Review—Metal Organic Framework Based Nanomaterials for Electrochemical Sensing of Toxic Heavy Metal Ions: Progress and Their Prospects

Mercury, a toxic and poisonous heavy metal which exists in all three forms such as elemental, inorganic salt and organic compound. ^53,54 However, the most deadly form of mercury is methylmercury, which affected the peoples from Iraq and Japan (minmata disease) by intake of mercury poisoned foods. ^55–59 The toxic effects caused by mercury will induce serious threat to the living organisms which makes concern to detect the trace levels of mercury using electrochemical method. Recent studies have been witnessed that MOF can be employed as an active nanomaterial substrate for the exclusion of heavy metal ions, because of its excellent binding ability ⁶⁰ have fabricated zincophosphite framework (NTOU4) nanoparticle surface coated with in-situ electrodeposition of conducting polyaniline (PANI) for electrochemical sensing of Hg²⁺. The synthesized NTOU4 framework is highly chemical stable which can be further used for deposition of conducting polymers on the surface to improve its conductivity. Interestingly, the in-situ electrodeposition of PANI provides uniform film coating and thickness over the surface of NTOU4 and therefore it enhances the conductivity and sensing behaviour of the modified electrode. The NTOU4 nano-PANI modified electrode for the evaluation of mercury ions were examined by differential pulse voltammetry (DPV). The DPV curves exhibited a linear response for each addition of mercury within the concentration range from 0.05 to 27.5 nM. The sensitivity and detection limit was calculated to be 29.79 μA nM⁻¹ cm⁻² and 34.9 pM, respectively. The NTOU4 nano-PANI have demonstrated a good selectivity for the signal response towards Hg²⁺, whereas the other metal ions such as Cr³⁺, Co²⁺, Mg²⁺, Cu²⁺, Pb²⁺, Cd²⁺, and As³⁺ shows least response in comparison with Hg^2+. Moreover, the hybrid electrode showed a reasonable practical applicability which can detect 5 nM of Hg²⁺ ions in river water and also even at high salt content of sea water samples.

The major drawback arises using MOF modified electrode is the leaching of fabricated materials from the electrode surface which resulted in poor stability. It has proposed that a free-standing electrode to grow methanethiol functionalized Zr-2,5-dimercaptoterephthalic acid based MOF (Zr-DMBD) on 3D macroporous carbon. ⁶¹ Hence, the uniformly decorated MOF nanoarray provides a large surface area with 3D macropores which facilitates the rapid determination of Hg²⁺ ions. Under optimized pH conditions at 0.2 M HAc-NaAc buffer (pH − 6.0), Zr-DMBD MOFs showed a drastic response for the addition of 2 μM mercury, and the electrochemical response at the modified electrode is found to be six times higher than 3D kenaf stem-derived carbon. The observed high response is due to the assembly of 3D porous architecture with massive number of Zr-DMBD MOFs on modified electrode which are uniformly decorated on carbon support that provides mass transport of Hg ions at the interface. The sensing performance of mercury ions was investigated by using square wave voltammetry technique. The detection of mercury was found to be in linear relationship from 0.25 μM to 3.5 μM, with a sensitivity of 324.58 μA μM⁻¹ cm⁻². The limit of detection (LOD) was obtained as 0.05 μM. In addition, the Zr-DMBD MOFs exhibited excellent anti-interference for Hg (II) ion, even at fivefold increase in concentration of various metal ion like Cu(II), Cd(II), Pb(II), Ni(II) and Zn(II). However, the other metal ions showed lesser interference effect, which reveals that Zr-DMBD MOFs is highly selective for the determination of mercury ions. The reusability of the modified electrode towards Hg²⁺ was performed with Zr-DMBD MOF, and it does not show any significant change in the response for four continuous cycles reveals good repeatability

