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PEG 200 DILAURATE

CAS NO: 9005-02-1

Polyethylene Glycol 200 Dilaurate, commonly referred to as PEG 200 DILAURATE, is a polyether compound that is used in a wide variety of fields including pharmaceutical manufacturing as an excipient and active ingredient. Due to its low toxicity it can be used as a lubricating coating for various surfaces in aqueous and non-aqueous environments, a reagent in biochemistry to create very high osmotic pressures, a polar stationary phase for gas chromatography and as a binder. Ungraded products supplied by Spectrum are indicative of a grade suitable for general industrial use or research purposes and typically are not suitable for human consumption or therapeutic use.

Synonyms:

PEG-4 Dilaurate; ; Glycol dilaurate; Ethylene glycol dilaurate; 624-04-4; Ethylene dilaurate; Ethylene laurate; Dodecanoic acid, 1,2-ethanediyl ester; Ethylene glycol didodecanoate; UNII-9O691KKR2A; 2-dodecanoyloxyethyl dodecanoate; 9O691KKR2A; Dodecanoic acid, 1,1'-(1,2-ethanediyl) ester; Lauric acid, ethylene ester; PEG-4 Dilaurate; PEG-6 Dilaurate; PEG-8 Dilaurate; PEG-12 Dilaurate; PEG-20 Dilaurate; PEG-32 Dilaurate; PEG-75 Dilaurate; PEG-150 Dilaurate; Polyoxyethylene (2) dilaurate; Polyoxyethylene (4) dilaurate; Polyoxyethylene (6) dilaurate; Polyoxyethylene (8) dilaurate; Polyoxyethylene (12) dilaurate; Polyoxyethylene (20) dilaurate; Polyoxyethylene (32) dilaurate; Polyoxyethylene (75) dilaurate; Polyoxyethylene (150) dilaurate; Oxydi-2,1-ethanediyl dodecanoate; Polyethylene glycol (2) dilaurate; Polyethylene glycol 100 dilaurate; Polyethylene glycol 200 dilaurate; Polyethylene glycol 300 dilaurate; Polyethylene glycol 400 dilaurate; Polyethylene glycol 600 dilaurate; Polyethylene glycol 1000 dilaurate; Polyethylene glycol 1540 dilaurate; Polyethylene glycol 4000 dilaurate; Polyethylene glycol 6000 dilaurate; EINECS 210-827-0; NSC 406565; AI3-03485; Dodecanoic acid, oxydi-2,1-ethanediyl ester; UNII-9G87YOO1GV; UNII-FC11NGP7E6; UNII-FQ9T18W7BU; 9G87YOO1GV; FC11NGP7E6; FQ9T18W7BU; UNII-4U29QAW23A; UNII-8N26TNM70C UNII-9J99P5NN1F; UNII-KCR71CW036; UNII-TWV5J70L88; 9005-02-1; SCHEMBL461558; UNII-CF607I8E19; UNII-K881554QIN; ethane-1,2-diyl didodecanoate; 1,2-Dilauroyl ethylene glycol; 4U29QAW23A; 8N26TNM70C; 9J99P5NN1F; KCR71CW036; TWV5J70L88; DTXSID0060779; CF607I8E19; Dodecanoic acid,2-ethanediyl ester; K881554QIN; Lauric acid, 1,2-ethanediyl ester; Lauric acid, ethylene ester (8CI); 6744AF; NSC406565; ZINC95680706; Poly(oxy-1,2-ethanediyl), alpha-(1-oxododecyl)-omega-((1-oxododecyl)oxy)-; NSC-406565; DB-054155; FT-0632625; D-4250; Q27272813

Polyethylene glycol (PEG) is a polyether compound with many applications from industrial manufacturing to medicine.
Polyethylene glycol is a condensation polymers of ethylene oxide and water with the general formula H(OCH2CH2)nOH, where n is the average number of repeating oxyethylene groups typically from 4 to about 180. The low molecular weight members from n=2 to n=4 are diethylene glycol, triethylene glycol and tetraethylene glycol respectively, which are produced as pure compounds. The low molecular weight compounds upto 700 are colorless, odorless viscous liquids with a freezing point from -10 C (diethylene gycol), while polymerized compounds with higher molecular weight than 1,000 are waxlike solids with melting point upto 67 C for n 180. The abbreviation (PEG) is termed in combination with a numeric suffix which indicates the average molecular weights. One common feature of PEG appears to be the water-soluble. It is soluble also in many organic solvents including aromatic hydrocarbons (not aliphatics).

They are used to make emulsifying agents and detergents, and as plasticizers, humectants, and water-soluble textile lubricants.Polyethylene glycol is non-toxic, odorless, neutral, lubricating, nonvolatile and nonirritating and is used in a variety of pharmaceuticals and in medications as a solven, dispensing agent, ointment and suppository bases, vehicle, and tablet excipient. Lipophilic compounds are ethoxylated ethylene oxide (the monomer of polyglycols) so that the target compounds have hydrophilic (soluble in water). The bifunctionality in one molecule provides the basic properties of surfactants. Fatty acids rather lipophilic (or hydrophobic) exhibiting low HLB (Hydrophilic-Lipophilic Balance) values; having an affinity for, tending to combine with, or capable of dissolving in lipids (or water-insoluble). While, the ethoxylated fatty acids are hydrophilics exhibiting high HLB values; having an affinity for water; readily absorbing or dissolving in water. The type of fatty acid and the mole number of ethylene oxide provides diverse HLB values for proper applications.

