Novel route to size-controlled synthesis of MnFe₂O₄@MOF core-shell nanoparticles

Abstract

Nanoscale metal-organic framework (nMOF) is a distinctive type of crystalline compounds that consists of metal ions or clusters coordinated to organic ligands. This hybrid material has attracted fast-growing attention due to its tunable pore sizes, remarkably large surface areas, and high selectivity in uptaking small molecules. In this paper, we successfully developed a novel approach for synthesizing a core-shell structure with MIL-88B–4CH₃ as a tunable nMOF shell and MnFe₂O₄ as a magnetic core. We controlled the growth of the core-shell particles by introducing different acetic acid concentrations and with varied reaction time. Acetic acid works as a modulating agent that allows for nucleation rate control, leading to tailored particle size. Our results show an increase in the particle size with increasing acetic acid concentration or reaction time. This study provides a valuable methodology for synthesis of core-shell nanoparticles with controlled sizes based on nMOF platforms.

1. Introduction

Nanoscale metal–organic frameworks (nMOFs) represent a new generation of nanoporous materials that can easily self-assemble via the coordination of metal ions/clusters with organic linkers through strong coordination bonds [1]. Several studies have been conducted in the synthesis of nMOFs with controlled size and surface properties [2]. nMOFs exhibit excellent flexibility in controlling their porosity, surface charge, and hydrophobicity by using selected metal ions and/or different organic ligands, thus allowing prominent optimization [1]. This novel type of nanomaterial may be potentially utilized as an efficient drug carrier that has several advantages over other nanocarriers [3]. The advantages include high surface area (up to 7800 m² g⁻¹) and large pore volume (1–5 cm³ g⁻¹) that provides high loading efficiency of cargo [3,4]. These unique features also make nMOFs an attractive candidate for a wide range of applications in different fields owing to the ease of transporting guest molecules through their nanosized pores and the short diffusion pathways inside the nanocrystals. MOFs have been utilized for numerous purposes such as gas separation [5,6], chemical sensing [7,8], storage [9], and wastewater treatment [10,11]. In medicine, MOFs have been used to develop different targeted drug delivery systems by loading the drug cargo inside the pores of the particles and release within the targeted tumor. This leads to minimal side effects and increase drug concentrations at target sites [12–14]. nMOFs have also been utilized as imaging contrast agents by loading the MOFs with different dyes [15,16] or by covalent attachment of fluorescently labeled polymers [17]. Moreover, functionalization of the nMOFs with different antibodies allow using them as a biosensor [18].

Synthesis of porous core-shell particles has stimulated tremendous interest due to their versatile applications as a result of combining the features of the core and the shell materials. Different core-shell particles have been fabricated on the basis of zeolites, mesoporous oxides, polymers, and carbon materials [19–22]. However, they normally require long synthesis procedures and high incubation temperatures. These requirements render the fabrication process expensive and time consuming, which hinder large scale production. On the other hand, utilizing MOFs as a shell provides a good solution to these problems owing to their relatively simple fabrication steps, high porosity alongside with high surface area, and easily obtainable raw materials. Core-shell conjugates, with magnetic cores, show plentiful capabilities in diverse fields such as protein purification, metal toxin removal, magnetic resonance imaging, and controlled drug delivery systems [23]. In addition, encapsulating gold nanorods inside the MOFs enables their usage as contrast agents for X-ray, CT, and photoacoustic imaging (PAI) [24].

Different core-shell structures were previously reported that using metal oxide magnetic nanoparticles as a core and different nMOFs as their shells [25–31]. Most of the fabrication methods are based on “bottle-around-ship” method [32], in which the MOF precursors assemble around the pre-synthesized metal oxide magnetic nanoparticles such as Fe₃O₄@MIL-100(Fe) [25], Fe₃O₄@MIL-101(Fe) [27], and Fe₃O₄@MIL-101-SO₃ [29]. Another synthesis approach is to utilize partial transformation of preexisting MOF into γ-Fe₂O₃ to obtain a magnetic composite of MIL-53(Fe) or MIL-100(Fe) [33]. Since the targeted MOF in this study is MIL-88B which contains similar components as the MILs series of MOFs, we have successfully fabricated MnFe₂O₄@nMOF core-shell structure with rational adjustment of the synthetic condition. MnFe₂O₄ magnetic nanoparticles are selected as a core due their biocompatibility and high magnetic response compared with other ferrite nanoparticles including Fe₃O₄ [34–36]. MIL-88B–4CH₃ is selected as a shell as it shows great biocompatibility [37,38].

