A simple and versatile solvothermal configuration to synthesize superparamagnetic iron oxide nanoparticles using a coaxial microwave antenna

Abstract

Magnetic iron oxide nanoparticles (IONs) with controllable physicochemical and magnetic properties were synthesized by a fast and simple solvothermal microwave (MW) assisted approach. The MW-assisted synthesis using a coaxial microwave antenna was carried out in different routes: (i) a fast one-step solvothermal approach, and (ii) a non-aqueous sol–gel system. This innovative configuration obtained IONs maghemite crystal phase, in a very short reaction time (from 5 to 15 min), with a small size (6 nm) and narrow particle size distribution. Magnetization as a function of the applied magnetic field revealed that all the samples showed superparamagnetisms, with a saturation magnetization ranging from 60 to 68 emu g⁻¹ (T = 300 K). TEM, XRD, FTIR, TG, and magnetic measurements were used to fully characterize the IONs. Not only did the proposed methodologies using the coaxial MW configuration produce IONs with similar or improved physicochemical and magnetic properties, but they also overcame the classical drawbacks of oven-type MW configurations.

---

Introduction

Iron oxide nanoparticles (IONs) and their particular crystal phases, namely magnetite (Fe₃O₄), hematite (α-Fe₂O₃) and maghemite (γ-Fe₂O₃), are very attractive materials due to their magnetic properties.¹

IONs have been intensively studied in a broad range of disciplines and fields. They play a key role in many technological applications such as magnetic storage media,^2–4 catalysts,^5,6 and sensors.⁷

Magnetic IONs have also been widely used in biomedical research and bio-applications since they have many other advantages over other metallic nanoparticles, such as biocompatibility, low cost, chemical and physical stability, and environmentally friendly properties.¹ IONs have been used in magnetic resonance imaging to provide enhanced contrast at very low concentrations (nanomolar range) for studying tumors,^8–12 as a targeted delivery vehicle and as a drug delivery coating for nanoscale anti-cancer drugs,^13,14 as well as applications in cancer therapy as a potential mediator for magnetic hyperthermia.^15–17

The chemical composition, morphology, and size of IONs are crucial in determining their successful application since their magnetic properties are strongly related to these parameters. For example, regarding the chemical composition, namely the saturation magnetization (M_s) at room temperature, are different in terms of the three main crystal phases of iron oxide: hematite has a weak ferromagnetism (M_s ≤ 1 emu g⁻¹), while maghemite and magnetite exhibit high ferrimagnetism (M_s = 92 emu g⁻¹).¹ On the other hand, IONs usually show superparamagnetic behavior (at room temperature) when their particle size is below 15 nm.¹⁸ The magnetic properties are also influenced by the morphology of the Fe₃O₄,¹⁹ while the iron salt precursor is related to the crystal phase obtained.²⁰ Therefore, the precise control of the crystallinity, morphology, and particle size is very important in order to successfully obtain magnetic IONs with desirable properties.^21–23

These characteristics also depend on the methodology used to synthesize them. Co-precipitation is a simple and popular route to synthesize IONs. The method is based on the co-precipitation of ferrous and ferric salts in an alkaline or acidic aqueous medium.^24,25 Many other methodologies have been proposed to synthesize IONs, such as the thermal decomposition of the iron organic complex precursors,²⁶ thermolysis,²⁷ sonochemical methods,²⁸ microemulsion,²⁹ and the hydrothermal/solvothermal approach.^30–32

Over the last few years, special attention has focused on the microwave-assisted route, which is generally faster, eco-friendly and very energy efficient, compared with the classical conventional thermal activation used in the alternative routes mentioned above.

The microwave-assisted IONs synthesis approaches including the hydrothermal synthesis,^33,34 the non-hydrolytic sol–gel route,^35–38 the polyol approach,^7,39,40 and the solvothermal synthesis.^41,42

In spite of the advantages of using microwaves to assist the hydrothermal approach, these methodologies use microwave oven-type devices. These reactors have several drawbacks, such as a difficult industrial scale-up, a low penetration depth of MW at 2.45 GHz (a few centimeters in a medium with high dielectric losses like water), and a non-uniform distribution of the electromagnetic fields.

As an alternative, the coaxial microwave technology (which makes use of a coaxial dipole antenna to apply the electromagnetic energy inside the reacting medium) is highly flexible, easily controllable and has a versatile scale-up since different reactor geometries are possible rather than the conventional close-device microwave oven reactors.⁴³ Moreover, the industrial scale-up is simpler, since there are not dimensional constraints and a wide range of materials is eligible (Teflon, quartz, glass, plastic and so on). This configuration has been successfully used in several applications such as heterogeneous catalytic processes,⁴⁴ green solid–liquid extractions,^45,46 and mesoporous material syntheses.⁴⁷

This paper thus describes a versatile configuration using the coaxial microwave technology as a simple alternative to synthesize IONs with controllable physicochemical and magnetic properties. The microwave-assisted synthesis using a coaxial microwave antenna is explored in different routes: (i) a fast one-step hydrothermal co-precipitation approach, and (ii) a non-aqueous sol–gel approach. This innovative configuration obtains IONs in a very short reaction time, with a small size, narrow distribution and better magnetic properties than those obtained using the microwave oven type reactors, and the classical drawbacks of the MW-assisted processes are overcome.