It is a well-known fact that the MOF comprised to form a 3D metal organic framework with inorganic centre metal ion and ligands as nodes and linkers, respectively. However, the performance of the MOF towards the detection of mercury ions is predominantly dependent on the appropriate selection of metal species as nodes. In this regard, Cu (II) MOF is considered to be an alternative to other Zr(II) and Fe(III) based MOFs, because of its cost-effective, high chemical stability and excellent detection ability for the adsorption of mercury ions. The developed Cu²⁺ based MOF using 1,3,5-benzenetricarboxylic acid as linker, in the presence of Cu²⁺ is responsible for signal amplification and the linker provides enhancement in the stability. ⁶² Benefiting from the strong coordination between Hg²⁺ ion and thymine-rich DNA strands, and the sensing substrate was constructed using synthesized Cu(II) MOF by linking with T-rich DNA strands, because it is highly specific for the recognition of mercury ions to form a stable coordination linking of T-Hg²⁺-T unit. The resultant coordination unit is found to be stable than Watson-Crick derived adenine-thymine base pairs (A-T). Under optimized conditions, the DPV response at Cu-MOFs/GCE showed a linear response between difference in current (ΔI) and the log of [Hg²⁺] in the range from 10 fM to 0.1 μM. The limit of determination for Hg²⁺ is found to be 4.8 fM. In comparison with other MOFs, Cu-MOFs/GCE showed a lower detection limit which signifies the strong binding ability of Hg²⁺ ions. To evaluate the presence of possible interfering species in dairy product such as Ca²⁺, Mg²⁺, Zn²⁺, Cd²⁺, Pb²⁺, Fe²⁺, Co²⁺ and Mn²⁺ ions were added into Hg²⁺. It has been observed that, after addition of other interfering metal ion has shown negligible change in the current response of Hg²⁺ in dairy product, which reveals that Cu(II) MOF linked with T-rich DNA strands possess high selectivity and strong binding ability to form T-Hg²⁺-T strong coordination linkage. When evaluating the sensing performance of Hg²⁺ in milk samples, the Cu(II) MOF showed negligible significant influence of Hg²⁺ even in the presence of protein, fat and other microorganisms present in the milk have confirmed the high selectivity of the proposed sensor. The repeatability of Cu-MOF was carried out in 100 nM mercury ion showed 97.8% of its original response indicates satisfactory reversibility of the proposed sensor towards Hg²⁺.

To establish ultrasensitive detection of mercury at attomolar levels, the development of high conductive sensing interface for signal amplification is highly desired. It can be seen that a designed sensing interface were comprised of porous GO@Au hybrids which offers high porosity, good electrical conductivity, biocompatibility and large surface area that can enhance the sensitivity for the detection of mercury. ⁶³ For enzyme free amplification of sensing signal, Cu(II) MOF is considered as a promising catalyst carriers for T-rich DNA sensing of mercury. Taking into consideration of above facts, a sensing platform is comprised of porous GO@Au and Cu(II)-anchored MOFs which can acts as a conducting interface and enzyme-free signal amplification, respectively, and thus thyamine-rich DNA sensor is acheived to detect Hg²⁺ in dairy products. Furthermore, the proposed sensor is subjected to determine mercury at different concentration levels ranging from 0.001 aM to 10 μM. The DPV current response is found to be linear between ΔI and log [Hg²⁺] from 0.10 aM to 100 nM with a detection limit was found to be 0.001 aM. The ultrasensitive detection at attamolar levels is ascribed to high conducting porous GO@Au at the interface which enhances electrical conductivity and thus resulted to a larger signal amplification by Cu(II) MOF. The repetability of the proposed sensor was evaluated using porous GO@Au and Cu(II)-anchored MOFs in presence of 10 nM Hg²⁺ and it was found to be 2.6%, indicates good reversibility.

The possible mechanism can be explained as follows: The reaction mechanism involves two step process 1.accumulation step and followed by 2. Anodic stripping of adsorbed metal ions from the electrode surface. ¹⁵ Firstly, the heavy metal ions like (Hg²⁺, Pb²⁺, As³⁺ or Cd²⁺) were spiked into the buffer solution and allowed to accumulate on the electrode surface for few seconds. During this process, the heavy metal ions were coordinated with MOF on the electrode surface through chelation and bonding. In the next step, when applying the electrode potential, the adsorbed metal ions were reduced first and stripping from the electrode surface. The stripping peak intensity reflects the concentration of metal ions in the solution (Fig. 3).

