Metal–Organic Frameworks for Electrocatalytic Sensing of Hydrogen Peroxide

The electrochemical detection of hydrogen peroxide (H2O2) has become more and more important in industrial production, daily life, biological process, green energy chemistry, and other fields (especially for the detection of low concentration of H2O2). Metal organic frameworks (MOFs) are promising candidates to replace the established H2O2 sensors based on precious metals or enzymes. This review summarizes recent advances in MOF-based H2O2 electrochemical sensors, including conductive MOFs, MOFs with chemical modifications, MOFs-composites, and MOF derivatives. Finally, the challenges and prospects for the optimization and design of H2O2 electrochemical sensors with ultra-low detection limit and long-life are presented.


Introduction
Hydrogen peroxide (H 2 O 2 ) is an indispensable component in living organisms as a biological intermediary, and has been widely applied as an essential reagent in daily life, industrial fields, medical treatment, and other sections. However, a high concentration of H 2 O 2 is corrosive and can cause serious injury when contacts with the skin, and accidental ingestion of H 2 O 2 can result in gas embolism in several organs, especially in heart, lung and esophagus [1][2][3][4]. The strong oxidizing property of H 2 O 2 can even be applied for the preparation of explosives, which may threaten people's lives [5,6]. More importantly, the harm caused by low-concentration H 2 O 2 should not be underestimated. Actually, trace amounts of H 2 O 2 produced in the cells can cause the induced oxidation of melanocytes, resulting in the death of melanocytes, which is also the main cause of vitiligo [7]. Abnormal production of H 2 O 2 in mitochondria can cause reversible mitochondrial swelling, rupture and cellular structural changes, which can induce diseases such as diabetes, Parkinson's diseases and cancers [8]. Therefore, it's of great significance to detect low concentration of H 2 O 2 .
For now, a great number of H 2 O 2 detection approaches, such as electrochemical detection [9], fluorescence [10], titration [11] and chromatography [12] have been employed in detecting H 2 O 2 concentration. However, traditional methods are no longer applicable in many fields with the higher requirements for H 2 O 2 detection. For instance, precision data and low detection limit can be obtained through fluorescence detection, while high detection cost and requirement of sample preparation remain a problem [13]. Compared with fluorescence detection method, the colorimetric detection method itself has the advantages of low cost and fast detection speed. However, the raw materials can be easily denatured which makes it difficult to prepare [14]. In contrast, electrochemical detection method has been widely used owing to its advantages of simplicity, rapidity, sensitivity and economy [15,16]. Despite that, electrochemical H 2 O 2 detection usually requires a higher potential for direct reduction or oxidation on the surface of the bare electrode, resulting in a less current response. Therefore, it is essential to improve the bare electrode or design new electrode materials to increase the sensitivity of the H 2 O 2 sensor and speed up the response time for the detection of ultra-low concentration of H 2 O 2 [17].

Research Status and Challenges
Hitherto, various strategies have been reported to modify the electrodes. Among them, the most common one is to prepare the metal oxide modified electrodes. It has been observed that the electrocatalytic materials containing Fe 2 O 3 show excellent catalytic performance, where the detection limit reaches 5 nmol, and they can be applied to detect H 2 O 2 both inside and outside the cells [18][19][20]. Apart from Fe 2 O 3 , Cu 2 O features high specific surface area, good electrochemical activity and the potential to promote electron transfer reactions at a lower overpotential, making it a favorable material for the development of H 2 O 2 sensors. Nevertheless, the catalytic activity is affected by the particle size and the shape of the metal oxides. On the whole, the large particle size and irregular morphology reduce the effective contact between the catalytic materials and the H 2 O 2 molecules, resulting in incomplete catalytic activity and reduced catalytic effect [21,22]. Additionally, enzymes are often used to modify the electrodes due to their perfect selectivity for H 2 O 2 . Horseradish peroxidase (HRP), as one of the most common H 2 O 2 enzymes, although has been extensively studied and used for manufacturing H 2 O 2 sensors [23], its application has been restricted by the complex immobilization process and the instability during the detection [24]. Currently, precious metal nanoparticles (Pt, Ag, Ru et al.) have been widely implemented in H 2 O 2 detection technology due to their unique electronic structure, prominent physical and chemical properties [25]. For instance, AuNCs (nanoclusters) is an emerging nanomaterial that exhibits excellent performance and can improve the sensitivity of H 2 O 2 detection [26]. B. Patella and co-workers designed the rGO/Au-NPs (nanoparticles)-based electrode through a three-electro deposition method to monitor H 2 O 2 released by the human macrophages [27]. However, considering the scarcity of precious metals, it is necessary to find and develop new materials with low cost and high catalytic activity to replace precious metals [28,29].
In recent years, numerous new materials have also been used for electrochemical detection of H 2 O 2 , such as CNTs (carbon nanotube), graphene and metal organic frameworks (MOFs) [30][31][32]. As we know, the electrical conductivity and catalytic performance can be improved by the carbon coating method; when the graphene oxide nanoflake is covered by nano-scale graphene, the subsequently synthesized graphene oxide/graphene composite material presents a better performance on H 2 O 2 detection with high catalytic activity and electrochemical stability [33]. Yu et al. [34] developed a novel/graphene (NiO/GR) nanocomposite that exhibited high sensitivity to H 2 O 2 , the GR coating improved the electrochemical stability and its anti-interference ability. MOFs have drawn increasing interest and been applied to gas storage/separation [35][36][37][38][39][40][41][42][43][44], drug delivery [35][36][37][38][39][40][41][42][43][44], energy storage/conversion [35][36][37][38][39][40][41][42][43][44] and multiphase catalysis [35][36][37][38][39][40][41][42][43][44] due to their tunable pore sizes, diverse structures, and abundant functional designs [35][36][37][38][39][40][41][42][43][44]. Moreover, the ordered arrangement of metal sites and organic ligands provide abundance of accessible catalytic sites and confer intrinsic enzyme-mimetic properties to MOFs compared to other types of nanozymes [45]. For example, Zhang [46] developed the new class of 2D conductive MOFs films [Co 3 (HHTP) 2 ] n by LB (langmuir-blodgeet) technology. The porous structures and exposed Co active sites from the [Co 3 (HHTP) 2 ] n had superior catalytic activity for H 2 O 2 . In addition, some MOFs with mesh structures can be used as carriers for other materials to form composite materials with new functions [46]. There have been several review reports on the use of MOFs for H 2 O 2 sensors [45,[47][48][49][50][51][52], for example, Li et al. [45,[47][48][49][50][51][52] classified MOFs into four categories and reviewed the progress of MOFs in chemical sensors, includ-ing the detection of H 2 O 2 . Goncalves et al. [45,[47][48][49][50][51][52] reviewed the development of MOFs derivatives for sensors. However, most of these reports are not comprehensive enough to introduce all of the types of MOFs-based H 2 O 2 sensors. What' more, instead of focusing on H 2 O 2 detection, variety of molecules are also included, which makes most of these reviews not deeply explore the mechanism of MOFs for H 2 O 2 sensing, as well as the design and development of MOFs H 2 O 2 electrochemical sensors. In this paper, based on the reviews of the same topic, as well as the latest research progress, we found that MOFs can exert more structural advantages in electrochemical detection of H 2 O 2 (strong adsorption, faster electron transport, and high conductivity) and become more competitive as a sensor. Here, we deeply explore the detection mechanism of electrochemical H 2 O 2 for different types of MOFs, some bright ideas for the design and improvement of MOFs-based electrochemical H 2 O 2 sensors are proposed based on the recent research progress. Firstly, the sensing mechanism and working principle of MOFs-based H 2 O 2 electrochemical sensors are distinctly introduced. Secondly, as shown in Figure 1, we categorize the recent reported MOFs-based H 2 O 2 electrochemical sensors as: (1) High electrical conductivity is vital to electron transfer in the process of H 2 O 2 splitting. In general, the electrical conductivity of MOFs depends on the carrier mobility and internal charge density. The π-conjugated structure forms a continuous conductive network to facilitate the conduction of electrons. In addition, high-energy electrons or holes in metal ions can induce high concentrations of loosely bound carriers, thereby increasing the charge density. The direct connection between the metal nodes and the organic ligands can effectively reduce the energy mismatches and further promote the charge delocalization and electron transfer.