There are almost infinite ethoxylated compounds. In combination with the average molecular weights and water-soluble property of PEG, the wide range of chain lengths of fatty acids provide identical physical and chemical properties for the proper application selections directly or indirectly.

•   HLB numbers describe following characterestics:
•   <10 : Lipid soluble (or water-insoluble)
•   >10 : Water Soluble
•   4-8 : Antifoaming
•   7-11 : Water-in-oil emulsion
•   12-16 : Oil-in-water emulsion
•   11-14 : Good Wetting
•   12-15 : Good detergency
•   16-20 : Stabilizing
•   HLB values of fatty acid compounds are:

Polyethylene Glycol (PEG) Esters are non-toxic and non-irriting nonionic emulsifiers. They are prepared by the esterification of fatty acids with polyethylene glycols. The low molecular weight ranging PEG Esters are oil-soluble to work in nonaqueous systems. The high molecular esters are water-soluble can be used in aqueous systems. Polyethylene Glycol Esters are used as emulsifiers and in formulating emulsifer blends, thickener, resin plasticizer, emollient, opacifier, spreading agent, wetting and dispersing agent, and viscosity control agents. They also have application in the metalworking, pulp, paper, textile and as defoamers for latex paints.
NOVELUTION PEG 200 is an ethylene glycol polymer with an average molar mass of 200 g/mol. It is used as a solvent and humectant in coatings and adhesives.

Product Overview

NOVELUTION PEG 200 is a low molecular weight polyethylene glycol polymer. It combines excellent water solubility with a high degree of lubricity. NOVELUTION PEG 200 is often used as humectant in plastics and wood treatments to improve flexibility and prevent cracking. It is also used in this manner in coatings and adhesives to adjust open time. NOVELUTION PEG 200 is also used as a solvent in coatings, inks, paints, and adhesives to lower viscosity and improve freeze-thaw stability. NOVELUTION PEG 200 is also commonly used as an intermediate in the manufacture of emulsifiers and rheology modifiers.

Product Specifications

Avg. Molecular Weight: 200 g/mole
Ethylene Oxide Units: 4
Free EO, ppm: 1 max
Hydroxyl number, mg KOH/g: 534-590
Water, wt%: 0.4 max
pH, 10% in water: 4.5-7.5
Color, APhA, mg Pt/L: 20 max
Solidification Range, °C: -55 - -40
Solubility in Water @ 20 °C: Complete
Viscosity @ 20 °C, mPas: 60-70
Density @ 20 °C, g/ml: 1.124
Hygroscopicity (glycerine=100): 70
Specific Heat @ 20 °C, kJ/Kg K: 2.1
Specific Heat @ 125 °C, kJ/Kg K: 2.5

Primary Chemistry: Polyethylene Glycol
Features & Benefits
Water Soluble
Low Molecular Weight
Biodegradable
High Lubricity
Humectant
Cracking of plastic and wood caused by a loss of moisture.
Paints, coatings, adhesives and inks with not enough open time.

Compound List: Ethylene oxide (75-21-8) * This Reference Standard will be used for the identification and quantitation of Ethylene Oxide.

PEGs Dilaurate and PEGs Laurate are the diesters and monoesters, respectively, of polyethylene glycol and lauric acid used in a wide variety of cosmetic formulations as surfactans - emulsifying agents. PEG esters are produced by the ethoxylation of fatty acids. In general, ethoxylated fatty acids can contain 1,4-dioxane as a byproduct of ethoxylation. Traces of the reactants (fatty acid, ethylene oxide, and any catalysts) may remain in the finished product.

Current concentration of use data were not available; the highest previously reported concentration was 25%. The PEGs Dilaurate and PEGs Laurate are similar to the PEGs Stearate and PEGs Distearate, and to the components (Polyethylene Glycol and Lauric Acid); all of which have been addressed in previous safety assessments. PEGs were readily absorbed through damaged skin. Fatty acids such as Lauric Acid are absorbed, digested, and transported in animals and humans. The acute oral LD50 of PEG-12 Laurate was >25 g/kg in mice. In short-term feeding studies, PEGs Laurate were irritating to the gastrointestinal tract, but not necrotizing. In chronic oral toxicity studies, there was some evidence of liver damage and hyperplasia in several tissues. It is generally recognized that the PEG monomer, ethylene glycol, and certain of its monoalkyl ethers are reproductive and developmental toxins. These esters and diesters are chemically different from PEG alkyl ethers and are not expected to cause adverse reproductive or developmental effects. In actual studies, PEGs Stearate, and PEGs Distearate did not cause reproductive or developmental toxicity, and were not carcinogenic. Likewise, PEGs were not carcinogenic.

