**1. Introduction**

148 Materials Science and Technology

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Biomedical Polymer-Silicate Nanocomposites: A Materials Science Perspective.

Magnetic particles have a significant role in nanotechnology due to their surface properties and their applicability in physical and chemical processes like ionic exchange, specific complexation, biocompatibility and bioactivity, capacity of selection and transport for cells and chemical compounds (Safarik & Safarikova, 2002).

Magnetite is an interesting superparamagnetic nanomaterial, considered as a challenge by the modern research related magnetic applications, due to its high susceptibility at oxidation as compared to other magnetic compounds (Cornell & Schwertmann, 1996).

The name "superparamagnetic" refers to those particles that in presence of magnetic field are attracted and in absence of the magnetic field the particles don't have residual magnetism. The importance of magnetite particles is related to their most important properties - magnetic and catalytic. These properties are strongly dependent on the selected method of preparation.

These magnetic particles are used in many applications that involve their immobilization and transport in the presence of magnetic field, or magnetically tagged biological entities due to the intrinsic penetrability of magnetic fields into human tissue.

The chapter describes the most important approaches in the preparation of magnetite particles, as presented in the literature. An introspective view of biomedical, industrial and catalytic applications of magnetite micro- and nanoparticles is also reported.

The magnetite particles are usually attracted to each other. Electrostatic or steric stabilization represent the main step in obtaining "core-shell" magnetic particles with magnetite core and a shell formed by different surfactants. We summarize here some examples and also some data previously reported by our group (figure 1) on the preparation of magnetite particles coated by different Si-containing compounds (monomers and polymers) (Durdureanu-Angheluta et al., 2008; Durdureanu-Angheluta et al., 2009; Durdureanu-Angheluta et al., 2010; Pricop et al., 2010).

Tailored and Functionalized Magnetite Particles for Biomedical and Industrial Applications 151

 2FeCl3 + FeCl2 + 8NH3 + 4H2O → Fe3O4 + 8NH4Cl (1) The disadvantage of the co-precipitation process is that the control of particle size distribution is limited, due to kinetic factors that are controlling the growth of the crystal. Two stages are involved in the co-precipitation process (Cornell & Schwertmann, 1996; Boistelle et al., 1988; Sugimoto, 2003; Cornell et al., 1991; Gribanow et al., 1990): nucleation that occurs when the concentration of the species reaches critical supersaturation, and a slow growth of the nuclei by diffusion of the solutes to the surface of the crystal. To produce monodisperse iron oxide nanoparticles, these two stages should be separated. Nucleation

An alternative route to obtain magnetite particles by co-precipitation is the method described by Kim et al. (Kim et al., 2001) and Koneracka et al. (Koneracka et al., 2002) involving the preparation of the two solutions of ferric chloride (FeCl3•6H2O) and ferrous sulphate (FeSO4) by dissolution in a HCl solution at room temperature under vigorous stirring using a mechanical stirrer. The solutions are mixed and an aqueous dispersion of particles is obtained after adding a solution of NaOH under sonication or under vigorous

Magnetic particles are prepared, also, using FeCl3•6H2O and FeSO4•7H2O salts in aqueous solutions, both added in a polymeric starch matrix at 800C under nitrogen atmosphere and vigorous stirring (Jiang et al., 2009). NaOH should be added to the mixture until reaching a

The reaction takes place at the water/oil interface. An aqueous solution containing Fe2+/Fe3+ salts is added to an organic solvent containing the stabilizer. The sol-gel reaction is performed at room temperature and is based on the hydroxylation and condensation of molecular precursors in solution and leads to a three-dimensional metal oxide network, the wet gel. Heat treatments are further needed to acquire the final crystalline state (Liu et al., 1997; Kojima et al., 1997). The properties of the gel are dependent on the structure created

Sol-gel nanocomposite materials (FexOy-SiO2) were obtained using alkoxide and aqueous routes (Raileanu et al., 2003). The structure and properties of the prepared particles were compared for different precursors of silica (tetramethoxysilane, methyltriethoxysilane,

Magnetite-based ferrofluids were synthesized through a modified sol–gel method (Gamarra et al., 2005). They precipitated iron oxyhydroxy in water in the presence of a surfactant (Renex), and next they partiallly reduced Fe3+ to Fe2+ by a mild drying process in N2

and H-, respectively, giving an

contact with a neutral aqueous solution is able to adsorb OH-

should be avoided during the period of growth (Tartaj et al., 2006).

basic pH (9-11) and the black precipitate is neutralized with HCl.

mechanical stirring.