(ii) Activity
The catalyst activity is an important factor in the decomposition rate of H 2 O 2 . It is mainly related to the intrinsic catalytic ability and the number of active sites of the catalyst. Generally, the porous structure can not only increase the specific surface area, but also expose more active sites to improve the catalytic activity, thus further improve the adsorption capacity, reduce the activation energy of the intermediate product transformation.

(iii) Selectivity
An ideal electrochemical sensor for H 2 O 2 should have high selectivity. For example, H 2 O 2 samples may be mixed with other substances (glucose, ascorbic acid, ethanol, etc.), and they will also undergo redox reactions. Therefore, the sensors should only respond to H 2 O 2 at a specific voltage.
(iv) Stability The commercial H 2 O 2 electrochemical sensors must possess excellent chemical and structural stability in hostile acidic and alkaline environments. In specific cases, it may suffer from changes in catalyst structure and reduced catalytic activity due to the particle agglomeration during the long-time detection process. Therefore, in order to ensure the accuracy of the test, especially in medical clinical applications, the requirement of high stability need be met in the design of commercialized sensors.
(v) Low-cost Precious metal electrocatalysts (e.g., Pt, Au, Ag, Pd) have high catalytic activity, but their scale-up application is limited by high cost, limited reserves, poor stability, low sensitivity and selectivity. Alternatively, MOFs-based catalysts are commonly ligated with transition metals, which have inherently good catalytic activity and can be feasibly prepared by simple methods (hydrothermal method, ultrasonic method et al.). Thus, in order to meet the goal of commercial development, the raw materials and preparation methods of the H 2 O 2 electrochemical sensors should follow the principles of low cost and low time consumption.
(vi) Environmental-friendly The concept of low-carbon green development is of great significance to the sustainable development of human society. Specifically, the raw materials for the H 2 O 2 electrochemical sensors should be non-toxic and non-polluting. The preparation process should not produce hazardous gases and solutions. What's more, the catalysts must be non-hazardous to the cells, in order to meet the medical detection requirements. accuracy of the test, especially in medical clinical applications, the requirement of high stability need be met in the design of commercialized sensors.
(v) Low-cost Precious metal electrocatalysts (e.g., Pt, Au, Ag, Pd) have high catalytic activity, but their scale-up application is limited by high cost, limited reserves, poor stability, low sensitivity and selectivity. Alternatively, MOFs-based catalysts are commonly ligated with transition metals, which have inherently good catalytic activity and can be feasibly prepared by simple methods (hydrothermal method, ultrasonic method et al.). Thus, in order to meet the goal of commercial development, the raw materials and preparation methods of the H2O2 electrochemical sensors should follow the principles of low cost and low time consumption.
(vi) Environmental-friendly The concept of low-carbon green development is of great significance to the sustainable development of human society. Specifically, the raw materials for the H2O2 electrochemical sensors should be non-toxic and non-polluting. The preparation process should not produce hazardous gases and solutions. What's more, the catalysts must be non-hazardous to the cells, in order to meet the medical detection requirements.