Although sensitization and nephrotoxicity were observed in burn patients treated with a PEG-based cream, no evidence of systemic toxicity or sensitization was found in studies with intact skin. Because of the possible presence of 1,4-dioxane reaction product and unreacted ethylene oxide residues, it was considered necessary to use appropriate procedures to remove these from PEGs Dilaurate and PEGs Laurate ingredients before blending them into cosmetic formulations. Based on the limited data on the PEGs Dilaurate and the PEGs Laurate, on the data available on the component ingredients, and on the data available on similar PEG fatty acid esters,it was concluded that PEG-2, -4, -6, -8, -12, -20, -32, -75, and -150 Dilaurate; PEG-2, -4, -8, -9, -10, -12, -14, -20, -32, -75, -150, and -200 Laurate; and PEG-2 Laurate SE are safe for use in cosmetics at concentrations up to 25%.

Polyethylene Glycol (PEG) Dilaurate and PEG Laurate ingredients are produced from lauric acid, a naturally occurring fatty acidin coconut oil. PEG Dilaurate and PEG Laurate ingredients are manufactured by reacting lauric acid with a specific number of units of ethylene oxide. The average number of units of ethylene oxide is indicated by the number in the ingredient name.

Chemicals Uses:

•   Because PEG is a hydrophilic molecule, it has been used to passivate microscope glass slides for avoiding non-specific sticking of proteins in single-molecule fluorescence studies.
•   Polyethylene glycol has a low toxicity and is used in a variety of products. The polymer is used as a lubricating coating for various surfaces in aqueous and non-aqueous environments
•   Since PEG is a flexible, water-soluble polymer, it can be used to create very high osmotic pressures (on the order of tens of atmospheres). It also is unlikely to have specific interactions with biological chemicals. These properties make PEG one of the most useful molecules for applying osmotic pressure in biochemistry and biomembranes experiments, in particular when using the osmotic stress technique.
•   Polyethylene glycol is also commonly used as a polar stationary phase for gas chromatography, as well as a heat transfer fluid in electronic testers.
•   PEG is often used (as an internal calibration compound) in mass spectrometry experiments, with its characteristic fragmentation pattern allowing accurate and reproducible tuning.
•   PEG derivatives, such as narrow range ethoxylates, are used as surfactants.
•   PEG has been used as the hydrophilic block of amphiphilic block copolymers used to create some polymersomes.

Biological uses

PEG can be modified and crosslinked into a hydrogel and used to mimic the extracellular matrix (ECM) environment for cell encapsulation and studies.
An example study was done using PEG-Diacrylate hydrogels to recreate vascular environments with the encapsulation of endothelial cells and macrophages. This model furthered vascular disease modeling and isolated macrophage phenotype's effect on blood vessels.
PEG is commonly used as a crowding agent in in vitro assays to mimic highly crowded cellular conditions.
PEG is commonly used as a precipitant for plasmid DNA isolation and protein crystallization. X-ray diffraction of protein crystals can reveal the atomic structure of the proteins.
Polymer segments derived from PEG polyols impart flexibility to polyurethanes for applications such as elastomeric fibers (spandex) and foam cushions.
In microbiology, PEG precipitation is used to concentrate viruses. PEG is also used to induce complete fusion (mixing of both inner and outer leaflets) in liposomes reconstituted in vitro.
Gene therapy vectors (such as viruses) can be PEG-coated to shield them from inactivation by the immune system and to de-target them from organs where they may build up and have a toxic effect.[25] The size of the PEG polymer has been shown to be important, with larger polymers achieving the best immune protection.
PEG is a component of stable nucleic acid lipid particles (SNALPs) used to package siRNA for use in vivo.
In blood banking, PEG is used as a potentiator to enhance detection of antigens and antibodies.
When working with phenol in a laboratory situation, PEG 300 can be used on phenol skin burns to deactivate any residual phenol.
In biophysics, polyethylene glycols are the molecules of choice for the functioning ion channels diameter studies, because in aqueous solutions they have a spherical shape and can block ion channel conductance.

Commercial uses:

PEG is the basis of many skin creams (as cetomacrogol) and personal lubricants (frequently combined with glycerin).
PEG is used in a number of toothpastes as a dispersant. In this application, it binds water and helps keep xanthan gum uniformly distributed throughout the toothpaste.
PEG is also under investigation for use in body armor, and in tattoos to monitor diabetes.
In low-molecular-weight formulations (e.g. PEG 400), it is used in Hewlett-Packard designjet printers as an ink solvent and lubricant for the print heads.
PEG is also used as an anti-foaming agent in food and drinks – its INS number is 1521 or E1521 in the EU.

Industrial uses:

A nitrate ester-plasticized polyethylene glycol (NEPE-75) is used in Trident II submarine-launched ballistic missile solid rocket fuel.
Dimethyl ethers of PEG are the key ingredient of Selexol, a solvent used by coal-burning, integrated gasification combined cycle (IGCC) power plants to remove carbon dioxide and hydrogen sulfide from the syngas stream.
PEG has been used as the gate insulator in an electric double-layer transistor to induce superconductivity in an insulator.
PEG is also used as a polymer host for solid polymer electrolytes. Although not yet in commercial production, many groups around the globe are engaged in research on solid polymer electrolytes involving PEG, with the aim of improving their properties, and in permitting their use in batteries, electro-chromic display systems, and other products in the future.
PEG is injected into industrial processes to reduce foaming in separation equipment.
PEG is used as a binder in the preparation of technical ceramics.