2. Experimental section

2.1. Chemicals

Manganese Iron Oxide Nanopowder (MnFe₂O₄, 99.99%, 28 nm) and Nanopowder dispersants for alcohol dispersion products were purchased from US Research Nanomaterials, Inc. Mercaptoacetic acid (MAA, HSCH₂COOH, ≥ 99%) was purchased from Sigma-Aldrich. N,N-Dimethylformamide (DMF, ACS reagent, 99.9%) and Acetic acid (CH₃COOH, ACS reagent, ≥99.7%) were obtained from Fisher Scientific. Iron(III) Chloride Hexahydrate (FeCl₃.6H₂O, 99+%) was purchased from Acros Organics. 2,3,5,6-tetramethylterephthalic acid (C₁₂H₁₄O₄) was obtained from Oakwood Chemical.

2.2. Functionalization of the MnFe₂O₄ core

Surface modification of MnFe₂O₄ is essential for the synthesis of the core-shell particles. The functionalization of MnFe₂O₄ nanospheres with MAA molecules produces carboxylate groups on the particle surface that allows MOF precursors to assemble around the modified MNP [25]. The functionalization stage plays a crucial role to initiate the step by step assembly because no core-shell composite could be synthesized using the unfunctionalized MNP [25]. MAA develops a better compatible interface between the MOF and the metal oxide core; moreover, it works as a binding agent that triggers the growth of MOF upon these surface-modified nanoparticles. The MAA-modified nanoparticles have been prepared according to the following process. In a typical procedure, 20 mg of MnFe₂O₄ was added to 4 mL of ethanol solution of mercaptoacetic acid (0.29 mM) under shaking for 24 h. The product was recovered by centrifugation at 14000 rpm for 10 min. The recovered particles were washed three times with a mixture of distilled water and ethanol (5:1), and were then re-dispersed in 5 mL DMF.

2.3. Synthesis of the nanocomposites MnFe₂O₄@MIL-88B–4CH₃

The synthesis of the proposed core-shell nanocomposites is based on hydrothermal method. The MOF precursors consists mainly of three major components which are metal iron, organic ligand, and organic solvent. Fe^III metal salt (30 mg) and tetramethylterephthalic acid organic linker (24 mg) were mixed with 36 mL DMF organic solvent and certain amount (X μL) of acetic acid as a modulation agent. The mixture was sonicated for 10 min. Then, 1 mL of the functionalized MNP solution was added to the mixture and sonicated for another 10 min. The solution was transferred to a parr bomb for crystallization in the oven for certain amount of time (T hours). The X (amount of acetic acid) and T (reaction time) were altered to control the size of the nanoconjugates. In order to investigate the effect of the X and T values on the nanocrystal size, the X and T values were tuned from 2 to 380 μL and from 2 to 12 h, respectively. At the end of the reaction time, the parr bomb was cooled under running water for 15 min. The dark solid product formed was recovered using centrifugation (15000 rpm, 15 min) and washed three times with 1:5 ethanol to water solution.

2.4. Characterization method

Scanning Electron microscopy (SEM) images were obtained using Hitachi S5500 device at an accelerating voltage of 20 kV. The samples for SEM measurement were prepared on silicon wafer substrates using an ethanol solution of the particles and left to dry for an hour. Transmission electron microscope (TEM) analyses were conducted with JEOL 2010F at 200 kV. Carbon-coated copper grids (200 mesh) was used as a substrate for TEM images. One drop of dispersed particles in an ethanol solution was deposited on the grid and the excess solvent was removed with a filter paper. The grid was then left to dry at room temperature for 2 h. The size distribution of the particles was obtained from the analysis of 20-50 particles in the SEM images using ImageJ 1.51J8 software. Powder X-ray diffraction (PXRD) patterns were collected by Rigaku Ultima IV Powder Diffractometer with 2θ range from 2 to 80° at scan rate of 0.02°/sec. Elemental analysis of carbon (C), iron (Fe) and, Manganese (Mn) for the samples was performed using Bruker Esprit 2.0 to ensure the presence of the Mn core in all samples.

3. Results and discussion

Different stages of the synthesis of MnFe₂O₄@MIL-88B–4CH₃ core-shell particles (i) with the presence of acetic acid in different concentrations at 12 h and 2 h reaction time, respectively, and (ii) with incubating at different time periods at 100 °C from 2-12 h, were explored to show the role of acetic acid concentration and the reaction time in the control of the particle size. Acetic acid was introduced as a modulating agent, and four different CH₃COOH/Fe³⁺ molar ratios (1.5, 2.3, 3.4 and 5.7) were tested at 12 h reaction time. The results show a significant increase of the synthesized particle size as the acetic acid concentration increases. These results are consistent with previous reports on controlling particle size by the introduction of modulating agents [39,40].