Electrochemical Sensor Detection Principle
Generally, the electrochemical detection of H 2 O 2 is achieved by applying a corresponding voltage to the electrochemical sensor, followed by the oxidation or reduction of H 2 O 2 on the electrode surface. The electric charges of the redox process are captured by the electrode and converted into an electrochemical signal. Qualitative and quantitative analysis of H 2 O 2 can be obtained through the change in the peak voltage and current. The schematic diagram of electrochemical detection of H 2 O 2 is shown in Figure 2. Commonly, H 2 O 2 detection is performed under neutral or alkaline conditions, with certain differences in the reaction mechanism. Specifically, the difference lies in whether the catalyst produces a reducing or oxidizing effect on H 2 O 2 during the detection: if the catalyst appears in an oxidized state, the H 2 O 2 is oxidized; and if the catalyst is in a reduced state, the H 2 O 2 is reduced. We will discuss the specific steps of H 2 O 2 catalytic decomposition in the following sections.

Electrochemical Sensor Detection Principle
Generally, the electrochemical detection of H2O2 is achieved by applying a corresponding voltage to the electrochemical sensor, followed by the oxidation or reduction of H2O2 on the electrode surface. The electric charges of the redox process are captured by the electrode and converted into an electrochemical signal. Qualitative and quantitative analysis of H2O2 can be obtained through the change in the peak voltage and current. The schematic diagram of electrochemical detection of H2O2 is shown in Figure 2. Commonly, H2O2 detection is performed under neutral or alkaline conditions, with certain differences in the reaction mechanism. Specifically, the difference lies in whether the catalyst produces a reducing or oxidizing effect on H2O2 during the detection: if the catalyst appears in an oxidized state, the H2O2 is oxidized; and if the catalyst is in a reduced state, the H2O2 is reduced. We will discuss the specific steps of H2O2 catalytic decomposition in the following sections.

Detecting under Alkaline Condition
Under alkaline conditions, the catalytic decomposition of H2O2 mainly depends on the redox changes of metal sites. In the first case, the catalyst combines with OHto form intermediates with higher valence state of the metal sites and electrons, then the intermediates react with H2O2 to return to the original valence state, and H2O2 is decomposed. The mechanism can be illustrated by the following equation [80]: The other situation is that H2O2 is adsorbed by catalysts, then the catalysts are reduced as the cathode. After that, the pre-adsorbed H2O2 is decomposed by electron transfer with the catalyst. The mechanism can be illustrated by the following equation [80]:

Detecting under Alkaline Condition
Under alkaline conditions, the catalytic decomposition of H 2 O 2 mainly depends on the redox changes of metal sites. In the first case, the catalyst combines with OH − to form intermediates with higher valence state of the metal sites and electrons, then the intermediates react with H 2 O 2 to return to the original valence state, and H 2 O 2 is decomposed. The mechanism can be illustrated by the following equation [80]: The other situation is that H 2 O 2 is adsorbed by catalysts, then the catalysts are reduced as the cathode. After that, the pre-adsorbed H 2 O 2 is decomposed by electron transfer with the catalyst. The mechanism can be illustrated by the following equation [80]:

Detecting under Neutral Condition
It has been reported that the catalytic decomposition of H 2 O 2 occurs in the presence of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ions. The generation of reactive hydroxyl radicals (HO·) is based on the classical Haber Weiss mechanism/Fenton-type reaction [81][82][83][84] range of 3-4, while ferric ions have better catalytic activity at a neutral pH. The reactivity study of ferric ions show that the coordinated ferrous ions catalyze the decomposition of H 2 O 2 more effectively than the free ferric ions at the neutral pH [82]. In this case, the ferric ions are first reduced into ferrous, and then the ferrous ions are oxidized by H 2 O 2 to turn to ferric ions. The electrochemical mechanism of general Fe-MOFs based materials in neutral media are as follows [85]:

Design and Synthesis of MOFs Based H 2 O 2 Sensor
MOFs are a kind of porous polymer materials connected by metal ions through organic bridge ligands, which combine the advantages of inorganic, organic porous materials and porous hybrids [86][87][88][89]. The structural diversity makes some MOFs possess the multichannel structures which can enhance the electrolyte transport capacity and further increase the electrical conductivity. Furthermore, the reactants can be easily trapped and adsorbed by various active sites and high specific surface areas, thus the conversion of the reaction is facilitated [90]. Therefore, MOFs have great prospect for the preparation of H 2 O 2 sensors. In the following sections, some reliable ideas to flexibly apply MOFs materials to the design of H 2 O 2 sensors are expounded.