Experimental

Materials

Iron(II) chloride tetra-hydrate (FeCl₂·4H₂O, 99%), iron(III) chloride hexa-hydrate (FeCl₃·6H₂O, 99.9%) and iron(III) acetylacetonate (Fe(acac)₃, 97%) purchased from Sigma-Aldrich were used as iron precursor salts. Sodium hydroxide (NaOH, Carlo Erba) was used as a hydrolyzing agent. Tetra methyl ammonium hydroxide (25 wt%) was purchased from Sigma-Aldrich and was used as stabilizing agent. Deionized water obtained with a Milli-Q system (Millipore, Bedford, MA, USA) and anhydrous ethanol purchased from Fluka Analytical (99.9%) were used as solvents for IONs synthesis in the hydrothermal route. Benzyl alcohol and ethanol (99.9%), which were used as solvents for the non-aqueous sol–gel route and the solvothermal synthesis, were purchased from Sigma-Aldrich and were used as received.

Nanoparticle microwave-assisted synthesis

The synthesis was performed using a 250 ml homemade stainless steel pressurized reactor, equipped with a coaxial antenna as a microwave applicator. The reactor is composed of a stainless steel cylindrical chamber with two circular caps closed with several bolts. The top cap has a deep recess that is made using a closed-end quartz tube. The seal between the stainless steel cap and the quartz tube is ensured by an O-ring. The recess is used to introduce the coaxial antenna providing the MW power. The reactor has two other connections for the introduction of the temperature probe (type K thermocouple) and to connect it to a nitrogen cylinder with a relative pressure meter (DS Europe, mod. LP 652-100). The 100 ml sample holder was made with Teflon and shaped to reduce the transmission of heat to the steel walls of the reactor.^44,47

The source of the microwave is a magnetron oscillator equipped with forward and reflected power indicators (SAIREM, Mod. GMP 03 K/SM, up to 300 W of continuous MW irradiation power at a frequency of 2.45 GHz). A satisfactory MW impedance matching between the reactor and the MW source was obtained by configuring the active section of the applicator as a function of the permittivity of the reagents. The exposed applicator tip is provided with a threaded metal cap whose position is a function of the dielectric permittivity of the reagents. It was therefore possible to reduce the reflected power to zero from the reactor to the MW source.

The reactor is equipped with pressure and temperature sensors. A versatile PID control approach is used since the system can operate in two ways: isothermally when the power is regulated or adiabatically when the power is kept constant. The latter causes a constant temperature increase, within limits, until the power is switched off.

Details of the two different approaches used for the fabrication of the IONs are reported below illustrated in Scheme 1(a). The homemade reactor used is illustrated in Scheme 1(b).

Scheme 1 Schematic representation of (a1) solvothermal and (a2) non-aqueous sol–gel MW assisted syntheses and (b) the microwave high pressure reactor.

Solvothermal synthesis. The synthesis was performed following the modified hydrothermal MW-assisted method, described elsewhere for a traditional microwave reactor.²⁰ From the point of view of user safety, this reactor is a closed space, which does not emit any stray radiation except for hole hosting the recess used for the antenna. The stray radiation emitted from here is greatly reduced using the choke, a metallic co-axial conductive portion with a higher diameter than the open-end coaxial applicator cable. A power meter is used to continuously monitor the stray radiation and ensure it is always within the safe region.

A typical reaction was performed by loading the reactor with a mixture of 15 ml of 0.05 M of iron(II) chloride (0.75 mmol) aqueous solution and 30 ml of 0.05 M of iron(III) chloride (1.5 mmol) aqueous solution (IONs-1, hydrothermal synthesis) or ethanol/water (40/60 v/v) medium (IONs-2, solvothermal synthesis). A 20% NaOH solution was added dropwise under vigorous stirring up to pH 12 directly in the reactor. A red suspension was formed suggesting the presence of a metastable Fe³⁺ oxyhydroxide, ferrihydrite (Fe₅O₇(OH)·4H₂O). At this point, the reactor was closed and the mixture was stirred at 700 RPM, irradiated with 230 W up to 150 °C, and maintained at this temperature for 5 minutes. After MW treatment, the power supply was switched off and the reactor was quenched in a cool water bath.

Samples were separated by centrifugation (4000 RPM for 10 minutes), washed with distilled Milli-Q water to remove the excess base until the pH of the supernatant medium was neutral, and were then separated by adding ethanol (50 ml) followed by centrifugation (4000 rpm for 15 minutes). The supernatant was removed and the solid was dispersed in a tetra methyl ammonium hydroxide solution (25 wt%).

