N-Doped TiO2–Carbon Composites Derived from NH2-MIL-125(Ti) for Electrochemical Determination of tert-Butylhydroquinone

Electrochemical determination of tert-butylhydroquinone (TBHQ) is vital to food safety due to negative health effects; however, bare electrode of traditional electrochemical sensors generally has a narrow linear range and low sensitivity, limiting their practical application. Accordingly, the nano-architecture fabricated with N-doped TiO2–carbon nano-composites (TiO2/NC) is prepared by the thermolysis of NH2 functionalized MIL-125(Ti) metal–organic frameworks (NH2-MIL-125(Ti)). TiO2/NC composites are firstly developed as the electrochemical material for electrochemical determination of TBHQ. The TiO2/NC composites with a highly porous structure, excellent conductivity and electron transportation, and large surface area show remarkable electrochemical oxidation ability for TBHQ. Under optimal conditions, TiO2/NC composite-modified electrode presents a broader linear response to TBHQ concentration of 0.05–100 μM with the detection limit as low as 4 nM (S/N = 3). Finally, the sensor platform is implemented directly to determine TBHQ in edible oil for evaluation of its practical application. TiO2/NC composites sensor fabricated perform larger linear range with high sensitivity and anti-interference properties, which can be used as a potential for electrochemical determination of TBHQ.


Introduction
tert-Butylhydroquinone (TBHQ) is one of the common preserving additives in edible oils due to its low price, non-toxicity, and high chemical stability (Sanidad et al., 2016;Almeida et al., 2011). Howbeit, many health studies have shown that its oxidative product is toxic. Excessive use of TBHQ may induce negative health effects like stomach tumors and liver damage (Negar et al., 2007;Eskandani et al., 2014), carcinogenesis (Hirose et al., 1998), and underdevelopment of the reproductive system (Jeong et al., 2005). Therefore, many regions (such as European Union, the USA, and China) have legislated laws and permitted the maximum allowable concentration in food of 200 mg kg −1 (Li et al., 2017). Summarizing the mentioned above, effective measurement of phenolic antioxidants is meaningful for quality control procedures.
Until now, different types of analytical techniques have been widely used in the determination of TBHQ. Electrochemical methods are more suitable than capillary electrophoresis (Boyce et al., 1999) and chromatography (Farajmand et al., 2017) in terms of low cost, fast speed, easy operation, and accuracy. A variety of electrochemical modified materials, including carbon nanotubes (Caramit et al., 2013;Ziyatdinova et al., 2015;Tang et al., 2022), polymers (Tang et al., 2016), and metal oxide nanoparticles (Gan et al., 2016;Cao et al., 2019;Monteiro et al., 2016), have been done to increasing the sensitivity and selectivity for TBHQ.
In some research, transition metal oxides (e.g., TiO 2 and ZnO) as electrochemical materials show facile electron transfer, high biocompatibility, and considerable stability (Arif et al., 2016;Lu et al., 2021;Mahadik et al., 2017). However, the bulk and aggregation of nanostructured TiO 2 during the electrochemical process leads to the decrease of active sites and affects the catalytic performance (Liu et al., 2013). Therefore, it is greatly important to find a suitable supports; carbon materials including carbon nanofiber, porous carbon, carbon nanotubes, and graphene (Zeng et al., 2013;Tang et al., 2021;Qiu et al., 2014;Chen et al., 2011), having advantages of high surface area and electrical conductivity, have been applied as supports to prevent the agglomeration and increase the conductivity and chemical stability of TiO 2 nanomaterials. The interaction between TiO 2 and carbon materials is relatively weak when the TiO 2 /C composites are fabricated by separate steps, because of their relatively low ions/electron transfer (Li et al., 2012;Li et al., 2008). Moreover, nanostructured metal oxides-carbon hybrid composites can be obtained via the solid-state pyrolysis of suitable metal-organic frameworks (MOFs) templates with unique thermal behavior. Metal-organic frameworks (MOFs) are one-, two-, or three-dimensional structures consisting of metal ions or clusters of coordinated organic ligands (Rowsell et al., 2004;Li et al., 2020;Wang et al., 2019). Typical Ti-based MOF, MIL-125(Ti) was firstly fabricated by Dan-Hardi et al. (Dan-Hardi et al., 2009) with high porous, low toxicity, and good stability. Some researchers have developed the application of TiO 2 /C composite through pyrolysis of MIL-125(Ti) in Na-ion batteries and microwave absorption (Shi et al., 2016;. Meanwhile, introducing heteroatoms like nitrogen and sulfur into metal/metal oxide or carbon matrices can increase chemical stability, adsorptive ability, and electrocatalysis activity (Li et al., 2013). It can be easily realized by direct pyrolysis of MOFs with designable organic linkers with specific functional groups or elements such as amidogen and sulfhydryl (Gu et al., 2016). To our best knowledge, N-doped TiO 2 -carbon nano-composites derived from Ti-based MOFs for electrochemical sensors are reported rarely.
Bearing these facts in mind, amino-functionalized titanium MOF (NH 2 -MIL-125(Ti)) was synthesized firstly, and then, a porous nitrogen-doped TiO 2 -carbon hybrid composites (TiO 2 / NC) was fabricated via one-step solid-state pyrolysis in an Ar atmosphere. Based on TiO 2 /NC as electrode material, a new electrochemical sensor was constructed for the high-sensitive detection of TBHQ. The schematic illustration of the TiO 2 /NC/ GCE fabrication process was given in Scheme. 1. The TiO 2 / NC composites with the highly porous structure, excellent conductivity, and electron transportation, high surface area exhibited remarkable electrochemical oxidation ability for TBHQ. In addition, the composite electrode was successfully applied to recognize and determine TBHQ in edible oil.