**2.2 Sol-gel reaction** 

during the sol stage of the sol-gel process.

atmosphere, leading to the formation of magnetite.

colloidal silica solution, etc.).

OH- rich surface (Durdureanu-Angheluta et al., 2008). The reaction for obtaining magnetite is given below:

Fig. 1. Schematic representation of the preparation of core-shell magnetite particles with different Si-containing compounds.

#### **2. Synthesis methods**

Magnetite particles are quite intriguing, due to their catalytic and magnetic properties strongly dependent on the chosen synthesis method. Several methods are described in the literature, but in the present manuscript we are going to focus on the most common ones: iron salts co-precipitation (Massart, 1981; Martinez-Mera et al., 2007), sol-gel reaction, microemulsion (Woo et al., 2003), reaction in mass without solvent (Ye et al., 2006), polyols process (Feldmann & Jungk, 2001), decomposition of iron pentacarbonyl (Shafi et al., 2001), etc.

#### **2.1 Co-precipitation**

The synthesis by co-precipitation is the easiest way to obtain iron oxides like magnetite (Fe3O4) (Laurent et al., 2008) or like maghemite (γ-Fe2O3) and has shown to be a highly economic and versatile method. We used the method described by Massart (Massart, 1981) involving the co-precipitation of two iron salts FeCl3•6H2O and FeCl2•4H2O, both prepared in HCl, with the consequent addition of a NH4OH solution, vigorous stirring and under anoxic conditions, at room temperature. The shift of the initially orange color of the solution to black indicates the formation of magnetite particles. The surface of magnetite particles, in contact with a neutral aqueous solution is able to adsorb OH and H-, respectively, giving an OH- rich surface (Durdureanu-Angheluta et al., 2008).

The reaction for obtaining magnetite is given below:

$$2\text{FeCl}\_3 + \text{FeCl}\_2 + 8\text{NH}\_3 + 4\text{H}\_2\text{O} \rightarrow \text{Fe}\_3\text{O}\_4 + 8\text{NH}\_4\text{Cl} \tag{1}$$

The disadvantage of the co-precipitation process is that the control of particle size distribution is limited, due to kinetic factors that are controlling the growth of the crystal. Two stages are involved in the co-precipitation process (Cornell & Schwertmann, 1996; Boistelle et al., 1988; Sugimoto, 2003; Cornell et al., 1991; Gribanow et al., 1990): nucleation that occurs when the concentration of the species reaches critical supersaturation, and a slow growth of the nuclei by diffusion of the solutes to the surface of the crystal. To produce monodisperse iron oxide nanoparticles, these two stages should be separated. Nucleation should be avoided during the period of growth (Tartaj et al., 2006).

An alternative route to obtain magnetite particles by co-precipitation is the method described by Kim et al. (Kim et al., 2001) and Koneracka et al. (Koneracka et al., 2002) involving the preparation of the two solutions of ferric chloride (FeCl3•6H2O) and ferrous sulphate (FeSO4) by dissolution in a HCl solution at room temperature under vigorous stirring using a mechanical stirrer. The solutions are mixed and an aqueous dispersion of particles is obtained after adding a solution of NaOH under sonication or under vigorous mechanical stirring.

Magnetic particles are prepared, also, using FeCl3•6H2O and FeSO4•7H2O salts in aqueous solutions, both added in a polymeric starch matrix at 800C under nitrogen atmosphere and vigorous stirring (Jiang et al., 2009). NaOH should be added to the mixture until reaching a basic pH (9-11) and the black precipitate is neutralized with HCl.