If the DNA molecules were immobilized on the electrode surface, after spiking of heavy metal ions like (Hg²⁺, Pb²⁺, As³⁺ or Cd²⁺) a strong coordination between Hg²⁺ ion and thymine-rich DNA strands will occur. The T-rich DNA strands are highly specific for the recognition of mercury ions to form a stable coordination linking of T-Hg²⁺-T unit. The resultant coordination unit is found to be stable than Watson-Crick derived adenine-thymine base pairs (A-T). ⁶²

Lead (Pb) a natural abundant element in soil, however its presence at lower concentration can be recognized as an environmental contamination, when it accumulates over time in human body which leads to mental and physical impairment. ^64,65 The toxicity of lead is more harmful to young children affecting their multiple body systems like brain and nervous system. The release of lead from bone into blood during pregnancy may cause lead toxicity for the developing fetus. ^66–71 Therefore, developing electrochemical strategies for detection of lead in environmental samples like water is a huge demand. The trace level of estimation of lead in water can be fulfilled by utilization of MOF based materials as electrode substrate to achieve high selectivity and ultra-low detection limits.

In the synthesized Zn₄O(BDC)₃ based MOF-5, Zn₄O can acts as a metal cluster and 1,4-benzenedicarboxylate (BDC) as conjugate ligand which will combine to form a cubic cell with rigid framework containing two different pores. ⁷² MOF-5 has unique benefits of chemical stability, high porosity, 3D porous structure makes them as promising modifier in developing carbon paste electrode. Therefore, Wang and co-workers have demonstrated carbon paste electrode using MOF-5 for the detection of lead. Carbon powder was mixed with MOF-5 in few drops of ethanol, after evaporation the fine powder was mixed with mineral oil and transferred to a mortar, to form a carbon-MOF-5 paste. The paste was filled in a glass tube and connected with copper wire, to obtain MOF based carbon paste electrode. The DPV measurements were carried out with different concentrations of lead in 0.1 M acetate buffer of pH 5. Upon addition of lead concentration from 1.0 × 10⁻⁸ to 1.0 × 10⁻⁶ M, the DPV peak observed at -0.45 V and shifted to lower potentials which may be due to the specific interactions between the composition of the materials at the electrode surface and the thin layer of Pb deposited onto the electrode. More reliable results were observed for analyzing the environmental lake and tap water samples in quantification of lead. The modified electrode was subjected to 11 repetitive analysis with carbon-MOF-5 in presence of 0.1 μM of Pb²⁺, a relative standard deviation (RSD) was found to be 3.4 %. These results indicate good reusability of the modified electrode for lead sensor.

By the same way, the demonstration of amino functionalized Ni-MOF for the detection of Pb²⁺ has been reported. ⁷³ Ni-MOF was synthesized using 2-aminobenzenedicarboxylic acid by one pot hydrothermal method. The electrochemical sensor was constructed using synthesized Ni- MOF modified over GCE surface and can be utilized for detection of Pb²⁺ ions. For better detection of lead, the parameters like pH, deposition time and potential were optimized for estimation at microgram levels. The optimized experimental conditions like acetate buffer (pH-5.8), deposition time of 330s and deposition potential at −0.9 V, quantitative SQV analyses was carried out at various concentrations of Pb²⁺. During each addition of Pb²⁺ concentration from 0.5 μM to 6.0 μM, the SQV response showed oxidation peak without any change/shift in its potential, with the observation of linear relationship between concentration of lead and stripping anodic current. When subjected to investigate the effect of interference species like Cr³⁺, Cu²⁺ and Cd²⁺, the addition of 1 μM into the NaAc–HAc-buffered solution does not show any change in the response towards Pb, this behavior indicates that Ni-MOF/GCE is highly selective for the estimation of Pb at inclusion of other metal ions.