Reagents and Apparatus
Titanium tetraisopropanolate, tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and 2-aminoterephthalic acid (H 2 BDC-NH 2 ) were achieved from Aladdin Industrial Corporation (China). N,N-Dimethylformamide (DMF) and Scheme 1 The fabrication of TiO 2 /NC sensor and electrochemical determination of TBHQ other chemicals were provided by Sinopharm Chemical Reagent Co., Ltd. Phosphate buffer solution used in this manuscript was prepared by mixing NaH 2 PO 4 ·2H 2 O (0.1 M) and Na 2 HPO 4 ·12H 2 O (0.1 M). All reagents were used without further purification and the solutions were prepared by the hyperpure water with 18.2 MΩ·cm.
Electrochemical experiments were carried out via a CHI 660E electrochemical workstation (Shanghai CH Instruments, China), in which a three-electrode cell was used with the bare or modified GCE (diameter 3 mm; CHI104), the saturated calomel electrode (SCE), and the platinum wire as the working electrode, the auxiliary electrode, and the reference electrode. The morphologies of materials were studied using a JSM-7100F scanning electron microscope and a JEM-100CX electron microscope (JEOL, Japan). Powder X-ray diffraction (XRD) was collected on a Bruker D8-ADVANCE (Bruker, Germany) by using Cu Ka radiation. N 2 adsorption/desorption isotherms were performed at 77 K on an ASAP 2020 analyzer (Micromeritics, Norcross, GA, USA). X-ray photoelectron spectroscopy (XPS) was examined using a K-Alpha spectrometer (Thermo Fisher Scientific Inc., UK).

Fabrication of NH 2 -MIL-125(Ti)
A m i n o -f u n c t i o n a l i z e d T i -b a s e d M O F w i t h (Ti 8 O 8 (OH) 4 (bdc-NH 2 ) 6 (NH 2 -MIL-125) was presented by Kim et.al (Kim et al., 2013). A solution of 2-aminoterephthalic acid (2.54 g) in 60 mL of DMF-CH 3 OH (9:1, v/v) mixture was prepared. Then, titanium (IV) isopropoxide (3.19 mL) was added to the above solution. The above solution was transferred into a Teflon-lined autoclave at 150 °C for 24 h in an oven. Next, the yellow solid powder was recovered by filtration and washed several times with DMF and CH 3 OH. Finally, NH 2 -MIL-125 was dried under vacuum at 80 °C in the oven.