### **2.2 Sol-gel reaction**

150 Materials Science and Technology

Fig. 1. Schematic representation of the preparation of core-shell magnetite particles with

Magnetite particles are quite intriguing, due to their catalytic and magnetic properties strongly dependent on the chosen synthesis method. Several methods are described in the literature, but in the present manuscript we are going to focus on the most common ones: iron salts co-precipitation (Massart, 1981; Martinez-Mera et al., 2007), sol-gel reaction, microemulsion (Woo et al., 2003), reaction in mass without solvent (Ye et al., 2006), polyols process (Feldmann & Jungk, 2001), decomposition of iron pentacarbonyl (Shafi et al., 2001),

The synthesis by co-precipitation is the easiest way to obtain iron oxides like magnetite (Fe3O4) (Laurent et al., 2008) or like maghemite (γ-Fe2O3) and has shown to be a highly economic and versatile method. We used the method described by Massart (Massart, 1981) involving the co-precipitation of two iron salts FeCl3•6H2O and FeCl2•4H2O, both prepared in HCl, with the consequent addition of a NH4OH solution, vigorous stirring and under anoxic conditions, at room temperature. The shift of the initially orange color of the solution to black indicates the formation of magnetite particles. The surface of magnetite particles, in

different Si-containing compounds.

**2. Synthesis methods** 

**2.1 Co-precipitation** 

etc.

The reaction takes place at the water/oil interface. An aqueous solution containing Fe2+/Fe3+ salts is added to an organic solvent containing the stabilizer. The sol-gel reaction is performed at room temperature and is based on the hydroxylation and condensation of molecular precursors in solution and leads to a three-dimensional metal oxide network, the wet gel. Heat treatments are further needed to acquire the final crystalline state (Liu et al., 1997; Kojima et al., 1997). The properties of the gel are dependent on the structure created during the sol stage of the sol-gel process.

Sol-gel nanocomposite materials (FexOy-SiO2) were obtained using alkoxide and aqueous routes (Raileanu et al., 2003). The structure and properties of the prepared particles were compared for different precursors of silica (tetramethoxysilane, methyltriethoxysilane, colloidal silica solution, etc.).

Magnetite-based ferrofluids were synthesized through a modified sol–gel method (Gamarra et al., 2005). They precipitated iron oxyhydroxy in water in the presence of a surfactant (Renex), and next they partiallly reduced Fe3+ to Fe2+ by a mild drying process in N2 atmosphere, leading to the formation of magnetite.

Tailored and Functionalized Magnetite Particles for Biomedical and Industrial Applications 153

Magnetite/silica particles were prepared by reverse-micelle micro-emulsions in an organic

Fe3O4 nanoparticles in poly(organosilsesquioxane) with sizes of 4-15 nm were prepared by the one-pot synthesis using reverse micelle method (Ervithayasuporn et al., 2009). The ferrofluid droplets were in situ encapsulated, via polycondensation of molecularly self-

Magnetite nanoparticles were obtained by a sonochemical micro-emulsion polymerization process of n-butyl methacrylate (BMA) monomer (Teo et al., 2009). Iron tri(acetylacetonate), 1,2-tetradecanediol, oleic acid, and oleyl amine were mixed in benzyl ether, under vigorous stirring. The mixture was heated gradually under nitrogen atmosphere and the blackcolored mixture was then cooled to room temperature by removing the heat source. The pre-formed particles were then encapsulated within the host poly(BMA) latex particles with 120 nm diameter and low size dispersion. The distribution of magnetite particles over the polymer particle population and within each polymer particle was nevertheless rather heterogeneous and the ratio of magnetite particles per polymer particle was determined as

The stoechiometric factor of Fe2+ and Fe3+ is important for the magnetic properties of the obtained particles (coercivity, crystallinity, sorbtion capacity, etc.) (Gorski et al., 2010). The Fe2+ chemical species direct the magnetite particles synthesis kinetics and their composition (Tronc et al., 1992). The Fe2+/Fe3+ molar ratio is highly important if one focusses on obtaining magnetite particles with specific properties. Thus, a Fe2+/Fe3+<0.l molar ratio is too small to achieve a stable solution. In this context, if the content of chemical species of Fe2+ is low, goethite (α-FeO(OH)) is obtained as the only stable product. The use of the

The influence of the Fe2+/Fe3+ molar ratio on the characteristics of magnetite particles obtained by co-precipitation of Fe2+ and Fe3+ (composition, size, morphology and magnetic properties) was studied by Jolivet (Jolivet et al., 1992). Chemical species in different proportions were precipitated with ammonia solution to pH~11. The analysis of the products obtained with different Fe2+/Fe3+ molar ratios, in the range 0.10-0.50, concluded

