)]S ratio by elemental analysis, indicating that ∼90% of the organic ligand in UiO-68-NCS was functionalized with -R6G. Elemental analysis (%): C 61.92, H 4.67, N 7.36, S 3.66. Empirical formula: C277.2H242.8N27.6O42.8S6Zr6. FTIR (KBr pellet cm−1): 3365 (m), 2111 (w), 1693 (s), 1531 (s), 1416 (s), 1270 (w), 1216 (w), 1156 (w), 1016 (w), 778 (m), 653 (m), 514 (w).

Nanosized UiO-68-R6G (2 mg, 0.002 mmol) and Hg(NO3)2 hydrate (4 mg, 0.01 mmol) were combined in 2 mL of water. The mixture was allowed to stay at 37 °C in the water bath for 15 min. The suspension was collected by centrifugation and washed with ethanol (three times). The solids were dried in a vacuum at 80 °C for 5 h, yielding bright-red solids of UiO-68-R6G′. The yield was calculated based on the Zr[thin space (1/6-em)]:[thin space (1/6-em)]Hg ratio (1[thin space (1/6-em)]:[thin space (1/6-em)]0.77) by ICP-OES analysis, indicating that the Hg2+-catalyzed desulfurization yield was ∼87%. Elemental analysis (%): C 48.13, H 3.42, N 5.57, S 2.75. Empirical formula: C291.8H249.1N29.7O43.8S0.8Zr6. FTIR (KBr pellet cm−1): 3354 (w), 1593 (s), 1531 (s), 1416 (s), 1303 (w), 1186 (w), 1016 (w), 1010 (w), 779 (m), 657 (m).

Cell culture and treatments

The HeLa cell line was provided by the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). The HeLa cell line was cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 U mL−1 penicillin, and 100 μg mL−1 streptomycin in an atmosphere of 5% CO2 and 95% air at 37 °C. For confocal fluorescence imaging, the cells were incubated in glass bottom dishes for 24 h. The cells were incubated at 37 °C with Hg(NO3)2 (5 μM) for 0.5 h, washed with Dulbecco's phosphate-buffered saline (DPBS), incubated at 37 °C with NMOF (25 μg mL−1) for 0.5 h, and washed with DPBS; then, the fluorescence images were captured. The cells without Hg(NO3)2 were used as the control. The samples were excited at 488 nm and observed between 540 and 580 nm.

Fluorescent detection of Hg2+ in zebrafishes

All the animal experiments were carried out according to the Principles of Laboratory Animal Care (People's Republic of China) and the Guidelines of the Animal Investigation Committee, Biology Institute of Shandong Academy of Science, China. The zebrafishes were kept at 28 °C and maintained under optimal breeding conditions. For mating, male and female zebrafishes were maintained in one tank at 28 °C on a 12 h light/12 h dark cycle and then the spawning of eggs was triggered by giving light stimulation in the morning. Almost all the eggs were immediately fertilized. All the stages of zebrafishes were maintained in an E3 embryo media (15 mM NaCl, 0.5 mM KCl, 1 mM MgSO4, 1 mM CaCl2, 0.15 mM KH2PO4, 0.05 mM Na2HPO4, 0.7 mM NaHCO3, 5–10% methylene blue; pH 7.5). For the imaging experiment, 3-day-old zebrafishes were incubated with 10 M BAN solution for 20 min at room temperature. The solution was then removed, and the zebrafishes were washed with PBS (2 mL × 3) to clear the BAN molecules attached to the surface of zebrafishes. Subsequently, the zebrafishes were incubated for 1 h with 50 μM Hg(NO3)2 solution at room temperature. After the removal of the culture medium, the treated zebrafishes were rinsed three times with PBS (2 mL × 3). Then, the zebrafishes were incubated for 4 h with 10 μg mL−1 NMOF solution at room temperature. After the removal of the culture medium, the treated zebrafishes were rinsed three times with PBS (2 mL × 3) before observation. The zebrafishes without Hg(NO3)2 were used as the control. The fluorescent images of the treated zebrafishes were captured by confocal laser scanning microscopy (λex = 488 nm; fluorescent signals were collected at 540–580 nm).

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We are grateful for financial support from NSFC (Grant No. 21971153, 21671122, 21475078 and 21805172), the Taishan Scholar's Construction Project, the Doctoral Fund of Shandong Province (Grant No. ZR2017BB067), and China Postdoctoral Science Foundation funded project (Grant No. 2017M612328).

Notes and references

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Footnotes

Electronic supplementary information (ESI) available: Materials and instrumentation, synthesis and additional characterization of H2L-NH2, UV-vis DRS spectra, DLS, PXRD of the nanosized UiO-68-NH2, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G′, single-crystal data. CCDC 1847052, 1847053, 1856366 and 1856367. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9dt02866h
These authors contributed equally to this work.

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