A Ni(II)MOF-based hypersensitive dual-function luminescent sensor towards the 3-nitrotyrosine biomarker and 6-propyl-2-thiouracil antithyroid drug in urine

Abstract

Trace detection of bioactive small molecules (BSMs) in body fluids is of great importance for disease diagnosis, drug discovery, and health monitoring. Based on the chiral ligand of 4,4′-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid (H₂L), an achiral 3D porous Ni(II)-MOF, with a trinuclear cluster based (3,9)-c {4²·6}₃{4⁶·6²¹·8⁹}-xmz net, was constructed under solvothermal conditions. Benefiting from its robust framework and excellent luminescent performance, NiMOF was endowed with remarkable capabilities in efficiently, rapidly, and sensitively detecting the 3-nitrotyrosine (3-NT) biomarker and 6-propyl-2-thiouracil (6-PTU) thyroid drug based on the spectral overlap and photo-induced electron transfer (PET) caused luminescence quenching response. Notably, NiMOF exhibited exceptional performance in quantifying 3-NT and 6-PTU in urine samples, yielding highly satisfactory results. Additionally, an intelligent detection system was crafted to enhance the reliability and practicability of 3-NT/6-PTU detection in urine, based on tandem combinational logic gates. This work not only heralds a promising trajectory in the development of MOF-based luminescent sensors, but also paves the way for the intelligent monitoring of BSMs in real bodily fluids.

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Introduction

Bioactive small molecules (BSMs), belonging to a class of biologically potent compounds, possess remarkable ability to traverse cell membranes, enabling them to enter cells and engage with proteins through specific target sites.¹ This interaction facilitates the execution of vital biological functions, thereby occupying a pivotal position in numerous life science domains, including disease diagnosis, drug discovery, and health monitoring.² In terms of the source of BSMs, they can be categorized as endogenous BSMs (e.g., disease markers, hormones, and metabolites) and exogenous BSMs (drugs, ingested toxic substances, etc.). Here, 3-nitrotyrosine (3-NT), which is the final product of tyrosine nitration and a biomarker of oxidative stress, was selected as an endogenous BSM as its serum level is closely related to Alzheimer's disease, myocarditis, asthma and meningitis.^3,4 Normal 3-NT levels in healthy individuals range from 0.64 to 2.8 nM, whereas patients with renal failure have significantly elevated levels of 3-NT, even reaching a concentration range of 10 to 60 μM.⁵ Meanwhile, a typical antithyroid drug, 6-propyl-2-thiouracil (6-PTU), which was designed 70 years ago, was selected as a representative exogenous BSM due to its serious side effects that damage the liver and kidneys.⁶ In view of the physiological importance of 3-NT biomarkers and 6-PTU drugs, it is particularly important to realize their rapid detection and daily monitoring in body fluids. Currently, there are many quantitative detection methods for 3-NT and 6-PTU, such as enzyme-linked immunoassay, liquid chromatography, and surface-enhanced Raman scattering (SERS), etc. However, these techniques are generally characterized by the limitations of cumbersome operation, high instrumentation cost, and the need for professional skills in sample pre-treatment, which have greatly limited their wide application.^7,8 Compared with the aforementioned traditional techniques, luminescent sensors present obvious superiorities in operability, reliability, scalability, and cost performance.

Metal–organic frameworks (MOFs) represent a class of highly ordered porous crystalline materials that are constructed from organic ligands and metal centres through a periodic arrangement, and have attracted attention because of the great potential they exhibit in a variety of fields such as adsorption, separation, catalysis, and drug delivery.^9–23 Through targeted selection of the desired organic ligands and metal centers, MOFs are endowed with great potential as luminescent sensors in the sensing of anions and cations, volatile organic compounds, and emerging pollutants in water.^24–29 However, few reports on MOF-based sensors have focused on the detection of BSMs in bodily fluids, due to the complex detection environments.^30–32 It is universally acknowledged that the performance of MOFs is inherently dictated by their intricate structures, which are subsequently shaped and influenced by the building blocks. Considering the important role of chirality in life activities and the chemical structures of two targeted BSMs (Scheme 1), chiral ligands rich in hydroxyl groups seem a promising approach to engineer ideal luminescent MOFs.³³ The hydroxyl groups can be strategically introduced into the confined spaces of designed MOFs as active sites through a ligand pre-design strategy to guarantee the sensing specificity. Meanwhile, the microenvironment of confined spaces empowered by chiral ligands can ensure the sensing selectivity through confined space effects.