Recreational uses

PEG is used to extend the size and durability of very large soap bubbles.
PEG is the main ingredient in many personal lubricants. (Not to be confused with propylene glycol.)
PEG is the main ingredient in the paint (known as "fill") in paintballs.
Water soluble. This chemical is combustible. POLYETHYLENE GLYCOL 200 is heat-stable and inert to many chemical agents; it will not hydrolyze or deteriorate under normal conditions. This material has a solvent action on some plastics.

Use caution: Liquids with this reactive group classification have been known to react with the absorbent listed below.

Abstract

Iron oxide magnetic nanoparticles (IOMNPs) have been successfully synthesized by means of solvothermal reduction method employing polyethylene glycol (PEG200) as a solvent. The as-synthesized IOMNPs are poly-dispersed, highly crystalline, and exhibit a cubic shape. The size of IOMNPs is strongly dependent on the reaction time and the ration between the amount of magnetic precursor and PEG200 used in the synthesis method. At low magnetic precursor/PEG200 ratio, the cubic IOMNPs coexist with polyhedral IOMNPs. The structure and morphology of the IOMNPs were thoroughly investigated by using a wide range of techniques: TEM, XRD, XPS, FTIR, and RAMAN. XPS analysis showed that the IOMNPs comprise a crystalline magnetite core bearing on the outer surface functional groups from PEG200 and acetate. The presence of physisorbed PEG200 on the IOMNP surface is faintly detected through FT-IR spectroscopy. The surface of IOMNPs undergoes oxidation into maghemite as proven by RAMAN spectroscopy and the occurrence of satellite peaks in the Fe2p XP spectra.

The magnetic studies performed on powder show that the blocking temperature (TB) of IOMNPs is around 300 K displaying a coercive field in between 160 and 170 Oe. Below the TB, the field-cooled (FC) curves turn concave and describe a plateau indicating that strong magnetic dipole-dipole interactions are manifested in between IOMNPs. The specific absorption rate (SAR) values increase with decreasing nanoparticle concentrations for the IOMNPs dispersed in water. The SAR dependence on the applied magnetic field, studied up to magnetic field amplitude of 60 kA/m, presents a sigmoid shape with saturation values up to 1700 W/g. By dispersing the IOMNPs in PEG600 (liquid) and PEG1000 (solid), it was found that the SAR values decrease by 50 or 75 %, indicating that the Brownian friction within the solvent was the main contributor to the heating power of IOMNPs.

Background

In the recent decades, extensive research has been focused on the synthesis of magnetic nanoparticles (MNPs) possessing new and attractive properties that could propel them as ideal candidates for multiple biomedical applications such as contrast agents for magnetic resonance imaging , targeted drug/gene/RNA delivery , heat generators for magnetic hyperthermia , and magnetic separation and purification of biomolecular species . Among all types of magnetic nanoparticles (MNPs) developed so far, the Fe3O4 are the only type of MNPs approved for clinical use by the US Food and Drug Administration . By taking advantage of their heat-releasing capabilities as a result of their interaction with an external magnetic field, these MNPs have been recently used in several clinical trials for prostate and brain cancer treatment by means of magnetic hyperthermia ,a technique based on the higher heating sensitivity of cancer cells to heating as compared to healthy ones.
It is well know that when exposed to an external alternating magnetic field, the amount of heat released in the medium strongly depends on MNP-specific absorption rate (SAR), also called specific loss power (SLP) . Thus, SAR (which is equal to the rate at which energy is adsorbed per nanoparticles unit mass at a specific frequency) has become one of the important parameter describing MNP heating efficiency capabilities. It has been shown that SAR can by substantially raised by increasing both the frequency (f) and the amplitude (H) of the external alternating magnetic field .

Based on some physiological considerations, the maximum allowed values of the two parameters are limited in biological applications, i.e., the H × f factor should not exceed a threshold value of 5 × 109 Am−1s−1 . For human applications, the occurrence of several side effects must be taken into account above this threshold value. SAR is also strongly dependent on various intrinsic parameters of MNPs such as their size, shape, dispersity, chemical composition, surface coating, and saturation magnetization . As a consequence, it is widely accepted that by carefully controlling and tuning these properties, a substantial increase of their hyperthermia performance can be achieved.
In this scientific context, a plethora of synthetic methods, with the aim of engineering MNPs with exceptional SAR values, have been developed so far. The best Fe3O4 nanoparticles (NPs) in terms of SAR values have been synthesized using a non-hydrolytic thermal decomposition method. This technique, which consists in the thermal decomposition of magnetic precursors in organic solvents, enables the engineering of monodispersed spherical or cubical Fe3O4 NPs with single crystallinity and controlled size. Recent reports have shown that spherical Fe3O4 NPs exhibit SAR values in between 400 and 700 W/g (depending on their size) , approximately five times higher than the Feridex commercially available Fe3O4 NPs (115 W/g). Higher SAR values, up to several thousands of W/g, have been recently reported for Fe3O4 NPs exhibiting a cubic shape . As the final aim is to use these Fe3O4 nanoparticles for human clinical applications, it became compulsory to transform their hydrophobic character into a biocompatible, hydrophilic one. Different strategies have been proposed for overcoming this problem, consisting mainly in coating them with biocompatible hydrophilic molecules . Among a wide range of biopolymers employed so far, polyethylene glycol (PEG) seems to hold a great promise .