To detect Pb²⁺ in nanomolar levels using MOF, DNAzyme (GR-5) functionalized iron-porphyrinic (DNA/Fe-MOF) for effective monitoring of Pb²⁺ was developed. ² Here-in, the DNAzyme possess high stability and it can remain its binding activity for Pb²⁺ even after repeated denaturation. Whereas, iron-porphyrinic -MOF acts as an enzyme mimic to produce more effective signal amplification, and therefore it provides additional opportunity to enhance sensitivity of Pb²⁺. Taking into advantageous, he has also designed DNA/Fe-MOF probe to recognize specific detection of Pb and also to amplify current signal during measurement at low concentration of Pb²⁺ ions. The electrode fabrication was carried out as follows: Pb²⁺ and DNA/Fe-MOF probe were dissolved in Tris-acetate: NaCl buffer, pH 7.0 in a ratio of 1:9. An aliquot of the above mixture was drop-casted on the synthetic oligonucleotides modified surface. After continuous washing the modified electrode with Tris-acetate buffer, chronoamperometric measurements were carried out at +0.1 V for further detection of Pb²⁺. The DNA/Fe-MOF probe modified electrode was placed in 0.1 M acetate buffer, pH 5.5 containing TMB and hydrogen peroxide, with increasing Pb²⁺ concentration recorded at +0.1 V. The chronoamperometric current response displayed linear response between current and log[Pb²⁺] from 0.05 to 200 nM is obtained with a low detection limit of 0.034 nM. The modified electrode showed good selectivity towards Pb²⁺, even in presence of Ca²⁺, Hg²⁺, Cu²⁺, Fe³⁺, Co²⁺, Zn²⁺, Ni²⁺ and Ag⁺. Also, the electrochemical response for Pb²⁺ in environmental samples exhibited the recovery value of 95 % to 104%, revealed good accuracy for real-time analysis (Fig. 4).

An extended work was done by ³ with Pd-Pt modified Fe-MIL-88 MOF for sensitive detection of Pb²⁺ in picomolar levels with an earlier report. ² The newly designed 8–17 DNAzyme is composed of 8–17 deoxynucleotides which is highly selective to Pb²⁺, which cleaves into two pieces of strands after electrocatalytic activity. Therefore after the addition of Pb²⁺, the DNAzyme is cleaved by Pb²⁺, resulting in strand detachment. The repeatability of the proposed sensor was demonstrate in 1 μM Pb²⁺, shows a RSD of about 3.27%, shows good reversibility towards detection of Pb²⁺ ions.

Arsenic (As) is a naturally available element found in the ground water over globally. ^74–77 Especially, in the North of Chile, population growth, intensive agriculture and mining, are probably the most important aspects that make water a vital element of its integral development. The main problem found in the north of Chile is the presence of Arsenic as harmful contaminants present in water and soil with maximum contaminant level of 10 μg l⁻¹. ^78,79 Its inorganic form is extremely toxic and its presence is predominantly associated with altiplanic quaternary volcanism. It is also reported that, the natural water contains both As³⁺ and As⁵⁺, therefore electrochemical determination of As in water samples is highly desirable. Taking into beneficiary of electrochemical detection method, MOF is a good choice of electrode material with high surface area, porosity which can capture the As³⁺ ions in polluted water.