Scheme 1 Chemical structures of target BSMs and the H₂L ligand.

Inspired by the above viewpoints and as a continuation of our research interest of BSM trace detection in bodily fluids,^34,35 here a chiral ligand of 4,4′-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid (H₂L), which is rich in hydroxyl groups, was introduced to construct MOFs through coordination interactions. Fortunately, a stable NiMOF, {[Ni₃(L)₃(μ₂-H₂O)]·6H₂O·2DMA}_n, with a trinuclear cluster based (3,9)-connected {4²·6}₃{4⁶·6²¹·8⁹}-xmz net, was constructed. Further luminescent sensing investigations illustrated that the prepared NiMOF not only exhibited efficient and specific detectability toward the 3-NT biomarker, but also achieved high sensitivity and rapid detection of antithyroid drug 6-PTU in urine for the first time, expanding the application of MOF-based luminescent sensors in the field of life and health sciences (Scheme 2). In addition, the luminescence quenching response mechanisms have been explored from spectral overlap and theoretical calculations.

Scheme 2 Schematic diagram of the NiMOF-based luminescent sensor towards the 3-NT biomarker and 6-PTU antithyroid drug.

Results and discussion

Structural description of the NiMOF

Although the H₂L ligand is chiral, structural analysis revealed that the NiMOF crystallizes within the monoclinic crystal system, with achiral C₂/c space group.³⁶ Specifically, the asymmetric unit of NiMOF comprises one and a half Ni^II cations, one and a half L²⁻ ligands, and a single μ₂-coordinated water molecule. As depicted in Fig. 1, Ni1 exhibits a distorted {NiO₆} octahedral coordination geometry, encircled by three carboxyl O atoms (O7, O8, and O4ⁱ) stemming from two distinct L²⁻ ligands, two hydroxyl O atoms (O5 and O6) from another L²⁻ ligand, and half a μ₂-coordinated water molecule (O1W). Conversely, Ni2 resides at the centre of a C₂-axisymmetric {NiO₆} octahedral coordination geometry, completed by carboxyl O atoms (O2 and O2ⁱⁱ), two hydroxyl O atoms (O9ⁱⁱⁱ and O9^iv), and two halves of μ₂-coordinated water molecules (O1W^iv and O1W^v). Furthermore, the Ni–O bond lengths vary within the range of 2.067(2) Å to 2.188(7) Å.

Fig. 1 The asymmetric unit of NiMOF (symmetry codes: (i) 0.5 − x, −0.5 + y, 1.5 − z; (ii) −x, y, 0.5 − z; (iii) x, 1 + y, z; (iv) −x, 1 + y, 0.5 − z; (v) −x, 1 − y, 1 − z; (vi) x, 1 − y, −0.5 + z).

In the formation of NiMOF, the chiral H₂L is completely deprotonated and adopted two different coordination modes of (κ¹–κ⁰)-(κ¹–κ¹)-(κ¹–κ⁰)-μ₃ (Mode I) and (κ¹–κ¹)-(κ¹–κ¹)-(κ¹–κ¹)-μ₃ (Mode II), with the dihedral angles of 53.08° and 76.55° between two phenyl rings (Fig. S1, ESI†). It is worth noting that the ortho-dihydroxy groups in both kinds of L²⁻ ligands display trans-configurations to chelate with Ni^II cations, which were further bridged by the μ₂ coordinated water to form a trinuclear cluster, with the Ni1⋯Ni2 distance being 3.921(6) Å (Fig. S2, ESI†). Each trinuclear cluster linked with six Mode I type L²⁻ ligands and three Mode II type L²⁻ ligands to leave a 3D porous framework with sugarcoated haws shaped channels (Fig. 2a and Fig. S3, ESI†). The segment space presents a nanocaged structure, with the diameter size being 8.4 Å (Fig. 2b). And the calculated porosity can reach 42.9% (2940.2 ų out of 6851.2 ų for per unit cell) after removing all free solvents.³⁷

Fig. 2 Nanocages (a) and 3D porous framework (b) of the NiMOF. (c) A trinuclear cluster-based 3,9-c {4²·6}₃{4⁶·6²¹·8⁹}-xmz net of NiMOF.