PEG is a biologically safe and degradable polymer, highly soluble in aqueous solutions preventing MNP self-aggregation and undesired adsorption of plasma proteins (opsonization) onto their surface .Since PEG does not possess groups that can bind to the nanoparticle surface, it can be chemically modified by introducing active functional groups that enable its further attachment to the nanoparticle surface. Apart from the biocompatible hydrophilic character provided upon functionalization with PEG, in a recent study, it was shown that surface coating of Fe3O4 NPs with phosphorylated methoxyPEG induces a significant increase of the SAR value. On the other hand, in order to avoid additional steps in the formation of hydrophilic MNPs, different synthesis approaches have been developed for the synthesis of MNPs exhibiting excellent water solubility.

The polyol process, based on the reduction of magnetic precursors to MNPs in liquid polyol at elevated temperatures, giving rise to monodispersed, highly crystalline, and superparamagnetic MNPs at room temperature is such an example .Among the most used classes of polyols one can find ethylene glycol, di-ethylene glycol, try-ethylene glycol, and tetra-ethylene glycol .Even though PEG of different molecular weights has been extensively used as reducing and stabilizing agent for engineering either silver or gold nanoparticles ,its capability to produce MNPs was not tested so far.
In this study, we extend the synthesis method developed by Deng et al., by replacing the ethylene glycol with PEG200 (molecular weight 200 g/mol) as solvent in a one-step synthesis method of water-soluble iron oxide magnetic nanoparticles (IOMNPs). Our approach gave rise to polydispersed F3O4 magnetic nanoparticles exhibiting cubic shape, instead of spherical shape reported by Deng et al. The average edge length can be tuned by modifying the reaction time and the amount of PEG200. The structural properties and surface composition of the IOMNPs have been thoroughly investigated by means of several complementary techniques as TEM, XRD, XPS, FT-IR, and Raman spectroscopy.

The magnetic properties investigated by VSM indicate a ferromagnetic behavior of IOMNPs at room temperature pointing out a strong dipole-dipole inter-particle interaction, leading to their aggregation in water. Despite this, the heating rate of IOMNPs in water (0.5 mg/ml) at H × f factors close to biological limit reaches values between 910 and 1700 W/g.

Methods

All the reagents employed in this study were of analytical grade and were used without any further purification. The synthesis of magnetic nanoparticles has been performed with the following products: iron(III) chloride hexahydrate (FeCl3 6H2O) (Roth, ≥98 %), polyethylene glycol 200 (PEG200) (Roth, ≥99 %), and sodium acetate trihydrate (NaAc) (Roth, ≥99.5 %).
The general synthetic procedure for the preparation of iron oxide magnetic nanoparticles was as follows: FeCl3 6H2O (0.675 g) and sodium acetate (NaAc) (1.8 g) were mixed and dissolved in either 60 or 90 ml of PEG200. The solutions were stirred thoroughly at room temperature for 30 min, transferred in sealed glass bottles, and heated at 240 °C for 6, 8, 10, and 12 h. The final temperature was reached at heating rates of 43 and 5 °C/min.