Preparation of Nitrogen-Doped TiO 2 -Carbon Hybrid Composites (TiO 2 /NC)
For the TiO 2 /NC composite preparation, the as-obtained NH 2 -MIL-125(Ti) was firstly pre-carbonized at 300 °C for 2 h in a tube furnace and then further carbonized at 900 °C for 2 h with a speed of 2 °C/min under Ar atmosphere to make the material fully carbonized. The black powder of TiO 2 /NC composites was collected.

Preparation of the Modified Electrode
The detailed preparation of the TiO 2 /NC-modified electrode was described as follows: firstly, the bare glassy carbon electrode (GCE) was carefully polished with 0.05 μm alumina power. Subsequently, GCE was cleaned with ethanol and ultrapure water for 1 min successively. Finally, it was dried with nitrogen at room temperature. Four milligrams of TiO 2 / NC composites was dispersed in 2 mL DMF by sonication to obtain a homogeneous suspension. Nine microliters of the above suspension was dropped onto the bare GCE surface and dried at room temperature to obtain TiO 2 /NC/GCE. In contrast, NH 2 -MIL-125(Ti)-modified electrode was prepared in a similar process.

Characterization of TiO 2 /NC Composites
In the first stage, the Ti-based MOF was synthesized via Ti 4+ and 2-aminoterephthalic acid complexation process. Then, the TiO 2 /NC composites were fabrication by the solid carbonation of the NH 2 -MIL-125(Ti) process. Octahedral-like structures of both NH 2 -MIL-125(Ti) and TiO 2 / NC composites were presented by TEM and SEM ( Fig. 1). As revealed by SEM images ( Fig. 1a and b), the precursor NH 2 -MIL-125(Ti) showed an octahedral shape morphology with a smooth surface, the calcination process resulted in N-doped carbon particles in the range of ~ 500-1000 nm with a rough surface. Furthermore, as depicted in Fig. 1c and d, TEM images revealed that TiO 2 nanoparticles were uniformly distributed in the carbon matrix, which was verified by energy-dispersive spectroscopy (EDS) and elemental mapping analysis of C (red), N (green), O (cyan), and Ti (purple) (Fig. 1e-i).
The XPS spectra of TiO 2 /NC were further analyzed, as shown in Fig. 2b. The wide XPS survey spectra revealed the presence of Ti-, C-, N-, and O-related peaks. The peaks at a binding energy of 458.2 and 463.9 eV were belonged to Ti 2p 3/2 and Ti 2p 1/2 (Fig. 2c), indicating the presence of TiO 2 species. Additionally, the binding energy peak was observed at 400.8 eV, which represented the typical The a XRD patterns of NH 2 -MIL-125(Ti) and TiO 2 /NC composites, XPS spectra of the synthesized TiO 2 /NC composites: b survey spectrum and c Ti 2p, d BET analyses of TiO 2 /NC composites, inset: BJH pore size distribution binding energy of the pyrrolic nitrogen (Casanovas et al., 1996). Figure 2d showed the nitrogen adsorption − desorption isotherms of TiO 2 /NC. The isotherm exhibited a type IV isotherm curve, indicating the TiO 2 /NC was a typical mesoporous material. The carbonized sample TiO 2 /NC showed the BET surface area of 287.9 m 2 ·g −1 and pore diameters of 2.95 nm. Therefore, TiO 2 /NC showed a relatively large surface area and pore diameter. Basically, porous materials with larger pores have excellent advantages for catalysis due to their active sites which rapidly are accessed by any substrate for high reactivity (Corma et al., 1996).