Fe(III)-based MOF and mesoporous Fe₃O₄@C nanocapsules are reported. ⁴ Initially mFe₃O₄@C nanocapsules were prepared using solvothermal method by mixing of SiO₂ nanoparticles with ferrocene, followed by etching with ammonia resulted into a core–shell structure. The prepared mFe₃O₄@C was further reacted with 2-amino-terephthalic acid and FeCl₃·6H₂O using hydrothermal reaction at 120 °C to obtain Fe-MOF@mFe₃O₄@mC nanocomposite. The resultant mesoporous MOF based nanocomposite possesses high surface area, good dispersion ability and good electrochemical performance. As previously discussed, DNA functionalized iron-porphyrinic were used as a signal probe for the determination of Pb²⁺. Taking into advantages of hydrogen-bonding and supramolecular stacking, the immobilization of aptamer strands over Fe-MOF@mFe₃O₄@mC nanocomposite for determination of As³⁺ was adopted. In addition, Fe-MOF/Fe3O4/mC nanocomposite DPV measurements were carried out and electrochemical efficiency was investigated by measuring different concentrations of As3+, ranging from 0.01 to 10.0 nM, with a detection limit of 6.73 pM. The selective estimation of Arsenic ions was examined using Fe-MOF/Fe3O4/mC nanocomposite in presence of other metal ions like Ag⁺, Zn²⁺, Ca²⁺ and Mn²⁺. It has been observed that even in presence of other metal ions, the electrochemical response towards As3+ remains unaltered signifies that the proposed modified electrode is highly selective towards arsenic detection. For the detection of arsenic, the nanocomposite electrode exhibited good selectivity and appropriate reproducibility of about 4.66 % (Fig. 5).

To enhance the signal amplification of MOF with conducting platform over the electrode surface, the development of non-biosensor assay based graphene oxide/Zn-MOF was fabricated with GCE for the detection of As³⁺. ⁸⁰ The single step synthesis of GO/Zn-MOF was carried out by dissolving ZnCl₂ and C₅H₉N₃ 2HCl in warm methanol (20 ml) and then GO was added into the above mixture and subjected to sonication for 20 min. The reactant mixture was then moved into an autoclave of stainless steel and heated for 48 h at 95 °C. In addition, 1.5 mg ml⁻¹ of graphene oxide/Zn-MOF dispersed in water was dropped at the surface of the GCE and cyclic voltammetry was carried out to obtain a stable voltammogram without any difference between consecutive cycles by sweeping the potential range from −1.0 to 0.6 V. Under optimized experimental conditions like supporting electrolyte, pH, of nanocomposite on GCE, accumulation potential and time, anodic stripping voltammetry was examined for determination of As³⁺ at different concentrations. A good linearity was obtained between the anodic current and the concentration of As³⁺ within the range from 0.2 to 25 ppb, with a low detection limit of 0.06 ppb based on 3σ/m method. To estimate the selective detection of arsenic using Gr/Zn-MOF by adding high concentration of 50 ppb of Hg²⁺, Zn²⁺, Fe²⁺, Bi³⁺, Cr³⁺ and Pb²⁺ containing 10 ppb of As3+ doesnot show any significant response for interfering metal ions, reflects that modified electrode is highly selective for arsenic determination. Furthermore, the modified electrode exhibited superior reproducibility of about 2.1% when subjected to analysis at 8 ppb As concentration.

For the electrochemical determination of As³⁺, various types of nanomaterials such as carbon materials, metal and metal oxide nanoparticles have been widely used. Among them highly stable noble gold (Au) is highly selective for arsenic oxidation. Despite the high conductivity of Au, In order to increase electrocatalytic activity, it is extremely important to increase the active sites, which could able to estimate arsenic presence in water sources even at ultra-trace levels. Therefore, a demonstration of Fe-MOF based plasmonic Ag/Au HPNSs@FO as ultramicroelectrode for sensitive determination of arsenic has reported. ⁸¹ Hence, integrating the advantages of plasmonic nanoparticles and porous Fe-MOF will enhance the good adsorption of As(III), resulted in ultra-sensitive detection of arsenic. The electrocatalytic activity towards arsenic sensing at plasmonic Ag/Au HPNSs@FO is performed using DPV. With increasing concentration of arsenic from 0.05 to 16 ppb, the anodic peak current increases linearly with increasing concentration of As³⁺, without any shift in the anodic peak potential at 0.065 V. The ultra-microelectrode showed a ultra-low limit of detection of 0.01 ppb, the calculated LOD value is lower than the permitted concentration levels of arsenic in drinking water by WHO.