Non-aqueous sol–gel synthesis. The synthesis was performed following the modified sol–gel microwave-assisted method, described elsewhere for a traditional microwave reactor.⁴⁸ A typical reaction was performed by loading the reactor with 2.5 g of Fe(acac)₃ (7.1 mmol) dissolved in 52.5 g (50 ml) of benzyl alcohol (IONs-3). The reactor was closed and the mixture was stirred at 700 RPM, irradiated with 230 W up to 60 °C and maintained at this temperature for 5 minutes to achieve complete dissolution of the iron precursor. It was then heated to 200 °C and kept at this temperature for 15 min. After MW treatment, the power supply was switched off and the reactor was quenched in a cool water bath. Samples were separated by adding ethanol (60 ml), followed by centrifugation (4000 RPM for 20 minutes). They were then washed with ethanol and dried in a vacuum at room temperature.

Characterization of iron oxide nanoparticles

Transmission electron microscopy. The size and morphology of the IONs were examined by transmission electron microscopy (TEM). The powders were suspended in 2 ml of isopropanol and a few drops of the suspensions were deposited onto copper grids. The solvent was then left to evaporate at room temperature. Images were acquired using a CM12 Philips transmission electron microscope equipped with a microanalysis Edax and LaB6 cathode.

Thermogravimetry. A TA Instruments Thermobalance model Q5000 equipped with an FTIR Agilent Technologies spectrophotometer model Cary 640 for evolved gas analysis (EGA) was used. TG measurements were performed at a rate of 10 °C min⁻¹, from 30 °C to 700 °C under air flow (25 ml min⁻¹).

TG-FTIR measurements were performed at a rate of 20 °C min⁻¹, from 30 °C to 700 °C under nitrogen flow (80 ml min⁻¹), from 600 to 4000 cm⁻¹ with a slit (4 cm⁻¹ in width). To reduce the strong background absorption from water and carbon dioxide in the atmosphere in the TG-FTIR spectra, the optical bench was purged with nitrogen. In addition, a background spectrum was taken before the beginning of each analysis in order to zero the signal in the gas cell and to eliminate any contribution from ambient water and carbon dioxide. The amount of sample in each TG measurement varied between 2 and 3 mg. Each experiment was performed three times.

X-ray powder diffraction measurements. The crystalline phase of the particles was studied by X-ray powder diffraction (XRD) using a Bruker New D8 ADVANCE ECO diffractometer equipped with a Cu Kα radiation source. Diffractograms were collected in the 25–70° 2θ range, with a step size of 0.03° and a collection time of 1 s. Quantitative analysis of the XRD data was undertaken with a full pattern fitting procedure based on the Rietveld method using the Topas program.

ATR-FTIR spectra measurements. Infrared spectra were recorded using an FT-IR Agilent Technologies Spectrophotometer model Cary 640, equipped with a universal attenuated total reflectance accessory (ATRU). A few micrograms of IONs powder were used with the following spectrometer parameters – resolution: 4 cm⁻¹, spectral range: 500–4000 cm⁻¹, number of scans: 16. Spectrum software was used to process the FTIR spectra.

Magnetic measurements. Magnetization (M) and magnetic susceptibility (χ) measurements on the IONs powders were conducted on a Quantum Design MPMS-XL-5 Superconducting Quantum Interference Device (SQUID) magnetometer equipped with a 50 kOe magnet. Susceptibility χ(T) was recorded in the temperature range 2–300 K, with a magnetic field of 100 Oe (μ₀H = 10 mT). Isothermal magnetization data M(H) were obtained at 300 K and at 5 K in the range −50/+50 kOe. In order to perform these experiments, powder samples were pressed into diamagnetic pharmaceutic capsules.

Results and discussion

Two different methodologies assisted by coaxial MW technology, namely solvothermal and non-aqueous sol–gel synthesis, were performed in order to obtain iron oxide nanoparticles with a small size and different physicochemical properties in a fast reaction time.

Particle sizes

As reported in the literature,^20,49 the growth mechanism of IONs occurs in two steps (see Scheme 1a). When MW assisted solvothermal synthesis is used, the first step is the formation of a metastable Fe³⁺ oxyhydroxide, ferrihydrite (Fe₅O₇(OH)·4H₂O), induced by a rapid increase of pH. In the second step, the reaction with Fe²⁺ ions in solution forms nanoparticles (see Scheme 1a1).²⁰ On the other hand, when MW assisted non-aqueous sol–gel synthesis is used, the first step is the solvolysis of the precursor involving ligand exchange. The second step is the condensation with the formation of iron-oxygen-iron clusters evolving in iron oxide nanocrystals (see Scheme 1a2).⁴⁹