To better understand the arrangement of L²⁻ ligands and trinuclear clusters in the NiMOF, topology analysis indicated that the 3D architecture of the NiMOF can be simplified into a 3,9-c {4²·6}₃{4⁶·6²¹·8⁹}-xmz net,³⁸ by denoting two kinds of μ₃-L²⁻ ligands and trinuclear clusters as 3-connected and 9-connected nodes, respectively (Fig. 2c and Fig. S4, ESI†).

Stability characterization of the NiMOF

Considering the actual presence of the antithyroid drug 6-PTU and 3-NT biomarker is mainly in urine, the chemical stability of NiMOF is indispensable. Considering the pH of human urine typically varies between 4.6 and 8.0, the chemical stability of NiMOF in 100-fold diluted urine and aqueous solutions of different pH values (pH values ranging from 4 to 8) was determined. After soaking in the above solutions for 12 hours, the PXRD patterns of NiMOF were tested and remained consistent with the original ones, demonstrating the excellent chemical stability of the NiMOF (Fig. S5 and S6, ESI†), which was also proved by the FT-IR (Fig. S7, ESI†) and luminescence (Fig. S8, ESI†) results. The above evaluation intuitively presents the excellent practicality of the prepared NiMOF in practical testing. Furthermore, the thermal stability of the NiMOF was evaluated through thermogravimetric analysis. As depicted in Fig. S9 (ESI†), the initial weight loss of 7.67% observed before 148 °C is primarily attributed to the evaporation of lattice water molecules (calc. 7.74%). Subsequently, in the temperature range of 148–270 °C, the second weight loss of 12.23% was mainly due to the release of DMA molecules (calc. 12.48%). Then, the framework remained robust and stable until the temperature increased up to 400 °C. Upon exceeding this critical temperature threshold, the framework began to collapse and eventually cracked into a gray powder, with the quality percentage being 18.04%. Taking into consideration that the pyrolysis was carried out under a nitrogen atmosphere, the final residue was considered to be a mixture of NiO (16.06%) and residual carbon material.

Solid state luminescence and luminescent sensing performance of NiMOF

On the basis of ensuring the long-term stability of the NiMOF in the detection environment, its inherent luminescence performance was thoroughly investigated. When excited at 336 nm, the NiMOF displayed a strong emission peak at 448 nm, redshifted from the emission peak at 427 nm for H₂L (Fig. S10, ESI†), which can be mainly attributed to the charge transfer within the framework.^39,40 In order to accurately evaluate the real levels of anti-thyroid drug 6-PTU and 3-NT biomarker in the human body, the residual concentrations present in urine serve as an outstanding monitoring resource, owing to its non-intrusive nature and the absence of burdensome post-processing requirements. Hence, the possible urine species of NaCl, KCl, MgCl₂, CaCl₂, NH₄Cl, urea, UA, Crea, Cre, Gluc, His, Phe, and Cys were selected. By testing the emission spectra of NiMOF suspensions (1 mg/2 mL), which contained 10 mM of the above-mentioned urine species, 6-PTU anti-thyroid drug and 3-NT biomarker, the results indicated that both monitoring analytes of 3-NT and 6-PTU exhibited remarkable luminescence quenching responses, while other interfering urine species did not change significantly (Fig. 3 and Fig. S11, ESI†). It should be pointed out that although both target analytes exhibited significant luminescence quenching effects to NiMOF, it does not affect the sensing selectivity in actual detection for two target analytes corresponding to different diseases that almost never occur simultaneously.