Conductive MOFs Based H 2 O 2 Sensor
Ionic conduction and electron conduction occur along with the H 2 O 2 decomposition in the process of detection. However, the conversion efficiency between electrical and chemical energy will be reduced if the conductive orbit cannot be effectively constructed, and leading to decreasing adsorption and catalytic capacity [91]. In general, the formation of conductive network requires coordination interaction between metal ions and organic ligands. Ligands with π-conjugated structures can form a continuous conductive network to facilitate electron conduction. High concentration of loose carriers formed by high-energy electrons or holes in metal ions can increase charge density [91]. The direct connection between metal nodes and organic ligands (such as N, O, S-based ligands) can effectively reduce the energy mismatch, further promoting the charge delocalization and electron transport [92][93][94]. Based on the charge transfer mode, the conductive mechanism of conductive MOFs can be divided into three types as follow: charge transfer "through space", through-bond conduction and through-guest conduction [95].
Aromatic hydrocarbons are a class of compounds with conjugated structures, such as 2,3,6,7,10,11-hexaiminotriphenylene (HITP), 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) and benzenehexol (HOB). These π-conjugated aromatic systems are capable of cooperating with metal nodes to dominate the conduction process. The π-π interaction between the systems and metals facilitates both "through-bond" and "through-space" electronic conduction [96,97]. Our group [36] designed the 2D [Co 3 (HOB) 2 ] n conductive MOF nanosheets with abundant nanoscale channels. HOB and Co 2+ ions were coordinated at the water-air interface to form a single-layer nanosheets with high structural order through LB method (Figure 3a). [Co 3 (HOB) 2 ] n nanosheets were arranged in a long-range order, and then the π-π stacks in the internal pores were formed by original growth on the FTO (fluorine-doped tin oxide) glass. Meanwhile, the coordination of Co-O reduced the energy mismatch, facilitated the charge delocalization and electron transport. The counterion pair generated from electrostatic interactions leads to the feasible electronic adjustment and migration [98,99]. More importantly, the porous structure for proton transport and the exposed metal sites equip the 3-layer nanosheets with excellent reducibility to H 2 O 2 with a LOD (limit of detection) of 3.08 nM (Figure 3b concluded that the common drugs and ion concentration had no impact on H 2 O 2 detection. Noticeably, the activity of [Co 3 (HOB) 2 ] n exhibited almost no attenuation after 1000 CV cycles (Figure 3c). Park [80] et al. reported a Co-based 2D conductive MOF, Co-HAB. The high conductivity (1.57 S cm −1 ), porosity and high density of redox active sites of Co-HAB provided a possibility for ion storage and energy conversion, which may improve the catalytic activity when used for H 2 O 2 reduction. At the same time, excellent chemical and thermal stability increase the utility of sensors. This offers a bright future for the preparation of H 2 O 2 sensors with low detection limit. then Cu 2+ is oxidized to Cu 3+ ; secondly, H2O2 molecules react with Cu 3+ and then they are reduced to form O2 due to the strong oxidizing from Cu 3+ .
Conductive electrical system consisted of metal ions and ligands with π-conjugate structure solve the serious poor conductivity issue for H2O2 electrocatalysts; furthermore, the porous structure is conducive to promoting the mass transfer, and improving the catalytic rate of H2O2 decomposition. Still, the high price of organic ligands remains a large obstruction on the pathway to large-scale commercialization.

Chemically Modified MOFs Based H2O2 Sensor
Chemical modification is a feasible and effective way to introduce desired functions into MOFs materials. In general, MOFs can be functionally modified by their metal sites and/or organic linkers. For example, through the hybridization with conducting polymers, the electrical conductivity of the material can be improved [45,110].
Combining MOFs with conductive species can improve electronic conductivity, catalytic activity, and expand applications. The most common method is to combine the active component with carbon-based materials such as carbon nanotubes and ketone black carbon [111]. POMs (polyoxometalates), with internal unconventional molecular structure, stable physical/chemical properties and redox state, have shown superb activity in fabricating electrocatalysis. When they are used to prepare MOFs, the latest material POM-based MOFs (POMOFs) performed high specific surface and exposed more active sites [29,112,113]. However, the low conductivity reduces the catalytic activity of POMOFs as catalysts, resulting in low sensitivity and high detection limits when applied for H2O2 detection. Wang et al. [58] developed POM-based MOF (NENU5 (polyoxometalate-based metal-organic framework)) grown in situ on KB by adopting a facile and feasible one-step solution method (Figure 4a). The low detection limit (1.03 μM) of NE-NU5-KB-3 for H2O2 is mainly attributed to the high conductivity of KB and the high catalytic activity of NENU5. It also had a wide linear range from 10 μM to 50 mM and a high sensitivity of 33.77 μA mM −1 . More notably, the residual current decreased by ~9% after continuous testing in 30 μM H2O2 for 4 h. It indicated NENU5-KB-3 had good structural stability and stable catalytic activity. Furthermore, drug resistance results have revealed Coordination bonds composed of metals and organic ligands with matched energy levels and good orbital overlap can generate long-distance charges transfer path, which is beneficial for improving the charge transfer [100]. Liu [55] reported an advanced FePc (iron phthalocyanine) -based diyne-linked (−C≡C−C≡C−) conjugated polymers 2D NSs (nanosheets) (FePc-CP NSs) (Figure 3d). It has been demonstrated that the high reduction activity of the catalyst for H 2 O 2 detection (LOD was 0.017 µM) is mainly attributed to the following points: (1) FePc is beneficial to promote the cleavage of O-O bonds between O 2 and peroxide and thereby accelerates the decomposition of H 2 O 2 ; (2) diyne-linked (−C≡C−C≡C−) conjugated structure enhances the conductivity; (3) highly exposed hemelike active centers in layered pore junctions increase catalytic activity. FePc-CP NSs accurately detected H 2 O 2 in beer and orange juice with a recovery of 95.8~107% (Figure 3e), this showed that the FePc-CP NSs had the potential to detect the H 2 O 2 in food. Since then, we can conclude that long-range ordered nanochannels formed by the accumulation of 2D π-conjugates can realize the electrolyte transport. This approach to creating the charge transport by using covalent bonds of extended coordination polymers in porous frameworks provides a unique platform for the development of high sensitive H 2 O 2 sensors.
Apart from the above mentioned, improving the concentration of proton carriers is a key factor to construct highly conductive and stable MOFs. The most effective strategy is to introduce the Lewis acid particles [101,102], molecules or counter ions [103,104] and the incorporation of proton-related substituents (-NH 2 , -SO 3 H, -COOH, -OH, -SH, etc.) in the ligands [105,106]. The increasing number of these guest molecules and proton carriers will form a hydrogen bonding network and enhance the conductivity [107,108]. Zhang [109] and coworkers bridged Cu 2+ with BIB and adp 2− to form a 2D propagation network with channel structure. The 2D layer channel structure was further connected by the hydrogenbond interactions, and then a 3D supramolecular architecture ([Cu(adp)(BIB)(H 2 O)] n ) was formed. [Cu(adp)(BIB)(H 2 O)] n performed a high reduction for H 2 O 2 with a low LOD (0.068 µM) and an excellent linear range (0.1 µM to 2.75 µM), which could be attributed to the electronic transport effect. Throughout the redox reaction, the channels and hydrogen-bond acted as transport corridors. Protons and electrons were transferred in an ordered manner. Consequently, the adsorption energy of the active sites for electrolytes and intermediates was decreased. Judging from the electron transfer, it was a two-step reaction. Firstly, [Cu(adp)(BIB)(H 2 O)] n reacts with OH − and then Cu 2+ is oxidized to Cu 3+ ; secondly, H 2 O 2 molecules react with Cu 3+ and then they are reduced to form O 2 due to the strong oxidizing from Cu 3+ .
Conductive electrical system consisted of metal ions and ligands with π-conjugate structure solve the serious poor conductivity issue for H 2 O 2 electrocatalysts; furthermore, the porous structure is conducive to promoting the mass transfer, and improving the catalytic rate of H 2 O 2 decomposition. Still, the high price of organic ligands remains a large obstruction on the pathway to large-scale commercialization.