Fig. 1 reports TEM images of all samples and histogram of the particle size distributions of the IONs-2 and IONs-3 samples. Table 1 summarizes a literature review of the microwave-assisted IONs synthesis approaches including the hydrothermal synthesis,^33,34 the non-hydrolytic sol–gel route,^35–38 the polyol approach,^7,39,40 and the solvothermal synthesis^41,42 together with our results. The data collected in Table 1 clearly show that the coaxial MW-assisted hydrothermal synthesis gave better results than the conventional MW-assisted hydrothermal approach using the oven type reactors. Highly aggregated IONs-1 with a non-well-defined morphology (see Fig. 1a) were obtained by the hydrothermal approach using pure water as a solvent. When the polarity of the reaction medium was modified (mixture of ethanol/water), highly dispersed IONs and stable nanoparticles with a well-defined morphology (mostly spherical, see Fig. 1b) were produced (IONs-2). In this case we obtained smaller IONs-2 (6.1 nm) and at a lower reaction temperature (150 °C) than those reported by Hu et al. (2011),²⁰ (17 nm, T = 200 °C) which represent the best result in the literature (see Table 1). Well-dispersed and ultra-small magnetic IONs, with a main particle size ranging from 4 to 7 nm, were synthesized by the non-aqueous sol–gel methodology (IONs-3, solvent benzyl alcohol, T = 200 °C, see Fig. 1d), for the most part matching the best results from the literature (5.4 nm, T = 160 °C, see Table 1).³⁶

Fig. 1 TEM images of magnetic nanoparticles IONs-1 (a), IONs-2 (b) and IONs-3 (d) and histograms of the particle size distribution of IONs-2 (c) and IONs-3 (e).

Table 1 Reaction parameters (iron salt precursor, temperature, time and solvent) physicochemical properties (crystal phase, particle size and saturation magnetization, M_s) and surface coating of the IONs which were reported in the literature and in this work

MW synthesis	Reaction conditions				IONs physicochemical properties				Ref.
	Iron salt precursor	Temp. (°C)	Time (min)	Solvent	Iron oxide crystal phase	Particle size (nm)	Ms (emu g^−1) T = 300K	Surface coating
a N.R. = not reported.b Aggregated NP clusters were detected.c adsorption of the mentioned ion molecule by coordination with surface hydroxyl groups of IONs is observed.d Determined by TEM analysis.e Determined by XRD analysis.f Determined by magnetic analysis.
Hydrothermal	FeCl2	200	6	Ethanol/water (1 : 2)	Fe3O4	22	N.R.^a	Bare	20
	FeCl3				α-Fe2O3	49–91		Bare
	FeCl2/FeCl3				Fe3O4/γ-Fe2O3	17		Bare
	FeCl2/FeCl3 (IONs-2)	150	5	Ethanol/water (1 : 2)	γ-Fe2O3	6.1 ± 0.8^d	60	Bare	This work
						6.9^e
						7.2^f
	FeCl2/FeCl3	60	120	Water	Fe3O4/γ-Fe2O3	13.5	72.9	Citric acid	15
	FeSO4	85	30	Water	Fe3O4/γ-Fe2O3	13.8	72	Bare	50
	FeCl3	220	25	Water	α-Fe2O3	100	N.R.^a	Phosphate^c	33
	FeSO4/FeCl3	150	25	Water	γ-Fe2O3	10	40	Bare	34
	FeCl3	100	10	Water	Fe3O4/γ-Fe2O3	30–50	60	Dextran	9
	FeCl2/FeCl3 (IONs-1)	150	5	Water	γ-Fe2O3	—^b	68	Bare	This work
						6.9^e
						7.3^f
Non-aqueous sol–gel	Fe(acac)3	180	10	Benzyl alcohol	γ-Fe2O3	7.2	60	Citrated	35
	Fe(acac)3	160	5	Benzyl alcohol	Fe3O4/γ-Fe2O3	5.4	60	Oleic acid	36
	Fe(acac)3	200	240	Benzyl alcohol	Fe3O4/γ-Fe2O3	7.4	N.R.^a	N.R.	38
	Fe(acac)3	200	15	Benzyl alcohol	Fe3O4	5.4	42.5	Benzoate^c	48
	Fe(acac)3	200	15	Benzyl alcohol	γ-Fe2O3	5.5 ± 0.9^d	63	Benzaldehyde^c	This work
						4.7^e
						5.4^f
Other solvothermal	FeSO4	80	240	Cyclohexane/1-pentanol/water	α-Fe2O3	270–310	0.104	Bare	42
	FeCl3	160			α-Fe2O3	120	0.011	Bare
	FeCl3	200	50	Ethylene glycol	Fe3O4	100–400	58–76.9	Polyacids^c	39
	FeCl3	200	15	Ethylene glycol	Fe3O4	100	63	PEG-20000	40
	FeCl3	160	60	Ethylene glycol	Fe3O4	15	37.1	N.R.	7
	Fe(CO)5	200	20	2-Propyl alcohol	γ-Fe2O3	20	62	N.R.	41