Fig. 3 Luminescence intensity of NiMOF suspensions containing 10 mM urine species.

Detectability and practicability of NiMOF towards the 3-NT biomarker

3-Nitrotyrosine (3-NT) is a typical biomarker that reflects the specific level of cellular oxidative damage. It is essential to detect the real 3-NT levels for the early diagnosis of related diseases. To better evaluate the detectability and practical performance of the NiMOF as a luminescence sensor in 3-NT detection, series luminescence gradient titration, anti-interference, response time, and recyclability were comprehensively studied. With the continuous addition of 3-NT biomarker into NiMOF aqueous suspensions and thoroughly mixing to test the emission spectra, it was evident that the luminescence intensity at 448 nm gradually decreased (Fig. 4a and Fig. S12, ESI†), with the CIE ranging from (0.14, 0.09) to (0.15, 0.14) (Fig. 4b). It is worth noting that there is an exponential functional relationship between concentration and relative intensity of I₀/I: I₀/I = 1.06e^18911[3-NT] − 0.14 in the concentration range of 0–0.10 mM (Fig. 4c), with the quenching constant K_sv being 3.11 × 10⁴ M⁻¹.⁴¹ According to the LOD = 3σ/K_sv (here σ is the standard deviation of 10 cycles of blank samples), the detection limit was calculated to be 0.31 μM (0.07 μg mL⁻¹), comparable or even superior to most reported MOF-based 3-NT luminescent sensors,^35,42–46 which illustrated the high sensitivity of the prepared NiMOF in 3-NT detection (Table S1, ESI†). In confirmation of the rapid detection performance of NiMOF in sensing the 3-NT biomarker, the dynamic response time was conducted and proved to be as low as 40 seconds (Fig. S13, ESI†). By adding an equal amount of interfering species into the NiMOF suspensions containing 3-NT, the potential interference of other urine species on the overall sensing results was also investigated. The results in Fig. S14 (ESI†) clearly show that the interfering substances in urine did not interfere with the specific detection of 3-NT. Furthermore, to validate the cyclic nature of the sensing procedure, the aforementioned sensing process was reiterated, employing recycled samples that underwent filtration, washing, and subsequent drying. The results of the cyclicity of the sensing experiments showed that the quenching efficiency remained well for at least 5 cycles (Fig. 4d). And the comparable PXRD patterns in Fig. S15 (ESI†) as well as the FT-IR spectra in Fig. S16 (ESI†) of the recycled samples after 5 cycles of sensing were also conducted, which further illustrated the good recyclability of the NiMOF.

Fig. 4 (a) Emission spectra of NiMOF aqueous suspensions with different amounts of 3-NT. (b) The trend of the CIE chromaticity diagram of NiMOF controlled by 3-NT concentration. (c) Relationship between 3-NT concentration and I₀/I of NiMOF. (d) Recycling performance of NiMOF in sensing 3-NT.

Although the main species in urine do not have a significant impact on 3-NT sensing, it must be acknowledged that there are some differences in the sensing process between real samples and aqueous solutions. Hence, the detection performance in real samples was investigated by replacing the aqueous environment with 100-fold diluted urine. Series luminescence quenching gradient titration was conducted in the 3-NT concentration range of 0–0.1 mM (Fig. 5a), and the Stern–Volmer equation of I₀/I = 26740[3-NT] + 0.8873 (K_sv = 2.67 × 10⁴ M⁻¹, R² = 0.9584) was calculated in the low concentration range (Fig. 5b). The results indicated that NiMOF seems to display better sensing performance, which can be attributed to the main components (NaCl, KCl, NH₄Cl, Urea, and UA) in urine having a slight effect on the luminescence intensity of NiMOF, finally leaving the synergistic recognition effects in the 3-NT sensing process. On this basis, the detection performance of NiMOF in real urine samples was evaluated by the spiked internal standard method. The results indicated that the recovery rate range of 98.5–103.8% and the RSD of 2.23–3.72% are satisfactory (Table 1). All experimental results clearly demonstrate the efficacy of the NiMOF in quantitatively detecting 3-NT in urine samples.