Chemically Modified MOFs Based H 2 O 2 Sensor
Chemical modification is a feasible and effective way to introduce desired functions into MOFs materials. In general, MOFs can be functionally modified by their metal sites and/or organic linkers. For example, through the hybridization with conducting polymers, the electrical conductivity of the material can be improved [45,110].
Combining MOFs with conductive species can improve electronic conductivity, catalytic activity, and expand applications. The most common method is to combine the active component with carbon-based materials such as carbon nanotubes and ketone black carbon [111]. POMs (polyoxometalates), with internal unconventional molecular structure, stable physical/chemical properties and redox state, have shown superb activity in fabricating electrocatalysis. When they are used to prepare MOFs, the latest material POM-based MOFs (POMOFs) performed high specific surface and exposed more active sites [29,112,113]. However, the low conductivity reduces the catalytic activity of POMOFs as catalysts, resulting in low sensitivity and high detection limits when applied for H 2 O 2 detection. Wang et al. [58] developed POM-based MOF (NENU5 (polyoxometalate-based metal-organic framework)) grown in situ on KB by adopting a facile and feasible one-step solution method (Figure 4a). The low detection limit (1.03 µM) of NENU5-KB-3 for H 2 O 2 is mainly attributed to the high conductivity of KB and the high catalytic activity of NENU5. It also had a wide linear range from 10 µM to 50 mM and a high sensitivity of 33.77 µA mM −1 . More notably, the residual current decreased by~9% after continuous testing in 30 µM H 2 O 2 for 4 h. It indicated NENU5-KB-3 had good structural stability and stable catalytic activity. Furthermore, drug resistance results have revealed that the successive addition of 0.2 mM AA, 0.2 mM APAP, 0.2 mM DA and 0.2 mM glucose exerted no influence on H 2 O 2 detection, representing excellent stability and high selectivity.
Conductive substrates such as carbon cloth, FTO, ITO [112][113][114], etc. are also often used as supports for MOFs. They can improve the conductivity while exposing more active components, greatly improving the catalytic activity. Xia [56] and coworkers synthetized Co-MOF nanosheets array supported on Ti mesh (Co-MOF/TM). Co-MOF was synthesized by coordination of Co 2+ with terephthalic acid. With notable properties of large surface area, good stability, high porosity, and rich unsaturated Co 2+ sites, Co-MOF/TM exhibited outstanding catalytic performance with a low detection limit (0.25 µM). The catalytic activity can be attributed to the appearance of electronic defects on the surface of the nanosheets arising from the interaction between the Ti lattices and the Co-MOF. The sensor also showed good utility for monitoring the release of H 2 O 2 from A495 cells. Compared with most MOFs, Co-MOF had a lower cost in both raw materials and the preparation process.
The prospective availability of free space in MOFs permits another method of inducing conductivity, namely the introduction of guests (electron donors or acceptors). In some cases, they are complementary to the charge transfer of MOFs junctions or nodes. This approach not only enables the manufacture of conductive MOFs, but also allows their conductive properties to be modulated by specific stimuli without destroying their structure [95]. Hu et al. [57] assembled the petal-like nanonetwork structures by embedding the combination of pSC 4 -AuNPs and FeP on the surface of CuMOFs (Figure 4b). On the basis of maintaining the original catalytic activity, selective functionalization and well-defined configurations of CuMOFs, FeP (guest) and pSC 4 -AuNPs (body) were interlinked to form a nanonetwork structure for synergistic electron transfer to overcome the drawback of poor conductivity. The dual metallic active sites from the CuMOFs@FeP-pSC4-AuNPs increased the peroxidase activity, electrocatalytic activity and provided good thermal and storage stability. From which, it realized specific recognition of cancer cells by the signal output from the electronic transfer generated of H 2 O 2 decomposition, providing potential applications for clinical cancer detection (Figure 4c).
Transition metal elements are crucial components to build active adsorption sites in MOFs structures. Among them, Ni, Co and Fe show high activity in the kinetics of H 2 O 2 decomposition [53,115]. Ni ion has become an important non-precious metal ion for the detection of H 2 O 2 , and the substantial coordination number makes it easy to coordinate with organic ligands [116]. It is worth noting that the dispersion of unsaturated metal sites in MOFs plays an important role in the kinetic activity of H 2 O 2 decomposition [117]. Therefore, the introduction of another metal can produce more active sites to improve the electrochemical properties. In general, the synergistic interaction of two or more substances effectively improves electrocatalytic performance. This optimizes the electronic structure, reduces kinetic barriers and improves the charge transfer between the host metal atoms and the dopants during catalysis [118][119][120]. Li et al. [63] reported a new bimetals MOF (A(B)-Ni 1 Mo 0.5 -MOFs@AAC) by the liquid-phase and hydrothermal methods. Mo exhibited a strong hydrogen binding capacity and had a higher activity in the decomposition of H 2 O 2 [121]. What's more, the introduction of Ni-Mo bimetals enhanced the stability of the frameworks, and contributed to the catalytic performance ( Figure 4e). Therefore, the A(B)-Ni 1 Mo 0.5 -MOFs@AAC exhibited an outstanding detection performance for H 2 O 2 with a high sensitivity (0.277µA µM −1 ) and a noteworthy low detection limit of 0.185 µM. The establishment of bimetallic MOFs offers a new and simple idea for designing H 2 O 2 sensors with high structural stability and excellent catalytic activity.
Today, widely reported MOFs such as MIL (materials of institut lavoisier)-53(Fe), Fe-NH 2 -MIL-88, MIL-68(Fe), and MIL-100(Fe), etc. all exhibit salient H 2 O 2 decomposition properties. The narrow pore channels from the 3D block crystal structure restrict the diffusion rate of the substrate, and they further reduce the accessible active site in the 3D native crystal [46,122]. The special structure of 2D nanomaterials, such as large specific surface area, thin thickness and high surface volume, can expose more active sites on the surfaces, thus reducing the mass transfer resistance and diffusion potential barrier [123][124][125][126]. Wang et al. [127] synthesized a 2D bimetallic MOF nanosheets (2D Co-TCPP (tris (1-chloro-2-propyl) phosphate) (Fe)) with a thickness of less than 10 nm for the first time through a surface activity-assisted approach (Figure 4f). The highly exposed active sites enabled 2D Co-TCPP(Fe) to exhibit excellent H 2 O 2 catalytic decomposition activity with a detection limit of 0.15 × 10 −6 M. In addition, the sensor was successfully used for the real-time monitoring of H 2 O 2 secreted by living cells. The synthesis of 2D Co-TCPP(Fe) offers a versatile method for developing 2D bimetallic MOF nanosheets in high yields, which can be applied to a variety of areas.
through a surface activity-assisted approach (Figure 4f). The highly exposed active sites enabled 2D Co-TCPP(Fe) to exhibit excellent H2O2 catalytic decomposition activity with a detection limit of 0.15 × 10 −6 M. In addition, the sensor was successfully used for the real-time monitoring of H2O2 secreted by living cells. The synthesis of 2D Co-TCPP(Fe) offers a versatile method for developing 2D bimetallic MOF nanosheets in high yields, which can be applied to a variety of areas.