---

Crystalline phases analysis

Powder X-ray diffraction is the experimental technique commonly used to analyze the crystalline phase of a sample.⁵¹ Fig. 2 shows the X-ray powder diffraction patterns for the three IONs samples synthesized in this work. All samples have a cubic spinel type structure with a lattice constant a of 0.8335, 0.8334 and 0.8344 nm for IONs-1, IONs-2 and IONs-3 respectively. Rietveld analysis gave values for the average crystallite size in the three samples (see Table 1). By comparing these data with those extracted from TEM analysis, it is possible to exclude the presence of bulk-like portions of iron oxides in the samples, which might not be found by TEM inspection. The crystallite size of IONs-1 results in the same size range as the other samples (6.9 nm), indicating that macroscopic aggregation is not reflected in the microscopic structure of the sample. The average crystallite size in IONs-2 was found to be very similar to the average particle size obtained through TEM analysis, suggesting that the particles in the sample are mostly single crystals. In the case of IONs-3 on the other hand, the average crystallite size is smaller than the mean particle size (4.7 nm against 5.5 nm), which suggests that particles in this sample are polycrystalline. While in bulk oxides the XRD diffraction pattern allows a dependable distinction between magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃) phases, in nanostructured systems the broadening of the diffraction peaks introduces a degree of uncertainty in the determination of cell parameters for which a degree of uncertainty remains. With this caveat in mind, the cell parameters suggest that all 3 samples are predominantly composed of maghemite.

Fig. 2 X-ray powder diffraction patterns for the three nanoparticle samples.

Fig. 3 ATR-FTIR spectra of samples IONs-1, IONs-2 and IONs-3.

FTIR and TG characterization

In Fig. 3 ATR-FTIR spectra of samples IONs-1, IONs-2 and IONs-3 are shown.​ The characteristic absorption bands of the Fe–O bonds in bulk iron oxides are 570 and 375 cm⁻¹.⁵² In IONs, these two bands shift to higher wavenumbers at about 600 and 440 cm⁻¹, due to the breaking of a large number of bonds for surface atoms which result in a rearrangement of delocalized electrons on the particle surface.⁵³ As a result, the surface bond force constant increases as iron oxides are reduced to nanoparticles, thus a blue-shift of absorption of the Fe–O bond can be observed. This shift was higher in the IONs-3 (444, 630 cm⁻¹) compared to IONs-1 (442, 584 cm⁻¹) and IONs-2 (437, 588 cm⁻¹). This phenomenon can be explained by taking into account the presence of benzaldehyde (C=O stretching at 1697 cm⁻¹ and aromatic stretching and bending vibration modes in the range 1000–1580 cm⁻¹), formed as the oxidation product of benzyl alcohol during the reduction of Fe(III) ions, in the spectrum of IONs-3.⁵³ The interaction of Fe–O–H groups on the nanoparticles surface with –C=O moiety of benzaldehyde could lead to the enhancement of the bond force constant for Fe–O bonds with a shift to higher wavenumbers.⁵³

The presence of benzaldehyde in IONs-3 was confirmed by the TG data (Fig. 4 and Table 2). The TG of IONs-1 and IONs-2 samples showed the typical profile of bare iron oxide nanoparticles, with a small mass loss under 100 °C (about 2%) and a second mass loss at 280 °C (2.4–2.8%) due to the weakly-bonded and adsorbed water, respectively. This was confirmed by TG-FTIR analysis which showed the signal of water in both mass losses. The TG of the IONs-3 sample showed a mass loss under 100 °C (1.6%) probably due to the loss of residues of benzyl alcohol used in the synthesis and a second mass loss at 323 °C (7.6%), ascribed to the oxidation products of benzyl alcohol, such as, benzaldehyde. The spectrum of the gases evolved by the IONs-3 sample at 323 °C showed a peak in the range 1500–1600 cm⁻¹ and peaks at 814, 700 and 760 cm⁻¹ due to C=C stretching and aromatic ring C–H bending, and signals at 2113 and 2180 cm⁻¹ due to carbon monoxide formed during the benzaldehyde degradation. Considering that the mass residues at 700 °C are composed of Fe₂O₃, as previously shown by XRD data, we calculated the iron content of each ION sample and the obtained values are reported in Table 2.

Fig. 4 Thermogravimetric curves (a) and their derivatives (b) of IONs samples performed under air flow at 10 °C min⁻¹ heating rate.

Table 2 Experimental temperatures and percentage mass losses of thermal degradation steps in the temperature range 25–700 °C, residues at 700 °C and iron content of IONs samples

Step	Temperature of the step (mass loss%)
	IONs-1	IONs-2	IONs-3
1	36 °C (2.4%)	35 °C (2.4%)	78 °C (1.6%)
2	280 °C (2.8%)	278 °C (2.4%)	323 °C (7.6%)
Residual mass at 700 °C	94.9%	95.2%	90.8%
Iron content (%)	66.4%	66.6%	63.5%

---

Magnetic properties

The magnetic properties of the IONs were investigated and compared. The magnetization and magnetic susceptibility values were normalized per gram of magnetic material in the IONs, calculated from the iron percentage of the samples.

The magnetic measurements were performed on the powder samples using a superconducting quantum interference device (SQUID) magnetometer. The zero-field-cooled/field-cooled (ZFC/FC) magnetic susceptibility curves were recorded in a temperature range of 2–300 K, with a magnetic field of 100 Oe (μ₀H = 10 mT). The ZFC/FC curves are reported in Fig. 5 and show the typical profiles of a set of single domain magnetic sphere nanoparticles.⁵⁴

Fig. 5 Zero-field-cooled (ZFC) and field-cooled (FC) magnetic susceptibility curves (emu g⁻¹ Fe₂O₃) of the three IONs samples, measured in a magnetic field 100 Oe from 2 K to 300 K. Symbols (), () and () refer to IONs-1, IONs-2 and IONs-3, respectively.