Characterization of TiO 2 /NC-Modified Electrode
Electrochemical characterization of the TiO 2 /NC-modified electrode was also studied by the cyclic voltammetric (CV) technique. As seen in Fig. 3a, the CV curves of 5.0 mM [Fe(CN) 6 ] 3−/4− containing 0.1 M KCl over bare GCE, NH 2 -MIL-125(Ti)/GCE, and TiO 2 /NC/GCE. A pair of oxidation-reduction peaks appeared at the bare GCE with the anode peak current I pa about 48.56 μA. On NH 2 -MIL-125(Ti) coated on the surface of GCE, the peak currents obviously increased owing to the high surface area with the anode peak current value of 72.06 μA. Moreover, on TiO 2 /NC/GCE, a pair of well-defined peaks appeared with an I pa (81.76 μA) of almost 2 times higher than bare GCE, indicating that the TiO 2 /NC sensor had a fast electron transfer rate because of the highly porous structure, excellent conductivity and electron transportation, large surface area of the TiO 2 /NC composites.
As shown in the inset of Fig. 3a, the peak currents of three different electrodes increased linearly related to the square root of the scan rate. According to Randles-Sevcik equation: where I p , n, A, C 0 , D 0 , and v are the peak current, the number of transfer electrons (n = 1), the electrochemically (1) I p = 2.69 × 10 5 n 3∕2 AD 1∕2 0 C 0 v 1∕2 active area, the concentration of the reactant, the diffusion coefficient of the [Fe(CN) 6 ] 3−/4− (about 7.6 × 10 −6 cm 2 ·s −1 ), and the scan rate, respectively. The slopes were 69.39, 157.3, and 230.2 of the three lines at bare GCE, NH 2 -MIL-125(Ti)/ GCE, and TiO 2 /NC/GCE, respectively. According to the slopes of the linear equations, the electroactive surface areas of bare GCE, NH 2 -MIL-125(Ti)/GCE, and TiO 2 /NC/GCE were calculated to be 0.026 cm 2 , 0.070 cm 2 , and 0.086 cm 2 , respectively. Their results clearly indicated that TiO 2 /NC could effectively enlarge the electroactive area and more reactive sites.
The impedance spectroscopy of the different electrodes (bare GCE, NH 2 -MIL-125(Ti)/GCE, and TiO 2 /NC/GCE) in 5.0 mM [Fe(CN) 6 ] 3−/4− containing 0.1 M KCl was depicted in Fig. 3b. The impedance of the bare GCE was relatively large with the value of 500 Ω. The electrode prepared after coated NH 2 -MIL-125(Ti) exhibited lower impedance (almost 200 Ω) attributed to the porous structure of NH 2 -MIL-125(Ti), which can improve the charge transfer efficiency. Again, corresponding to the TiO 2 /NC/GCE, the impedance value was further reduced to only 10 Ω. This change implied that the charge transfer rate was obviously increased after the carbonization of NH 2 -MIL-125(Ti), thereby making enhancement in conductivity of this TiO 2 / NC sensor.

Electrochemical Behaviors of TBHQ
The electrochemical responses of TBHQ (100 μM) were investigated individually applying CV over bare GCE, NH 2 -MIL-125(Ti)/GCE, and TiO 2 /NC/GCE. The CV curves were documented in Fig. 4a. In well-defined redox peaks obtained at bare GCE and various modified electrodes, bare GCE exhibited the lowest peak currents (I pa = 1.32 μA) with the largest peak-to-peak separation (ΔE p = 182 mV). Furthermore, at NH 2 -MIL-125(Ti)/ GCE, high redox peak currents (I pa = 4.08 μA) with ΔE p of 88 mV were found, due to the porous structure of NH 2 -MIL-125(Ti) with enhanced surface areas. Additionally, at TiO 2 /NC/GCE, the oxidation current (I pa = 30.58 Inset: the Randle equivalent circuit μA) further increased 23.2 times that of bare GCE. Meanwhile, the ΔE p (55 mV) of TBHQ on TiO 2 /NC/GCE was much smaller than those on the other electrodes, suggesting that TiO 2 /NC/GCE had the best electron transfer kinetics for the redox of TBHQ. Thus, TiO 2 /NC composites enabled excellent electrochemical catalytic activity for TBHQ oxidation.