MOF Composites Based H 2 O 2 Sensor
Metal nanoparticles are a kind of economic, stable, simple to prepare nanomaterials, which have similar enzyme action to specific molecules [128,129]. In particular, "d" electron orbitals of precious metal nanomaterials are not filled, the surface may become easier to adsorb reactants. The moderate strength facilitates the formation of intermediate "active compounds" with high catalytic activity and excellent properties such as high temperature resistance, oxidation resistance and corrosion resistance [130,131]. Moreover, the active sites on their surface give them properties similar to those of biological enzymes [128,129]. Since MOFs have a permanent porous structure, the advantages of nanoparticles and MOFs can be utilized by introducing specific nanoparticles into MOFs to form a more stable material [132]. Shazia et al. [67] obtained a bimetallic MOF (Au-Pd@UiO-66-on-ZIF (zeolite imidazolium ester skeleton structure material) -L/CC) by introducing Au nanoparticles into Pd@UiO-66-on-ZIF-L/CC (Figure 5a). Electrochemical test results showed that the introduction of Au nanoparticles increased the adsorption sites of H 2 O 2 , and the synergistic effect between Au nanoparticles and Pd improved the catalytic performance (LOD was 21.2 nM), anti-interference, reproducibility, repeatability and stability of H 2 O 2 sensor. Meanwhile, real-time in situ detection of H 2 O 2 was achieved by culture of human adenocarcinoma alveolar basal epithelial cells (A549 cells) on Au-Pd@UiO-66-on-ZIF-L/CC, suggesting that the sensor has potential applications in cancer pathology (Figure 5b,c). Li et al. [62] prepared MNPs (magnetic nanoparticles) @Y-1, 4-NDC-MOF/ERGO (M = Ag, Cu) ternary composites by cation exchange strategy and electrochemical reduction. The embedding of metal nanomaterials improved the catalytic activity of the material, while the fast electron transfer effect of ERGO increased the electrical conductivity. What's more, the size tunability and selectivity (Figure 5d,e) of MOFs provided the material with high selectivity to H 2 O 2 . The material had potential applications in detecting the release of H 2 O 2 from cells. The interaction between the active component and the supporter plays a pivotal role in the catalytic reaction. On the one hand, uniform dispersion of metal nanoparticles can effectively increase the specific surface area while the unity of metal nanoparticles will minimize the specific surface area and surface energy, resulting in a severe loss of structural properties [131]. In order to increase the catalytic activity by loading more metallic nanoparticles, suitable carriers (crystals with high chemical stability, large specific surface area and high porosity) are preferably selected to disperse and immobilize metal particles [133,134]. Based on the large specific surface area, sufficient pore capacity and excellent crystallinity of MOF-67, Wang et al. [32] uniformly dispersed Au@Pt bimetallic nanoflowers on its surface. Compared with the single metal materials, Au@Pt with core-shell structure of bimetallic nanoflowers showed abundant active sites, good electrical conductivity, and better H 2 O 2 catalytic activity. The large specific surface area of the MOFs material provides more loading sites for more nanoparticles, thus further enhancing the catalytic effect. They have been proven to be a powerful electrochemical sensing platform with promising applications in biomedical monitoring and environmental analysis. In addition, some researchers have improved electrocatalytic performance by combining MOFs with 2D materials such as graphene or black phosphorus nanosheets to form novel composites. Cheng et al. [64] combined Mxene with MOFs to form a new 3D flower-like Cu-MOF/Mxene/GCE (glassy carbon electrode) material by taking advantage of Mxene's high electrical conductivity and large specific surface area (Figure 5f). Owing to the large specific surface area of MXene, Cu-MOF was evenly dispersed on the surface, and the metal sites of MXene and Cu-MOF improved the catalytic ability of H 2 O 2 . The electrochemical tests showed that Cu-MOF/Mxene/GCE had a wide linear range of 1 µM to 6.12 mM at −0.35V with a detection limit of 0.35 µM. The material was also used to measure H 2 O 2 in milk and serum with good recovery.