As the temperature is increased, a decrease of χ is observed in the “FC” part, while a maximum is observed in the “ZFC” part. As shown in Fig. 5, this behaviour is clear for the IONs-3 sample, while it is less obvious for IONs-1 and IONs-2 samples, since the maximum is reached above 300 K.

The average blocking temperatures of the nanoparticles, which are associated with the temperature (T_max) at which the ZFC curve reaches its maximum, are reported in Table 3. As can be seen, in the case of IONs-3 T_max is 96 K, while in case of IONs-1 and IONs-2 the trend of ZFC/FC curves is more complex. In particular, in case of IONs-1, a local maximum in the ZFC curve at about 240 K can be seen with a further increase of the trend above 300 K. In case of IONs-2, the blocking temperatures of the nanoparticles is above 300 K.

Table 3 The particle's magnetic moment μ_p (BM), blocking temperatures T_B (K), and saturation magnetization M_s (emu g⁻¹ Fe₂O₃) at 300 K and 5 K of the nanoparticles investigated

Samples	μp (BM)	Tmax	Ms (emu g^−1) (T = 300 K)	Ms (emu g^−1) (T = 5 K)
a A local maximum is observed at about 240 K.
IONs-1	13.700	Above 300 K^a	68	76
IONs-2	12.000	Above 300 K	60	66
IONs-3	4.700	96 K	63	76

---

The magnetization as a function of the applied magnetic field was measured in the range ±50 kOe at T = 300 K and at T = 5 K. The magnetization curves of nanoparticles, normalized per gram of magnetic material (Fe₂O₃), are reported in Fig. 6. Both magnetization trends recorded at 300 K and 5 K show a typical superparamagnetic behaviour.^55–57 Fig. 6 shows that below the blocking temperature at 5 K a small hysteresis with a coercive field of the order of 400 Oe is measured for the samples.

Fig. 6 Trend of the magnetization M (emu g⁻¹ Fe₂O₃) measured at T = 300 K (top) and T = 5 K (bottom) as a function of the external magnetic field H (kOe). In this latter case, the inset reports an enlargement showing the hysteresis loops for all samples. Symbols (), () and () refer to IONs-1, IONs-2 and IONs-3, respectively.

The M(H) dependence of the magnetization curves at 300 K reported in Fig. 6 (top) can be described by the Langevin theory of paramagnetism,⁵⁶ by applying the following eqn (1):

where M_s is the saturation magnetization, L the Langevin function, and μ_p the particle's magnetic moment. While for the IONs-3, the application of (1) is fully justified (the blocking temperature is well below the 300 K), this is not the case for IONs-1 and IONs-2. However, despite the blocking temperature for the latter two samples being above room temperature, the fit with (1) is good enough and the fitting parameters can give us a good approximation of the average magnetic moment of the nanoparticles. The μ_p values obtained are reported in Table 3 together with the saturation magnetization M_s (emu g⁻¹ Fe₂O₃) at 300 K and 5 K. In principle, from these data we can estimate the average diameter of the nanoparticles, by assuming a spherical shape. In fact, the particle's magnetic moment is related to the volume of a spherical particle, according to: μ_p = M_sπd³/6. For IONs-3 sample, this is fully justified and the average nanoparticle diameter from magnetic measurements is about 5.4 nm. In the other two cases, the obtained value of d is 7.2 and 7.3 nm, for IONs-1 and IONs-2, respectively.

Conclusions

Iron oxide nanoparticles with superparamagnetic properties were synthesized in a fast and a simple MW-assisted process using a coaxial antenna to apply the MW energy inside the high pressure reactor. The coaxial antennas made it possible to radiate large volumes, simply by inserting the antennas in the reactor, at various depths. In fact, it is possible to set up any desired number of applicators in an arbitrarily large volume. The absence of a resonant cavity implies that the electromagnetic field does not reach high values and is more uniform with respect to the microwave ovens. In particular, there is no formation of hot-spots which implies a more uniform and higher quality thermal treatment.

This versatile configuration was combined with different microwave absorbing media, such as benzyl alcohol and ethanol/water, in order to tune the magnetic and physicochemical properties of the IONs synthesized.

Benzyl alcohol interacted strongly with the IONs surface thus producing highly dispersed and stable nanoparticles with a well-defined morphology and size below 6 nm (IONs-3). This interaction was also revealed by the TG and FTIR analysis. The use of water as a reaction medium produced IONs without functional groups but with a stronger saturation magnetization (IONs-1 and IONs-2).

In conclusion, the proposed methodologies using the coaxial MW configuration produced IONs with physicochemical characteristics that are in line with the best literature results.

Moreover, considering the surface affinity to a hydrophobic (IONs-3) or hydrophilic (IONs-1 and IONs-2) medium and their magnetic properties, the IONs synthesized can be used in various biomedical applications, including drug delivery systems or efficient contrast agents in MRI, while the novel coaxial MW approach used overcomes the classical drawbacks shown by the oven type MW configurations.