In a previous study [39], Tsuruoka et al. used a coordination modulation method to control the orientation of the MOF growth by changing the concentration of acetic acid during the synthesis process. They synthesized {Cu₂(ndc)₂(dabco)}n MOF which needs two different organic ligand 1,4-naphthalene dicarboxylate (ndc) and 1,4-diazabicyclo [2.2.2]octane (dabce). Each ligand is responsible for the growth of the particle in one direction. Acetic acid has the same functionality as the ndc ligand because they have the same carboxylate functionality. Therefore, acetic acid competes with the ndc ligand to coordinate with the metal ions and then suppresses the growth in one direction, thus leading to anisotropic MOF growth. This eventually allows formation of MOFs in different shapes from nanocubes to nanorods with the increase of acetic acid in the MOF precursor. In contrast, we changed both the reaction time and acetic acid concentrations for each sample in our studies. Our experimental results indicate that the reaction time plays an important role in controlling the particle size. Pham et al. used acetic acid as a deprotonating agent to control the particle size and the aspect ratio of the nanocrystals MIL-88B–NH₂ (Fe) [40]. Acetic acid allows the control of the nucleation rate of the MOF particles during the synthesis process through the control of the deprotonation of the carboxylic linkers, thus allowing for tailoring of the particle growth rate. In our study, we observed that increasing acetic acid concentrations results in the concomitant increase in the size of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particles. The particles are defect free with a highly crystalline framework and well-defined shape. During MOF growth in most of solvothermal reaction, the coordination groups of the organic ligand replace the solvent species and bind with metal ions. At the same time, the reverse reaction of ligand dissociation occurs [41]. Structural defects may occur in the forward reaction but the reverse reaction provides a possibility to reform the structure. However, if there is a very strong bonding between the metal ions and organic ligand, the reverse reaction cannot occur which results in unrepaired defects within the particle. Adding modulating agents, such as acetic acid, will stimulate the reverse reaction to occur, thus providing structural defect repair and generation of highly crystalline particles [42]. Using the synthesis method described in the method section, we have obtained nanoconjugate crystals ranging from nano to micro-sized particles by increasing of acetic acid concentrations (Fig. 1 (a–d)). Despite this significant increase of particle sizes from 157 nm to 1.33 μm, they still keep their morphological properties, a shape of bipyramidal hexagonal prism, unchanged. Perfect crystalline particles can be obtained at a high CH₃COOH/Fe³⁺ molar ratio (>3.4). Fig. 1 (e) shows the size dependence on varying acetic acid concentrations at 12 h crystallization time.

Fig. 1.

(a–d) SEM images of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particles with CH₃COOH/Fe³⁺ molar ratios of 1.5, 2.3, 3.4, and 5.7 under a reaction time of 12 h (Scale bar = 500 nm) (e) The size of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particle increases with increasing CH₃COOH/Fe³⁺ molar ratios. The reaction time for those experiments was at 12 h.

Furthermore, we investigated the effect of increasing CH₃COOH/Fe³⁺ molar ratios (0.4 to 36) on the particle sizes with the same reaction time of 2 h. Our experimental results show an increase of the core-shell particle sizes from 112 to 213 nm with increasing CH₃COOH/Fe³⁺ molar ratios from 2.3 to 3.4. This behavior is consistent with the corresponding one under 12 h reaction time. In contrast, no significant change in particle sizes has been observed with CH₃COOH/Fe³⁺ molar ratios below 2.3 (Fig. 2). On the other hand, only clusters rather than individual nanoparticles were formed for the samples with CH₃COOH/Fe³⁺ molar ratios over 3.4 (Fig. 3). We believe the main reason that no nanoparticles were formed may be attributed to the combination of a high acetic acid concentration and a short reaction time. Acetic acid slows down the crystal growth, therefore the core-shell particles will need more time to grow from small clusters to complete crystalline particles [39,40,42].

Fig. 2.

(a–e) SEM images of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particles with CH₃COOH/Fe³⁺ molar ratios of 0.4, 0.8, 1.5, 2.3, and 3.4 under a reaction time of 2 h (Scale bar = 400 nm) (f) The size of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particle remains similar for CH₃COOH/Fe³⁺ molar ratios below 2.3 and starts increasing over this value. The reaction time for those experiments was at 2 h.

Fig. 3.

(a–c) No particles are formed with CH₃COOH/Fe³⁺ molar ratios of 5.7, 9, and 36 under a reaction time of 2 h (Scale bar = 1 μm).