MOF Derivatives Based H2O2 Sensor
MOFs are often treated as self-sacrificing metal-organic precursors by post-treatment or high-temperature pyrolysis to construct well-defined heteroatom-doped carbonaceous microstructures with specific surface properties. A variety of typical 3D MOFs such as Prussian Blue, MOF-5, ZIF-67, and HKUST (Hong Kong uni-

MOF Derivatives Based H 2 O 2 Sensor
MOFs are often treated as self-sacrificing metal-organic precursors by post-treatment or high-temperature pyrolysis to construct well-defined heteroatom-doped carbonaceous microstructures with specific surface properties. A variety of typical 3D MOFs such as Prussian Blue, MOF-5, ZIF-67, and HKUST (Hong Kong university of science and technology, also called MOF-199)-1 are widely used as precursors or templates to build novel energy storage structures [135][136][137][138][139][140]. Furthermore, it has been reported that the carbon hybridization of transition metal oxides can not only improve the electrical conductivity of the catalyst, but also effectively prevent the aggregation of the catalyst. Therefore, transition metal oxides are often used as precursors for MOF derivatives [141][142][143]. Firstly, transition metal oxides are often used to provide active sites for enzyme-free detection and improve the activity of catalysts. Secondly, in situ formed CNT framework can improve the electronic conductivity, which is beneficial to the mass transfer of target molecules. Thirdly, the encapsulated carbon shell can effectively immobilize the oxidized nanoparticles, thereby inhibiting their aggregation. Qin's [144] group successfully pyrolyzed the MOFs and fabricated hollow frameworks of Co 3 O 4 /n-doped carbon nanotubes (Co 3 O 4 /NCNTs) in air. It indicated that Co 3 O 4 nanoparticles supplied active sites for the enzyme-free detection of H 2 O 2 , and the in situ formed carbon nanotube framework enhanced the electronic conductivity and accelerated the mass transfer of target molecules (Figure 6a). The encapsulated carbon shell could potently immobilize the oxidized nanoparticles, thus inhibiting their aggregation (Figure 6b). The established hollow frameworks exhibited excellent bifunctional detection capability with high sensitivity and low detection limitation for H 2 O 2 (87.40 µA (mmol/L) −1 cm −2 , 1 mmol/L) and glucose (5 mmol/L) (Figure 6c). This provides an effective idea for the establishment of non-enzymatic sensors with multifunctional detection for biological applications. In addition to the Co 3 O 4 /NCNTs hollow frameworks, Cui et al. [145] successfully synthesized hollow mesoporous CuCo 2 O 4 (meso-CuCo 2 O 4 ) microspheres and utilized them in both H 2 O 2 sensors and glucose biofuel cells (GFCs) for the first time (Figure 6d,e). Meanwhile, the nitrogen adsorption-desorption isotherm of meso-CuCo 2 O 4 was a type IV isotherm, confirming the existence of mesoporous structure and the intrinsic high specific surface area. On this basis, the inherently high catalytic activity of mesophase Cuco 2 o 4 exhibits high sensitivity and low detection limit (3 nM) for H 2 O 2 (Figure 6f). This further demonstrates that tunable porous structure can be constructed through MOFs template sacrificial method. Meanwhile, more metals active sites can be loaded with the increased surface area. It should be noted is that the calcination temperature needs to be preciously controlled, in order to prevent the potential issues of agglomeration and resulting reduced catalytic activity. versity of science and technology, also called MOF-199)-1 are widely used as precursors or templates to build novel energy storage structures [135][136][137][138][139][140]. Furthermore, it has been reported that the carbon hybridization of transition metal oxides can not only improve the electrical conductivity of the catalyst, but also effectively prevent the aggregation of the catalyst. Therefore, transition metal oxides are often used as precursors for MOF derivatives [141][142][143]. Firstly, transition metal oxides are often used to provide active sites for enzyme-free detection and improve the activity of catalysts. Secondly, in situ formed CNT framework can improve the electronic conductivity, which is beneficial to the mass transfer of target molecules. Thirdly, the encapsulated carbon shell can effectively immobilize the oxidized nanoparticles, thereby inhibiting their aggregation. Qin's [144] group successfully pyrolyzed the MOFs and fabricated hollow frameworks of Co3O4/n-doped carbon nanotubes (Co3O4/NCNTs) in air. It indicated that Co3O4 nanoparticles supplied active sites for the enzyme-free detection of H2O2, and the in situ formed carbon nanotube framework enhanced the electronic conductivity and accelerated the mass transfer of target molecules (Figure 6a). The encapsulated carbon shell could potently immobilize the oxidized nanoparticles, thus inhibiting their aggregation (Figure 6b). The established hollow frameworks exhibited excellent bifunctional detection capability with high sensitivity and low detection limitation for H2O2 (87.40 μA (mmol/L) −1 cm −2 , 1 mmol/L) and glucose (5 mmol/L) (Figure 6c). This provides an effective idea for the establishment of non-enzymatic sensors with multifunctional detection for biological applications. In addition to the Co3O4/NCNTs hollow frameworks, Cui et al. [145] successfully synthesized hollow mesoporous CuCo2O4 (meso-CuCo2O4) microspheres and utilized them in both H2O2 sensors and glucose biofuel cells (GFCs) for the first time (Figure 6d,e). Meanwhile, the nitrogen adsorption-desorption isotherm of meso-CuCo2O4 was a type IV isotherm, confirming the existence of mesoporous structure and the intrinsic high specific surface area. On this basis, the inherently high catalytic activity of mesophase Cuco2o4 exhibits high sensitivity and low detection limit (3 nM) for H2O2 (Figure 6f). This further demonstrates that tunable porous structure can be constructed through MOFs template sacrificial method. Meanwhile, more metals active sites can be loaded with the increased surface area. It should be noted is that the calcination temperature needs to be preciously controlled, in order to prevent the potential issues of agglomeration and resulting reduced catalytic activity.   [145]. Copyright 2018, Elsevier.