The glass bottles were let to cool at room temperature, the excess liquid was discharged, and the obtained black precipitates were washed with ethanol, several times, in order to remove the excess of ligands and unreacted precursors. Finally, the black precipitates were dispersed and kept in double distilled water for further analysis.
TEM images were taken on a Jeol JEM 1010 transmission electron microscope (Jeol Ltd., Tokyo, Japan), equipped with a Mega VIEW III camera (Olympus, Soft Imaging System, Münster, Germany), operating at 80 kV. For TEM examination, 5-μl drops of each solution were deposited on carbon-coated copper grids. After 1 min, the excess water was removed by filter paper and the samples were left to dry under ambient air.
X-ray diffraction (XRD) measurements were carried out on powder samples at room temperature on a Bruker D8 Advance diffractometer using Cu Kα radiation. The lattice parameters and phase percentages were calculated using the FullProf software.
XPS measurements were performed with a SPECS PHOIBOS 150 MCD instrument, equipped with monochromatized Al Kα radiation (1486.69 eV) at 14 kV and 20 mA and a pressure lower than 10−9 mbar. The binding energy scale was charge referenced to the C1s photoelectron peak at 285 eV. A low energy electron flood gun was used for all measurements to minimize sample charging. The elemental composition on the outermost layer of samples (about 5 nm deep from surface) was estimated from the areas of the characteristic photoelectron lines in the survey spectra assuming a Shirley type background. High-resolution spectra were recorded in steps of 0.05 eV using analyzer pass energy of 30 eV. The spectra deconvolution was accomplished with Casa XPS (Casa Software Ltd., UK).
The mid-infrared spectrum of powder IOMNPs, sodium acetate, and PEG200 was recorded on a Jasco 4000 FTIR spectrometer in attenuated total reflectance (ATR) mode using a one reflection ATR accessory with ZnSe crystal. The detection system consisted in a DTGS detector, the spectral resolution of the recorded FT-IR spectrum being 4 cm−1.
Raman measurements were recorded using a multilaser confocal Renishaw InVia Reflex Raman spectrometer. The wavelength calibration was performed by using a silicon waver buffer. The 633-nm laser line of a He–Ne laser was employed as the excitation source. The Raman spectra were recorded on powder deposited on aluminum-covered glass, with a 50× objective and an acquisition time of 10–20 s, while the emitting laser power was varied between 15 mW and maximum value of 150 mW. The spectral resolution of the spectrometer was 0.5 cm−1.
Dynamic light scattering (DLS) measurements were taken using a Zetasizer Nano ZS90 (Malvern Instruments, Worcestershire, UK) in a 90° configuration. One cycle of 30 measurements was performed for each sample.
Magnetic measurements were performed on powder samples in the 4–300 K temperature range in external applied fields up to 2 T, using a vibrating sample magnetometer (VSM) produced by Cryogenic Limited.
Hyperthermia measurements were recorded with a magnetic heating system Easy Heat 0224 provided by Ambrell (Scottsville, NY, USA). The samples, usually 0.5 ml of IOMNP suspensions at different concentrations were placed in a thermally insulated vial, at the center of an 8-turn coil, connected to the remote heat station of the device. With this setup, alternating magnetic fields with strengths up to 65 kA/m and frequencies between 100 and 400 kHz were generated in the center of the coil.

The temperature was measured using a fiber-optic probe, placed in the center of the vial, connected to a computer, providing the temperature values each second. The calibration of the setup, the recording protocol of temperature change versus time, and the SAR calculation are briefly described in the “Additional File”.

Results and Discussion

Structural Characterization of IOMNPs
As it was mentioned above, polyethylene glycol (PEG) was not tested so far as a reducing agent in the synthesis of MNPs. In this paper, the reduction reaction of FeCl3 by PEG200 in the presence of sodium acetate, in a solvothermal system, has been performed for several magnetic precursors/PEG200 ratios. In this regard, we have fixed the amount of magnetic precursor to 0.675 g while the volume of PEG200 was gradually increased from 10 to 120 ml. It was observed that for PEG200 volumes lower than 60 ml, the IOMNPs cannot be synthesized. The formation of IOMNPs starts for 60 ml of PEG200. TEM size analysis indicates that IOMNPs, synthesized in 60 ml of PEG200 at 240 °C for 6 h, have a cubic shape and are poly-dispersed with a broad edge length distribution; the mean edge length being 128 nm. The cubic shape of the IOMNPs is preserved if the temperature