The crystallization time in the oven is a key factor in controlling the particle sizes. Generally, the longer crystallization time is, the thicker the shell is, and the larger the core-shell particle is. In this study, we explored the effect of adjusting the reaction time from 2 to 12 h with constant CH₃COOH/Fe³⁺ molar ratio of 2.3. We observed that the particle sizes increase with increasing reaction time in the oven up to 9 h (Fig. 4). Beyond 9 h of the reaction time, the particle sizes did not increase any further. The synthesis of MIL-88B–4CH₃ can be perceived as a chemical equilibrium to be established between the Fe³⁺ ions, carboxylate-terminated ligands and crystalline MOF.

$$\underset{\text{metal ion}}{{\text{Fe}}^{\text{3+}}}\text{+}\underset{\text{ligand}}{\text{HOOC}}\text{-L}\rightleftharpoons \underset{\text{crystalline MOF}}{\text{FeOOC-L}}{\text{+H}}^{\text{+}}$$

Fig. 4.

(a–d) SEM images of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particles under reaction time of 2, 6, 9, 12 h with the same CH₃COOH/Fe³⁺ molar ratio of 2.3. (Scale bar = 300 nm) (e) The size of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particle increases with increasing the reaction time. The CH₃COOH/Fe³⁺ molar ratio of those experiments was 2.3.

For reaction times below 9 h, the reaction has not achieved its equilibrium so that more Fe³⁺ ions and ligands will be converted to the crystalline MOF over time to further increase the nanoparticle size. As the equilibrium is established around 9 h, the concentrations of Fe³⁺ ions, organic ligands and the amount of crystalline MOF do not change any more. Additional reaction time will not generate more MOF based on the nature of a chemical equilibrium. The amount of MOF is thus determined by the concentrations of Fe³⁺ ions and ligands.

In order to confirm the formation of core-shell particles, we performed elemental analysis on all of the synthesized nanoparticles, especially looking for Manganese (Mn) element. The presence of Mn element in the synthesized nanoparticles proves the formation of the core-shell structure, as the magnetic core MnFe₂O₄ is the only source of Mn element. We analyzed the three main elements: iron, carbon, and manganese. The results show weight percentages of Mn element ranging from 11-29%, thus confirming the presence of the magnetic core in all the core-shell nanoparticles. We reported the particle sizes based on analyzing 20–50 particles in the SEM images for each sample using ImageJ software.

For further investigations of the core-shell nanoparticles, we selected the core-shell particles with the smallest size (CH3COOH/Fe³⁺ molar ratio = 2.3) for more characterization by imaging with TEM and performing PXRD. TEM image of the nanoparticle in Fig. 5(a) shows a core-shell structure. The MOF shell has a thickness of approximately 40 nm. The results from PXRD measurements of the MnFe₂O₄, MIL-88B–4CH₃, and MnFe₂O₄@MIL-88B–4CH₃ nanoparticles are shown in Fig. 5(b). It is clear that the diffraction peaks of the MnFe₂O₄@MIL-88B–4CH₃ core-shell nanoparticles contain the peaks from both MnFe₂O₄ magnetic core and MIL-88B-4CH₃ shell. This result has further confirmed the core-shell structure of MnFe₂O₄@MIL-88B–4CH3 nanoparticles.

Fig. 5.

(a) TEM image of the MnFe₂O₄@MIL-88B–4CH₃ core-shell particle with CH3COOH/Fe³⁺ molar ratio equals to 2.3. (Scale bar = 100 nm). (b) PXRD for the MnFe₂O₄ magnetic nanoparticles, Bare MIL-88B–4CH₃ MOF, and MnFe₂O₄@MIL-88B–4CH₃ core-shell nanoparticles.

4. Conclusion

This study reports the fabrication of core-shell nanoparticles based on MnFe₂O₄ as a magnetic core and MIL-88B–4CH₃ as a shell. Acetic acid concentrations and reaction times were explored to show their effects on controlling the growth of the particles and thus tailoring their sizes. As acetic acid is a modulating agent that controls the nucleation rate of the particles, it leads to the synthesis of larger and well-defined crystalline nanoparticles by increasing the concentration of acetic acid in the sample precursor. There is however an upper limit of the acetic acid concentration that can be used. Additionally, the reaction time can be utilized to control the particle sizes. With longer reaction times there was an observed increase in nMOF shell thickness. We expect that the core-shell nanoparticles with well-controlled sizes will have potential applications in several fields, such as for toxins removal, magnetic resonance imaging, and drug delivery systems.