Optimization of the pH Value
The effect of the supporting electrolyte pH value (varied from 4.0 to 9.0) in the electrochemical reaction of TBHQ on the TiO 2 /NC sensor applied using CV was depicted in Fig. 4b. The oxidation peaks of TBHQ (50 μM) in phosphate buffer solution (0.1 M) shifted to the negative potential signal as the pH increased (Fig. 4c), due to the protons involved in the electrochemical reactions of TBHQ (Ziyatdinova et al., 2020). A good linear relationship between pH and anodic potential was revealed in Fig. 4c, E p = 0.3869-0.0554 pH (R 2 = 0.991). The slope was 55.4 mV per pH closed to the theoretical value (59 mV per pH at 298 K), indicating that the number of electrons was equivalent to the number of protons involved in the redox process of TBHQ (Ziyatdinova et al., 2020). Moreover, the acidity of phosphate buffer solution also had a remarkable effect on peak current values of TBHQ. The oxidation peak currents increased with the increase of pH values until they reached the maximum pH value of 7.0 and then decreased when the pH value was further increased. The maximum peak current of TBHQ was achieved at a neutral solution owing to the proton groups of TBHQ which contributed to the reduction of the hydroxyl bond energies so as to improve electron transfer through O-H⋯N (Ding et al., 2005). Therefore, the pH value of the phosphate buffer solution was set to 7.0. Fig. 4 The a CVs of 100 μM TBHQ on bare GCE, NH 2 -MIL-125(Ti)/GCE, and TiO 2 /NC/GCE in 0.1 M phosphate buffer (pH 7.0) at a scan rate of 100 mV·s −1 . b CVs of 50 μM TBHQ on TiO 2 / NC/GCE with a different pH (4.0-9.0). c pH versus peak current and potential. d CVs of 50 μM TBHQ on TiO 2 /NC/ GCE at various scan rates (from 20 to 400 mV·s. −1 ). e Plots of I pa /I pc versus v, inset: plot of lg I pa versus lgv. f Plots of E pa /E pc of TBHQ versus lgv

Kinetics Studies
The CV curves of TiO 2 /NC/GCE (Fig. 4d) were investigated at various scan rates (20-400 mV·s −1 ) to analyze the kinetic process. As seen in Fig. 4e, it is clear that both I pa and I pc of TBHQ increased gradually with scan rates ranging from 20 to 400 mV·s −1 , and the equations satisfy: I pa (μA) = 1.5299 v 1/2 (V·s −1 ) − 2.9653(R 2 = 0.998) and I pc (μA) = − 1.3797 v 1/2 (V·s −1 ) + 3.4657 (R 2 = 0.997). In addition, the logarithm of anodic peak current (lgI pa ) vs the logarithm of v (lg v) (the inset of Fig. 4e) was linear. The linear equation was lgI pa (μA) = 0.542 lgv (V·s −1 ) + 0.0157 (R 2 = 0.997) with the slope value of 0.54, which was close to 0.5. The results manifested that the electrochemical behavior on the surface of TiO 2 /NC/GCE was controlled by the diffusion of TBHQ (Chen et al., 2021).
Additionally, the anodic (E pa ) and cathodic (E pc ) peak potential vs the natural logarithm of v (lg v) of TBHQ (Fig. 4f) were linear ranging from 120 to 400 mV s −1 and obtained the slope values of 0.0747 and − 0.0531, according to the following equations (Laviron, 1979): where R-molar gas constant (J mol −1 K −1 ), T-the absolute temperature (K), and F-the Faraday's constant (C mol −1 ). Thus, the electron transfer number (n) and the transfer coefficient (α) were calculated to be 1.87 (close to 2) and 0.58, respectively. The result denoted that the two-proton and two-electron process was involved in the electro-oxidation of TBHQ on TiO 2 /NC/GCE.
The electron transfer rate constant (k s ) was calculated based on Eq. (4): (2) where n is electron transfer number of 2, ν is the scan rate of 100 mV·s −1 , and ΔE P = 51 mV. Also, k s can be calculated as 0.63 s −1 . The electron transfer rate constant (k s ) of TiO 2 / NC/GCE was larger than the reported electrode (Wang et al., 2021), indicating that this modified electrode had a higher catalytic capacity to promote electron transfer of TBHQ.