Fig. 5 (a) 3-NT controlled series luminescence quenching gradient titration in diluted urine. (b) Stern–Volmer equation between the 3-NT concentration and relative intensity of NiMOF in diluted urine.

Table 1 Results of NiMOF as a luminescent sensor for the quantitative detection of 3-NT in diluted urine samples

Added (μM)	Found (μM)	RSD (%)	Recovery (%)
10	10.06	2.67	100.6
20	20.75	3.72	103.8
30	30.82	3.68	102.7
40	39.91	2.23	99.8
50	49.23	2.89	98.5

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Detectability and practicability of the NiMOF towards 6-PTU antithyroid drug

In addition to focusing on endogenous biomarkers, the detection of exogenous drug molecules in urine is equally crucial. This is because chronic disease patients taking drugs for a long period of time may lead to excessive accumulation of drug molecules in the body, which in turn may cause irreversible damage to liver and kidney functions. In order to achieve effective treatment and minimize side effects, it is particularly important to monitor the actual levels of drug molecules in urine on a regular basis and to adjust the drug dosage in a timely manner according to the monitoring results. This work investigates 6-propyl-2-thiouracil (6-PTU), a representative antithyroid medication, as the exogenous drug molecule under scrutiny. As shown in Fig. 5, the sensing results clearly demonstrate that 6-PTU produces a significant luminescence quenching response to NiMOF, and its response time is extremely rapid, not exceeding 40 seconds (Fig. S17, ESI†). Further anti-interference performance indicated that the selectivity of NiMOF in detecting 6-PTU can be guaranteed in the presence of other interfering analytes (Fig. S18, ESI†). Then, gradient titration tests were conducted and the monitoring signal at 448 nm showed a very significant decrease (Fig. 6a and Fig. S19, ESI†), with the CIE coordinates ranging from (0.15, 0.08) to (0.16, 0.09) (Fig. 6b). Following the Stern–Volmer equation above, the corresponding equation is obtained: I₀/I = 16870[6-PTU] + 0.9934 (K_sv = 1.68 × 10⁴ M⁻¹, R² = 0.9956) in the low concentration range (Fig. 6c), with the calculated LOD being 0.57 μM (0.10 μg mL⁻¹). To the best of our knowledge, this is the first sample where MOFs were used as luminescent sensors to detect 6-PTU antithyroid drug. Reusability tests show that NiMOF can be reused up to five times in detecting 6-PTU, and the sensing capability is still impressive (Fig. 6d). Similarly, the recyclability and stability of NiMOF were also proved by undergoing PXRD and FT-IR testing (Fig. S15 and S16, ESI†).

Fig. 6 (a) Emission spectra of NiMOF aqueous suspensions upon gradual addition of 6-PTU. (b) CIE chromaticity diagram trend of NiMOF, controlled by 6-PTU concentration. (c) The relationship between 6-PTU concentration and relative intensity of I₀/I of NiMOF. (d) The recycling performance of NiMOF in the detection of 6-PTU.

The superior selectivity, low detection limit, quick response time, and high reliability of the NiMOF in sensing 6-PTU inspired us to delve deeper into the presence of 6-PTU in real urine samples. Therefore, the luminescent sensing gradient titration was carried out in urine samples. A set of 6-PTU concentration controlled emission spectra were collected in Fig. 7a and a favourable linear relationship of I₀/I = 15482[6-PTU] + 0.8996 (K_sv= 1.54 × 10⁴ M⁻¹, R² = 0.9932) in the low concentration range (0–50 μM) was found (Fig. 7b). Tests in real samples were carried out by the spiked internal standard method, and the results were calculated according to the above linear equation. The results implied that the recoveries were in the range of 98.4–104.3%, and the RSD was less than 3.16% (Table 2), demonstrating that NiMOF can be employed to quantify the antithyroid drug 6-PTU in real urine samples with high applicability and reliability.