rate used to reach the final reaction temperature of 240 °C was diminished to 5 °C/min . In this case, the mean edge length of the cubic IOMNPs increases to 139 nm. Based on previously reported results, it is believed that a low heating rate promotes nucleation at lower temperatures thus enabling the formation of a few seeds. Once formed, the seeds will further prevent further nucleation at high temperatures by quickly consuming monomers and thus developing larger nanoparticles. The cubic edge lengths of the poly-dispersed IOMNPs are further increased as the reaction time at 240 °C is longer than 6 h. No important changes were observed for reaction time of 8 or 10 h. A significant increase in the mean cubic edge lengths of the poly-dispersed cubic IOMNPs to 230 nm was observed starting with a reaction time of 12 h
Furthermore, the PEG200 volume was increased to 90 ml while keeping unchanged the reaction condition. In this case, the TEM images exhibited the coexistence of poly-dispersed cubic and polyhedral IOMNPs with lower dimensions. As expected, the size of IOMNPs gradually increased with the reaction time. For instance, for a reaction time of 6 h at 240 °C, the IOMNPs have a mean size of 30 nm, whereas for 12 h, the mean size increases around 48 nm. No significant changes in the morphology and size were observed when the PEG200 volume was further increased to 120 ml. It is worth noting that we could not increase the reaction temperatures above 240 °C as PEG200 starts to boil. Also, below 240 °C, the nanoparticle synthesis cannot be performed. At the same time, for a reaction temperature of 240 °C, the synthesis can be completed only for reaction times longer than 6 h. Consequently, the formation of IOMNPs in the proposed solvothermal system, employing PEG200 as reducing agent, requires at least 60 ml of PEG200, a temperature of 240 °C, and a reaction time of minimum 6 h. The samples were also analyzed by DLS and the hydrodynamic diameters of the IOMNPs were found between 400 and 800 nm, indicating that IOMNPs aggregate in aqueous solutions although the samples were treated with tetramethylammonium hydroxide (TMAOH) as discussed below. Thus, the application of DLS for further characterizing both the size and shape of IOMNPs is limited.
The water solubility of cubic IOMNPs synthesized by means of laborious non-hydrolytic methods can be achieved through an additional step based on ligand exchange reaction as it was previously reported. The herein presented procedure allows—in a one-step process—the synthesis of water-soluble cubic IOMNPs in a very rapid and facile manner using PEG200 as reducing agent. Moreover, by taking into account that polyols used in the polyol-mediated synthesis enabled the preparation of high-quality water stable IOMNPs having a spherical shape, one can suppose that PEG200 acts also as a shape-directing agent, thus giving rise to either cubic or polyhedral IOMNPs. The variation of IOMNP shape upon the increase of the amount of PEG200 may rely on the ratio of magnetic precursor/surfactant. Since the selective adsorption of surfactant on a particular surface is dependent on surface energy and the high-index crystallography planes possess higher surface energy, the IOMNPs will tend to be surrounded by low-index planes, such as the, and planes. Based on previous studies on the growth mechanism of different MNPs in the presence of oleic acid, it can be speculated that PEG200 will tend to accumulate on the (110) surface, inducing a faster growth in the direction and thus leading to the formation of cubic IOMNPs. When the amount of PEG200 is increased, there will be a competing growth in both the and directions, resulting in the formation of polyhedral IOMNPs.
Typical XRD patterns of IOMNPs synthesized in either 60 of 90 ml of PEG200 for 6, 8, 10, and 12 h taken at room temperature are presented in. In the case of IOMNPs prepared in 60 ml of PEG200, the XRD patterns reveal the coexistence of two phases. The position and the relative intensities of the diffraction peaks ascribe the two phases to magnetite Fe3O4 and hematite α-Fe2O3 . Since the mean size of the nanoparticles is greater than 100 nm, all diffraction peaks existing in the XRD patters are sharp. The corresponding lattice parameters for the four samples are listed in Additional file 1: Table S1 and are very closed to those of bulk samples (a = 8.375 Å for Fe3O4 and a = 5.037 Å, c = 13.771 Å for α-Fe2O3). In Additional file 1: Table S1, the percentage concentrations of both crystalline phases (Fe3O4 and α-Fe2O3) are calculated based on our experimental XRD data. It can be observed that the concentration of hematite is very low compared with that of magnetite and varies randomly as a function of the reaction time.