Acknowledgements

This work was supported by the projects PRIN 2010–2011 (No. 2010C4R8M8) and FIRB 2012 (No. RBFR12ETL5), funded by the Italian Ministry of University and Research, and by the project PRA_2015_0055 and PRA_2016_46 funded by the University of Pisa.

Notes and references

1. W. Wu, Z. Wu, T. Yu, C. Jiang and W.-S. Kim, Sci. Technol. Adv. Mater., 2015, 16, 23501.
2. Y. Jun, J. Choi and J. Cheon, Chem. Commun., 2007, 1203–1214.
3. A. H. Lu, E. L. Salabas and F. Schüth, Angew. Chem., Int. Ed., 2007, 46, 1222–1244.
4. R. Zboril, M. Mashlan and D. Petridis, Chem. Mater., 2002, 14, 969–982.
5. B. Movassagh and A. Yousefi, Monatsh. Chem., 2015, 146, 135–142.
6. P. D. Stevens, J. Fan, H. M. R. Gardimalla, M. Yen and Y. Gao, Org. Lett., 2005, 7, 2085–2088.
7. Z. Ai, K. Deng, Q. Wan, L. Zhang and S. Lee, J. Phys. Chem. C, 2010, 114, 6237–6242.
8. H. Y. Lee, N. H. Lim, J. A. Seo, S. H. Yuk, B. K. Kwak, G. Khang, H. B. Lee and S. H. Cho, J. Biomed. Mater. Res., Part B, 2006, 79, 142–150.
9. E. a. Osborne, T. M. Atkins, D. a. Gilbert, S. M. Kauzlarich, K. . Liu and A. Y. Louie, Nanotechnology, 2012, 23, 215602.
10. E. Terreno, D. D. Castelli, A. Viale and S. Aime, Chem. Rev., 2010, 110, 3019–3042.
11. S. Laurent, D. Forge, M. Port, A. Roch, C. Robic, L. Vander Elst and R. N. Muller, Chem. Rev., 2008, 108, 2064–2110.
12. T. D. Schladt, K. Schneider, H. Schild and W. Tremel, Dalton Trans., 2011, 40, 6315–6343.
13. L. Douziech-Eyrolles, H. Marchais, K. Hervé, E. Munnier, M. Soucé, C. Linassier, P. Dubois and I. Chourpa, Int. J. Nanomed., 2007, 2, 541–550.
14. T. K. Jain, M. A. Morales, S. K. Sahoo, D. L. Leslie-Pelecky and V. Labhasetwar, Mol. Pharm., 2005, 2, 194–205.
15. C. Blanco-Andujar, D. Ortega, P. Southern, Q. a. Pankhurst and N. T. K. Thanh, Nanoscale, 2015, 7, 1768–1775.
16. S. Laurent, S. Dutz, U. O. Hafeli and M. Mahmoudi, Adv. Colloid Interface Sci., 2011, 166, 8–23.
17. A. C. Silva, T. R. Oliveira, J. B. Mamani, S. M. F. Malheiros, L. Malavolta, L. F. Pavon, T. T. Sibov, E. Amaro, A. Tannús, E. L. G. Vidoto, M. J. Martins, R. S. Santos and L. F. Gamarra, Int. J. Nanomed., 2011, 6, 591–603.
18. a Gupta and M. Gupta, Biomaterials, 2005, 26, 3995–4021.
19. W. Wu, X. H. Xiao, F. Ren, S. F. Zhang and C. Z. Jiang, J. Low Temp. Phys., 2012, 168, 306–313.
20. L. Hu, A. Percheron, D. Chaumont and C. H. Brachais, J. Sol-Gel Sci. Technol., 2011, 60, 198–205.
21. A. Willis, N. Turro and S. O'Brien, Chem. Mater., 2005, 3, 5970–5975.
22. S. Dolci, V. Ierardi, M. Remskar, Z. Jagličić, F. Pineider, A. Boni, G. Pampaloni, C. A. Veracini and V. Domenici, J. Mater. Sci., 2013, 48, 1283–1291.
23. X. Zhang, Y. Niu, X. Meng, Y. Li and J. Zhao, CrystEngComm, 2013, 15, 8166–8172.
24. M. I. Khalil, Arabian J. Chem., 2015, 8, 279–284.
25. A. E. Regazzoni, G. A. Urrutia, M. A. Blesa and A. J. G. Maroto, J. Inorg. Nucl. Chem., 1981, 43, 1489–1493.
26. B. R. V. Narasimhan, S. Prabhakar, P. Manohar and F. D. Gnanam, Mater. Lett., 2002, 52, 295–300.
27. T. Hyeon, S. S. Lee, J. Park, Y. Chung and H. B. Na, J. Am. Chem. Soc., 2001, 123, 12789–12801.
28. K. V. P. M. Shafi, A. Ulman, X. Yan, N. Yang, C. Estourne, H. White and M. Rafailovich, Langmuir, 2001, 17, 5093–5097.