Fig. 7 (a) 6-PTU controlled series luminescence quenching gradient titration in diluted urine. (b) Stern–Volmer equation between the 6-PTU concentration and relative intensity of NiMOF in diluted urine.

Table 2 Results of NiMOF as a luminescent sensor for the quantitative detection of 6-PTU in diluted urine samples

Added (μM)	Found (μM)	RSD (%)	Recovery (%)
5	5.17	2.91	103.4
10	9.84	3.16	98.4
15	15.65	2.98	104.3
20	20.22	1.93	101.1
25	24.69	2.77	98.8

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Possible sensing mechanism

The development of MOFs with efficient specificity for the detection of BSMs is of great value, and an in-depth investigation of their mechanism of action is essential to guide the design of future MOF-based luminescent sensors. Therefore, an in-depth exploration was undertaken to elucidate the potential mechanism of interaction between NiMOF and 3-NT, as well as 6-PTU. Initially, the structural integrity of NiMOF was validated by contrasting its pristine form with its state post-sensing of 3-NT and 6-PTU. This verification precludes the possibility of luminescence enhancement stemming from structural degradation, thereby ensuring the stability of the material (Fig. S15, ESI†). For light-responsive sensors, spectral overlap is a factor that must be emphasized. As depicted in Fig. 8, there is a pronounced overlap discernible between the absorption bands of 3-NT and the excitation/emission spectra of NiMOF, suggesting the likelihood of Förster resonance energy transfer (FRET) occurring alongside an internal filtering effect (IFE).^47,48

Fig. 8 Spectral overlaps of the emission (a) or excitation (b) spectra of NiMOF and the UV-Vis absorption spectra of urine species.

In terms of luminescence quenching response, it is highly probable that photo-induced electron transfer (PET) plays a significant role due to the electron-rich frameworks of MOFs.^49,50 Based on density-functional theory, the LUMO and HOMO energy levels of H₂L, 3-NT, and 6-PTU were precisely calculated with the help of Gaussian 09 software by employing the B3LYP-6-31g* basis set. As depicted in Fig. 9, the LUMO of H₂L stands notably higher than that of 3-NT and 6-PTU, illustrating that excited electrons in H₂L predominantly migrate from its LUMO directly to the LUMO of the analytes, bypassing its own HOMO, ultimately leading to luminescence quenching. Therefore, electron transfer from NiMOF to 3-NT and 6-PTU is theoretically feasible, which confirms the presence of PET. Drawing from the aforementioned analysis, the luminescence quenching mechanisms for sensing 3-NT entailed a synergistic interplay between FRET, IFE, and PET. In the case of 6-PUT sensing, the PET mechanism played a pivotal role.

Fig. 9 Refined and optimized LUMO and HOMO levels of 3-NT, 6-PTU and H₂L.

Logic gate operation

To further enhance the convenience and intelligence of NiMOF as the luminescent sensor in detecting the 3-NT biomarker and antithyroid drug 6-PTU in urine, tandem combinational logic gate-based intelligent detection platforms were designed based on the relative luminescence intensity values. For the two target BSM analytes, the intelligent detection systems are similar, only with differences in the analyte concentrations and thresholds. Therefore, the intelligent system for 6-PTU detection was described in detail below as a representative. Drawing inspiration from the “AND” logic principle,^51,52 the tandem combinational logic gate was introduced for enhanced convenience of 6-PTU detection (Fig. 10a). Here, Gate 1 serves as a two-input gate, whereas Gate 2 and Gate 3 function as three-input gates, seamlessly integrating the output signals from preceding logic gates as input signals for subsequent gates. For Gate 1, the output “1” presented only when both conditions of C_6-PTU > 0.3 mM and λ_ex = 336 nm are met simultaneously. Hence, the primary role of Gate 1 is to determine whether the concentration of 6-PTU surpasses 0.3 mM. When Gate 1 receives an input of (1, 0), indicating that the excitation wavelength is 336 nm, and the C_6-PTU concentration is indeed below 0.3 mM, the resulting I₀/I value falls below 2.35 (Fig. 10b), prompting the output of “Low” (Fig. 10c). For the 3-to-1 Gate 2, which incorporates Gate 1's output as an additional input, the tandem logic gate system operates to exclusively yield an output of “1” when all three inputs simultaneously meet the true value condition of (1, 1, 1). Alternatively, if Gate 2 receives an input of (1, 1, 0), signifying that the 6-PTU concentration lies between 0.3 mM and 0.6 mM, the resulting I₀/I values range from 2.35 to 3.07, with the output being “Normal”. Analogously, for the 3-to-1 Gate 3, the operation of the tandem logic gates progresses solely when all three inputs align with the truth value of (1, 1, 1), leading to an output of “1”. This output signifies that the resulting I₀/I values exceed 5.76, triggering the output of “Danger”. Conversely, if the 6-PTU concentration falls within the range of 0.6 mM to 0.9 mM, causing Gate 3's input to be set to (1, 1, 0), the I₀/I values in urine vary between 3.07 and 5.76, resulting in an output of “High”. The truth table in 6-PTU detection is given in Fig. S20 (ESI†). Besides, a similar intelligent detection system for 3-NT has been devised and presented in Fig. S21 (ESI†), accompanied by its truth table in Fig. S22 (ESI†).