Cadmium (Cd), also a highly toxic element and recognized as human carcinogen. The presence of Cd in the crust of the earth was found to be poor in quantity, but due to the modern industrialization the levels were increased rapidly and become human threat to the environment. ^82,83 The exposure of Cd at low concentration levels is highly toxic which causes renal dysfunction to the kidneys. ^84–88 Few reports are available for the determination of Cd using electrochemical detection of Cd in water using MOF as electrode material. The major findings of these research reports are discussed as follows:

Bi(III)-impregnated MIL-101(Cr-MOF) is deposited on the carbon cloth for effective determination of Cd²⁺. ⁸⁹ The impregnation of Bi into Cr-MOF was carried out by dissolving bismuth nitrate and MIL-101 dispersed in nitric acid solution (pH-4) for 6 h. The resultant product was washed, centrifuged and dried in an vacuum at 323 K. 1 mg of Bi^III/MIL-101(Cr-MOF) was dispersed in DMF and dropcasted on carbon cloth and then dried at 323 K to obtain Bi/MIL-101(Cr-MOF)/CC. The optimum pH of 5.0, accumulation time and deposition potential of 600 s and −1.2 V was chosen. With an increased Cd concentration, DPV was recorded from 0.1 to 30 μg l⁻¹ with a measured detection limit of 3 μg l⁻¹. Bi/MIL101(Cr)/CCE showed an excellent anti-interference and reproducibility of about 1.7% in presence of 50 μM Cd²⁺ concentration. Satisfactory recoveries have been recorded for the determination of Cd(II) from water samples. The selectivity performance of the modified electrode for Cd²⁺ ion was evaluated using DPV in presence of 1000 fold excess of Ca²⁺, Mg²⁺, Fe²⁺, Zn²⁺ and Ni²⁺ containing 10 μM Cd²⁺. It was found that the stripping response did not show any significant change at 50 and 100 fold increase in interference metal ions but it reduced to ∼23% after adding 1000 fold increase of those interference species. These results indicate that Bi/MIL-Cr/CCE showed good selectivity towards cadmium detection.

To further enhance the conductivity of MOF and also to determine Cd concentration at ultra-trace levels, the demonstration of UiO-66-NH₂@PANI by loading PANI onto MOF surface was reported. ⁹⁰ Here, PANI can increase the conductivity efficiently and speed up the diffusion of the electron/ion in the composite matrix. The synthesis of UiO-66-NH2@PANI were involved with a two-step process: 1. Synthesis of UiO-66-NH₂ was carried out by mixing ZrCl₄ and 2-NH₂-benzenedicarboxylate in 50 ml DMF by ultrasonic vibration for 30 min and kept in an autoclave at 120 °C for 48 h. 2. Further, the obtained UiO-66-NH₂ was dispersed in HCl followed by the addition of aniline and APS which undergoes self-polymerization to obtain PANI loaded on the UiO-66-NH2 matrix. Deposition potential at −1.2 V, accumulation time of 120 s, by selecting an ideal pH of 5.0, a linear relationship between current and Cd concentration within the range of 0.5 to 600 mg l⁻¹ was shown by the DPV response, and the detection limit was found to be 0.3 mg l⁻¹. By evaluating the cadmium ions for repeatability analysis, the functional applicability of the proposed sensor showed 3.9% when subjected to 6 repetitive measurements. The conductive polymer (PANI) loaded on UiO-66-NH₂ will lead to intriguing discoveries in MOF-based electrochemical sensing of toxic metal ions. The sources and the toxicity effect of various heavy metals like mercury, lead, arsenic and cadmium can be compared with various MOF-based modified electrodes as represented in Table I.

Even though there are numerous advantages on using MOF such as

• Excellent structural properties
• Large surface area
• High resistance toward many chemicals
• Retains full crystallinity and structural stability in aqueous medium

There are few critical limitations too:

• Poor conductivity of MOF and MOFzyme
• Co-accumulation of other metal species along with the target ion.