29. K. Wongwailikhit and S. Horwongsakul, Mater. Lett., 2011, 65, 2820–2822.
30. S. Ge, X. Shi, K. Sun, C. Li, J. R. Baker, M. M. Banaszak Holl and B. G. Orr, J. Phys. Chem. C, 2009, 113, 13593–13599.
31. M. Zhu and G. Diao, J. Phys. Chem. C, 2011, 115, 18923–18934.
32. M. Zhu, Y. Wang, D. Meng, X. Qin and G. Diao, J. Phys. Chem. C, 2012, 116, 16276–16285.
33. X. Hu, J. C. Yu, J. Gong, Q. Li and G. Li, Adv. Mater., 2007, 19, 2324–2329.
34. V. Sreeja and P. A. Joy, Mater. Res. Bull., 2007, 42, 1570–1576.
35. E. Carenza, V. Barceló, A. Morancho, J. Montaner, A. Rosell and A. Roig, Acta Biomater., 2014, 10, 3775–3785.
36. O. Pascu, E. Carenza, M. Gich, S. Estradé, F. Peiró, G. Herranz and A. Roig, J. Phys. Chem. C, 2012, 116, 15108–15116.
37. C. Sciancalepore, R. Rosa, G. Barrera, P. Tiberto, P. Allia and F. Bondioli, Mater. Chem. Phys., 2014, 148, 117–124.
38. C. Sciancalepore, F. Bondioli, T. Manfredini and A. Gualtieri, Mater. Charact., 2015, 100, 88–97.
39. S. Liu, F. Lu, X. Jia, F. Cheng, L.-P. Jiang and J.-J. Zhu, CrystEngComm, 2011, 13, 2425–2429.
40. D. P. Yang, F. Gao, D. X. Cui and M. Yang, Curr. Nanosci., 2009, 5, 485–488.
41. W. E. Mahmoud, F. Al-Hazmi, F. Al-Noaiser, a. a. Al-Ghamdi and L. M. Bronstein, Superlattices Microstruct., 2014, 68, 1–5.
42. F. N. Sayed and V. Polshettiwar, Sci. Rep., 2015, 5, 9733.
43. V. Ragaini, C. Pirola, S. Borrelli, C. Ferrari and I. Longo, Ultrason. Sonochem., 2012, 19, 872–876.
44. J. González-Rivera, I. R. Galindo-Esquivel, M. Onor, E. Bramanti, I. Longo and C. Ferrari, Green Chem., 2014, 16, 1417–1425.
45. J. Gonzalez Rivera, C. Duce, D. Falconieri, C. Ferrari, L. Ghezzi, A. Piras and M. R. Tiné, Innovative Food Sci. Emerging Technol., 2016, 33, 308–318.
46. J. Gonzalez-Rivera, A. Spepi, C. Ferrari, C. Duce, I. Longo, D. Falconieri, A. Piras and M. R. Tiné, Green Chem., 2016 10.1039/c6gc02200f.
47. J. González-Rivera, J. Tovar-Rodríguez, E. Bramanti, C. Duce, I. Longo, E. Fratini, I. R. Galindo-Esquivel and C. Ferrari, J. Mater. Chem. A, 2014, 2, 7020–7033.
48. C. Sciancalepore, R. Rosa, G. Barrera, P. Tiberto, P. Allia and F. Bondioli, Mater. Chem. Phys., 2014, 148, 117–124.
49. I. Grabs, C. Bradtmöller, D. Menzel and G. Garnweitner, Cryst. Growth Des., 2012, 12, 1469–1475.
50. S. Kalyani, J. Sangeetha and J. Philip, J. Nanosci. Nanotechnol., 2015, 15, 5768–5774.
51. W. S. Galvao, R. M. Freire, T. S. Ribeiro, I. F. Vasconcelos, L. S. Costa, V. N. Freire, F. A. M. Sales, J. C. Denardin and P. B. A. Fechine, J. Nanopart. Res., 2014, 16, 2803.
52. R. D. Waldron, Phys. Rev., 1955, 99, 1727–1735.
53. M. Ma, Y. Zhang, W. Yu, H. Y. Shen, H. Q. Zhang and N. Gu, Colloids Surf., A., 2003, 212, 219–226.
54. M. Tadic, M. Panjan, V. Damnjanovic and I. Milosevic, Appl. Surf. Sci., 2014, 320, 183–187.
55. C. M. Sorensen, in Nanoscale Materials in Chemistry, John Wiley & Sons, Inc., 2001, pp. 169–221.
56. S. Dolci, V. Ierardi, A. Gradisek, Z. Jaglicic, M. Remskar, T. Apih, M. Cifelli, G. Pampaloni, C. Veracini and V. Domenici, Curr. Phys. Chem., 2013, 3, 493–500.
57. S. Dolci, V. Domenici, C. Duce, M. R. Tiné, V. Ierardi, U. Valbusa, Z. Jaglicic, A. Boni, M. Gemmi and G. Pampaloni, Mater. Res. Express, 2014, 1, 35401.

---