Analytical Performance of TiO 2 /NC/GCE to TBHQ
Quantitative analysis was examined to determine TBHQ using the higher sensitive technique of differential pulse voltammetry (DPV) on TiO 2 /NC/GCE. As shown in Fig. 5a, the DPV curves for various concentrations of TBHQ were given on TiO 2 /NC/GCE in 0.1 M phosphate buffer (pH 7.0). The catalytic current increased gradually with the concentration of TBHQ in the range of 0.05-100 μM and the linear equations were I pa (μA) = 2.257C (μM) + 2.886 (R 2 = 0.993, range of concentration was 0.05-10 μM) and I pa (μA) = 0.5886C (μM) + 19.54 (R 2 = 0.995, range of concentration was 10-100 μM), respectively. The detection limit (LOD) of 4 nM (S/N = 3) was superior to those of the previously reported TBHQ sensors (Table 1). Hence, such outstanding analytical performance was ascribed to the specific

Reproducibility, Stability, and Interferences Studies
To measure the reproducibility of TiO 2 /NC/GCE, five aforementioned TiO 2 /NC electrodes were used to detect 10-μM TBHQ by the DPV method. The reasonable relative standard deviation (RSD) of peak currents about 2.5% was exhibited, concluding that TiO 2 /NC sensor had excellent reproducibility. Also, the long-term stability of the TiO 2 /NC sensor was checked by intermittent detection of TBHQ. The peak currents for 10 μM TBHQ were maintained at 98.3% and 97.9% of the initial current after 5 days and 15 days, verifying the prominent long-term stability of the modified electrode.
The selectivity of the TiO 2 /NC/GCE was further evaluated, the impacts of some organic analytes (tenfold concentration of glucose, twofold concentration of L-aspartic acid and ascorbic acid, onefold concentration of butylated hydroxyanisole), and various ions (50-fold concentration of K + , Na + , Mg 2+ , Ca 2+ ) on the current signals of TBHQ was investigated by the I-t method with the 10 μM TBHQ. Furthermore, twofold concentrations of hydroquinone were selected as interference to evaluate selectivity owing to its similar structure with TBHQ. Although hydroquinone had a high electrochemical response, its oxidation potential differed from TBHQ on TiO 2 /NC/GCE. As shown in Fig. 5b, these additives did not affect the amperometric current response of TBHQ, implying that TiO 2 /NC/GCE was suitable for the selective determination of TBHQ.

Analysis in Real Sample
To assess the practical potential of the proposed method, the TiO 2 /NC/GCE was applied to detect TBHQ in edible oil (soybean oil and colza oil). Briefly, 5.0 g of the samples were dissolved in 50 mL of ethanol and centrifuged at 3000 rpm for 20 min; then, the extract procedure was repeated four times. Two hundred microliters of soybean oil or sesame oil samples was respectively diluted to 10 mL of 0.1 M phosphate buffer (pH 7.0) and analyzed by a standard addition method (n = 3) using the DPV technique. The results were listed in Table 2. The recoveries were ranged from 98.5 to 101.2% with the RSD values below 5%. Meanwhile, the obtained results matched well with the HPLC method. All results validate the TiO 2 /NC/GCE can be applied in the measurement of TBHQ in edible oil samples.

Conclusion
We have successfully constructed N-doped TiO 2 -carbon nano-composites by the pyrolysis of NH 2 -MIL-125(Ti). The novel TiO 2 /NC sensor exhibited enhanced electrocatalytic ability towards TBHQ oxidation with a low detection limit and large detection range. The excellent performance of TiO 2 /NC composites benefited from synergetic advantages of the highly porous structure, large surface area, excellent conductivity, and electron transportation. Moreover, the constructed TiO 2 /NC sensor has been efficiently used to monitor TBHQ in real oils. This facile strategy may provide a valuable reference to fabricate other MOF-based material sensors.
Funding This work was supported by the National Natural Science Foundation of China (21904004), the Top-Notch Talent Program for Outstanding Young Talents of Anhui Province (gxbjZD2021070), the stable talent program of Anhui Science and Technology University, and the Student's Platform for Innovation and Entrepreneurship Training Program of China (202010879047).

Data Availability
The authors declare that all data supporting the findings of this study are available within the article and its supplementary information file.