Fig. 10 (a) The electronic equivalent circuit utilizing tandem combinational logic gates. (b) Threshold histograms depicting the relative luminescence intensity (I₀/I) for each individual logic gate. (c) Output signals aligned with varying C_6-PTU inputs.

Conclusion

In summary, a robust 3D Ni(II)-MOF, featuring a trinuclear cluster based (3,9)-c xmz porous architecture, was successfully assembled from the chiral ligand of 4,4′-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid and nickel chloride under solvothermal conditions. Based on the spectral overlap and photo-induced electron transfer (PET) caused luminescence quenching response, NiMOF demonstrated remarkable capabilities in the detection of the 3-NT biomarker and 6-PTU thyroid drug in urine samples, with high stability, exceptional selectivity, rapid response, remarkable sensitivity, and low detection limit. Additionally, an intelligent detection system was devised, incorporating tandem combinational logic gates, to enhance the reliability and practicality in urine 3-NT/6-PTU detection. This work offers a viable approach for fabricating MOF-based luminescent sensors, enabling intelligent monitoring of BSMs in real bodily fluids.

Author contributions

Wencui Li: writing – original draft, investigation, data curation. Liying Liu: writing – original draft, investigation. Xiaoting Li: formal analysis; investigation. Hu Ren: formal analysis. Lu Zhang: formal analysis. Mohammad Khalid Parvez: software, funding acquisition. Mohammed S. Al-Dosari: funding acquisition. Liming Fan: writing – review & editing, project administration, funding acquisition. Jianqiang Liu: supervision, writing – review & editing, funding acquisition.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

This work was supported by the Natural Science Foundation of Shanxi Province (No. 202203021211090), Young Academic Leader Supported Program of North University of China (No. QX201904), Postgraduate Innovation Project of Shanxi Province (No. 2024KY600), the Construction Project of Nano Technology and Application Engineering Research Center of Guangdong Medical University (4SG24179G), Key Scientific Research Project of Colleges and Universities of Education Department of Guangdong Province (2020ZDZX2046, 2021ZDZX2052, and 2022ZDZX2022), Guangdong Medical University Research Project (4SG23285G, GDMUZ2023001), the open research fund of Songshan Lake Materials Laboratory (2022SLABFN12), Guangdong Basic and Applied Basic Research Foundation (2023A1515011536) and Graduate Science and Technology Project of North University of China (No. 20231924). Prof. Mohammad Khalid Parvez is grateful to Researchers Supporting Project (RSP2024R379), King Saud University, Riyadh, Saudi Arabia, for financial assistance.

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Footnotes

† Electronic supplementary information (ESI) available: Additional figures, FT-IR spectra, PXRD patterns, TG-DTG curve, and X-ray crystallographic data. CCDC 2370376 for NiMOF. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d4tb01618a

‡ These authors contributed equally to this work.

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