The nanoparticles prepared in 90 ml of PEG200 showed an improved crystallinity as it was demonstrated by the position and the relative intensities of their diffraction peaks, matching well with the standard XRD data for bulk magnetite. Moreover, no peaks of any other phases are observed, indicating the high purity of the products. The black color of the powders can be considered a further confirmation of the fact that samples contain mainly magnetite phase and not maghemite (brown), possessing the same spinel structure and very similar XRD pattern. The lattice parameters for these samples are close to those of bulk material. The formation of an additional hematite phase for the samples synthesized using 60 ml of PEG200 may be explained by the transformation of a part of the spinel structured iron oxide under oxidative conditions. It has been observed that the addition of PEG200 in a larger quantity (synthesis performed using 90 ml of PEG200) prevents the formation of the hematite phase and reduces the oxidation degree of the spinel structure, as it was previously reported.

The Surface Composition of IOMNPs
X-ray photoelectron spectroscopy (XPS) is a surface-sensitive technique, probing the outermost 5–10 nm of the MNPs. Figure 4 shows the Fe2p, O1s, and C1s XP spectra of the IOMNPs synthesized in 60 and 90 ml of PEG200. The Fe2p XPS spectra of all analyzed samples are similar with that of macro-scaled crystalline Fe3O4 . The Fe2p spectra have been deconvoluted according to the procedure presented in , and consequently each region (Fe2p1/2 and Fe2p3/2) can be deconvoluted to the sum of five peaks. For the Fe2p3/2 region, the lowest binding energy peak at 709.4 eV is attributed to Fe2+ octahedral species, which has a corresponding satellite at 714.4 eV. The Fe3+ octahedral and tetrahedral species are found at binding energies of 710.5 and 711.8 eV, while their satellite is located at 718.6 eV. According to and , very small MNPs (around 10 nm) induce a weak satellite structure in the XPS spectra. In our case, the observed satellite peaks are more intense than those reported in previous studies and the Fe2+ and Fe3+ shake-up features can be easily resolved, proving that IOMNPs size is larger than 100 nm as it was further confirmed by our TEM and XRD analysis. For the samples prepared in 90 ml of PEG200, the satellite peaks are significantly reduced indicating that the corresponding Fe3O4 MNPs exhibit a smaller size compared to their counterparts prepared in 60 ml of PEG200. This observation is also reasonably supported by the TEM images. The peak located at very low binding energy (704.6 eV) is an instrumental artifact. The Fe2+/Fe3+ ratio for samples prepared in either 60 or 90 ml of PEG200 is close to the predicted value of 0.5 expected from the stoichiometry of Fe3O4. Nevertheless, the satellite peaks in the Fe2p XPS spectra of all samples suggest that the surface of IOMNPs is partially oxidized.
In order to clarify this issue, a detailed analysis of the O1s and C1s spectra was accomplished. The deconvolution of the O1s and C1s XPS regions provide information related to the chemical environment changes of the elements present on the surface of IOMNPs. As can be seen in the XPS profile of O1s electrons can be decomposed in three peaks corresponding to oxygen in three different environments. According to the literature, they can be attributed as follows: 528.7 eV—oxygen in the Fe-O (lattice oxygen) component of magnetite; 530 eV—oxygen in an O-H, O-C, and O = C components; and 521.6 eV—oxygen in the bidentate bond of carboxylate moiety O-C = O. The deconvolution of C1s XP spectra reveals the existence of three peaks which, according to the literature, can be assigned to the following: aliphatic or alkyl carbon at 285 eV, carbon single bonded to oxygen at 286.6 eV and carbon double bound to O or from carboxylate moiety (-O-C = O) at 288.6 eV, respectively. The XP spectra of the other samples (8 and 10 h), not shown here, are similar to those presented in Fig. 4.
While the nature of the most intense peak in the O1s XP spectra is rather clear, the origin of the chemical species that give rise to additional peaks in both O1s and C1s XPS spectra can be identified taking into account the possible reaction mechanisms that occurs in our system. Besides being used as a buffer, the acetate groups also stabilize the IOMNPs as they form. Therefore, the signals at 531.6 eV in O1s and 288.6 eV in C1s are most likely due to these acetate groups from the IOMNP surface. The hydrolysis of magnetic precursor FeCl3 (water is present in the reaction system as a part of the added salts, which are found only in the form of crystalohydrates) leads to the occurrence of Fe(OH)3 and HCl, which is neutralized by sodium acetate, resulting CH3COO- that binds to the surface of IOMNPS through the two oxygen atoms giving rise to the peaks at 532.1 and 288.2 eV in XP spectra of O1s and C1s electrons. Due to the high temperature, a fraction of Fe(OH)3 will dehydrate to form Fe2O3, while the rest of Fe(OH)3 will interact with PEG200, under the influence of which the Fe3+ ion is reduced to Fe2+. The C-C, C-O, and C = O components of physisorbed PEG200 and the C-H3 group of acetate attached to the IOMNP surface are identified in XP spectra by the O1s peak at 531.5 eV and C1s peaks at 285, 286.6, and 288.7 eV. For the samples prepared in 90 ml of PEG200, the Fe content at the surface (Additional file 1: Table S4) decreases while the amount of C increases compared with the samples prepared in 60 ml of PEG200. As a consequence, the C1s peak at 286.6 eV corresponding to C-O dominates the C1s XPS spectrum
Further evidence for the presence of different molecular species on the surface of IOMNPs is obtained from FT-IR spectroscopy. Figure shows the FT-IR spectra of IOMNPs obtained in 60 and 90 ml of PEG200 for a reaction time of 12 h together with the FT-IR spectra of PEG200 and sodium acetate. The FT-IR spectra of IOMNPs are dominated by a strong absorption band around 540 cm−1, which can be ascribed to Fe-O bond in Fe3O4 nanoparticles, indicating that the main phase of the as-synthesized IOMNPs is Fe3O4. In 650–1450 cm−1 region, the FT-IR spectrum of PEG200 is characterized by several absorption bands. The most intense absorption band in this region, located at 1062 cm−1, attributed to vibration band of C-O bond, is the only absorption band of PEG200 which is faintly visible in the FT-IR spectra of IOMNPS. Similarly, the stretching vibrations of the carboxyl salt of the sodium acetate, located between 1300 and 1700 cm−1, are also feebly present in the FT-IR spectra of IOMNPs. These experimental observations suggest that very small amounts of PEG200 and acetate are present onto the surface of IOMNPs. These findings, combined with those obtained by XPS, support the assumption of a partial oxidation of IOMNPs surface.
In order to verify the oxidation degree of IOMNPs, we have analyzed the IOMNPs by means of Raman spectroscopy. This technique has emerged as a powerful tool for the investigation of oxide nanostructures, being capable to discern between different phases of IOMNPs. As it can be seen in Fig. 5b (spectrum a), the Raman spectrum acquired on IOMNP powder exhibits peaks around 374, 497, and 708 cm−1. The relative positions of the peaks and the overall shape of the spectrum resemble to that of maghemite, which was obtained by annealing the magnetite powder at 250 °C for 4 h. Note that, upon annealing, the color of the magnetic powder has changed from black to brown, which is characteristic to maghemite phase. The further annealing of the magnetite powder at 550 °C for 6 h induces the formation of hematite. The spectrum e in Fig. 5b clearly exhibits the characteristic vibrational modes of hematite. Moreover, the transformation of magnetite into hematite can also be induced by the excitation laser of the Raman spectrometer. Increasing the laser power to its maximum value (150 mW) and the integration time to 20 s leads to the occurrence of different peaks corresponding to hematite phas. For instance, the apparition of a second-order longitudinal phonon mode around 1300 cm−1 a feature characteristic to hematite phase confirms the conversion of magnetite intro hematite upon laser excitation. The same laser treatment applied to maghemite powder gives rise to the occurrence of two peaks of low intensity at small wavenumbers characteristic to hematite phases, whereas the three peaks of maghemite are better resolved. Since the maghemite phase is much more stable than magnetite, one can believe that a complete conversion into hematite will require higher energy. It can be thus concluded that IOMNPs are Fe3O4 whose surface is oxidized in maghemite.
Magnetic Properties of IOMNPs