Conclusions and Outlook
In summary, we listed the advantages and disadvantages (such as conductivity, catalytic activity, stability, selectivity cost and environmental friendliness) of conducting MOFs, chemically modified MOFs, MOFs composites and MOF derivatives (Figure 7). We consider that the ideal electrochemical sensors for H 2 O 2 need to have the features of high conductivity, excellent catalytic activity, high selectivity, long-time stability, low cost, and environmental friendliness.
tration H2O2 [144]; Copyright 2020, Elsevier. (d) Nitrogen adsorption-desorption isotherm of meso-CuCo2O4. Insets, respectively, show the crystal structure and distribution of pore size of meso-CuCo2O4; (e) SEM image of meso-CuCo2O4; (f) Current-time curve of different H2O2 concentrations on CuCo2O4/CPE in 0.2 M NaOH electrolyte at +0.5 V. Insets a and b respectively were response time of addition H2O2 and current-time curve for a low concentration H2O2 [145]. Copyright 2018, Elsevier.

Conclusions and Outlook
In summary, we listed the advantages and disadvantages (such as conductivity, catalytic activity, stability, selectivity cost and environmental friendliness) of conducting MOFs, chemically modified MOFs, MOFs composites and MOF derivatives (Figure 7). We consider that the ideal electrochemical sensors for H2O2 need to have the features of high conductivity, excellent catalytic activity, high selectivity, long-time stability, low cost, and environmental friendliness. Figure 7. The pros and cons (such as detection limit, conductivity, stability, selectivity, low-cost and environmental-friendly) of the introduced catalysts for H2O2 electrochemical sensor (The outside is better, the inside is worse).
(i) Ultra-low detection limit In order to reduce the detection limit of the sensor, it will be crucial to improve the electrocatalytic activity of the catalyst. Correspondingly, the following strategies can be adopted to improve it: a. Constructing a hollow porous structure not only helps to increase the specific surface area to expose more active sites, but also gives more 3D electron transfer channels; b. Establishing a conductive network improves the conductivity of the catalyst and facilitates electron transfer; c. Composite strategy of coalescing conductive materials or materials with high activity for the decomposition of H2O2 enhances conductivity and catalytic activity.
(ii) Long-term stability It remains a huge challenge to achieve the long-term monitoring of H2O2 with sensors without any decrease in activity. In general, catalyzing over a long period of time can Figure 7. The pros and cons (such as detection limit, conductivity, stability, selectivity, low-cost and environmental-friendly) of the introduced catalysts for H 2 O 2 electrochemical sensor (The outside is better, the inside is worse).
(i) Ultra-low detection limit In order to reduce the detection limit of the sensor, it will be crucial to improve the electrocatalytic activity of the catalyst. Correspondingly, the following strategies can be adopted to improve it: a. Constructing a hollow porous structure not only helps to increase the specific surface area to expose more active sites, but also gives more 3D electron transfer channels; b. Establishing a conductive network improves the conductivity of the catalyst and facilitates electron transfer; c. Composite strategy of coalescing conductive materials or materials with high activity for the decomposition of H 2 O 2 enhances conductivity and catalytic activity.
(ii) Long-term stability It remains a huge challenge to achieve the long-term monitoring of H 2 O 2 with sensors without any decrease in activity. In general, catalyzing over a long period of time can lead to the structural changes of materials and deactivation of catalytic sites. To solve this problem, catalysts can be grown directly on highly corrosion-resistant conductive substrates (such as GR nanosheets, conductive glass, Ni foam, etc.) (iii) Large-scale production Large-scale production of cheap and efficient H 2 O 2 electrochemical sensors is of great significance for practical applications. However, the development process from basic research to commercialization is seriously hindered by the high price of some raw materials, synthesis processes and few synthesis methods. Therefore, new synthesis methods such as electrospinning, spray drying and Langmuir-Blodgett are needed to achieve precise control and mass production of electrocatalysts.
Overall, the development of highly sensitive and tolerant electrochemical sensors for H 2 O 2 is an important and challenging topic in the field of detection. Even in the near future biological enzymes are also currently the best choice for detecting H 2 O 2 , but this is beyond the scope of this review. We hope that this review can provide some meaningful inspirations for the design and fabrication of MOFs based H 2 O 2 electrochemical sensors. It is no doubt that the development of H 2 O 2 electrochemical sensors with comprehensive performance and low cost will make significant contributions and breakthroughs in biological, medical and other fields.