(a) the first phase contains particles of 4 nm in diameter, with oxyhydroxy (FeO(OH))

(b) the second phase is characterized by increased content of Fe2+ (Fe2+/Fe3+~0.33 molar ratio), the final product is magnetite with increased particle sizes. It was noticed that the share of this phase increases with increasing the Fe2+/Fe3+ molar ratio. Thus, for values

In conclusion, for a 0.5 Fe2+/Fe3+ molar ratio homogenous magnetite particles of uniform size and composition are more likely to be obtained. The order of addition of ionic species (Fe2+ and Fe3+) in co-precipitation reaction does not influence the final characteristics (size,

surface functional groups and low Fe2+ content, reflected by the ratio Fe2+/Fe3+~0.07;

Fe2+/Fe3+>0.1 molar ratio is favorable for obtaining magnetite instead of goethite.

phase such as cyclohexane and heptane (Yang et al., 2004; Santra et al., 2001).

assembled octenyltrimethoxysilane.

being equal to 50.

**Sonochemical decomposition of iron pentacarbonyl** 

**3. Influence of Fe2+ onto magnetite properties** 

that for values lower than 0.30 two different phases coexist:

greater than 0.35, the product is found only in the second phase.

composition) of the obtained particles.

#### **2.3 Free-solvent synthesis**

The free-solvent synthesis of magnetite is an economical and non-toxic method. The solid iron salts (FeCl3•6H2O and FeCl2•4H2O) and a solid base (NaOH) are used directly with the surfactant and mixed together using a mortar and a pestle (Ye et al., 2006). The synthesis procedure takes place at room temperature in a glove box filled with argon gas. This method is easy, without any advanced techniques and toxic solvents. The reaction duration is about a few minutes and the high yield magnetite obtained is monodisperse.

### **2.4 Other methods**

#### **Polyol process**

Polyols are known to reduce metal salts to metal particles and to be good solvents for various inorganic compounds. This is why the synthesis of nano- and microparticles with well-defined shapes and controlled sizes can be performed by the polyol process, also ( Fievet et al., 1989). The metal precursor is heated to a given temperature which cannot be higher than the boiling point of the polyols, with generation of intermediates that are reduced to metal nuclei and nucleate to form metal particles. Polyols act like solvents due to their high dielectric constants and like surfactants, preventing the particles aggregation. Their high boiling points offer the advantages of operating on a large temperature interval (from 250C up to the boiling point). The "core-shell" PVP (poly(vinylpyrrolidone)) nanoparticles can be obtained in one-pot polyol process by reduction of Fe(acac)3 with 1,2 hexadecanediol in the presence of the PVP polymer surfactant in octyl ether (Liu et al., 2007). These particles are promising for biomedical applications like MRI agents and biosensors. The magnetite nanoparticles prepared by this method have a long-term stability and are easily coated by various materials to generate multifunctional nanoparticles. Nonaggregated magnetite nanoparticles have been already synthesized in liquid polyols at elevated temperature (Cai et al., 2007). Highly performance magnetite nanoparticles have been also obtained by a modified polyol process. For that, only one iron rich precursor has been used and no further reducing agent and surfactants were required. The magnetite nanoparticles can be coated in situ by hydrophilic polyol ligands, and the hydrophilic triethylene glycol magnetic nanoparticles are easily dispersed in water and other polar solvents. This method is a good alternative to produce superparamagnetic water-soluble magnetic nanoparticles and can replace the co-precipitation method.

#### **Micro-emulsion**

Emulsions are thermodynamically stable and consist of two different immiscible liquids (like oil - organic solvent and water) (Bagwe et al., 2001). The emulsion is stabilized by adding a surfactant. The size of magnetite particles synthesized by micro-emulsion method is several nanometers in diameter (López Pérez et al., 1997), except in some specific cases (20-30 nm) (Hirai et al., 1997). This method is difficult to control, the obtained yield is low and the particles are polydisperse. The commonly used method is the one that involves water-in-oil micro-emulsion and also includes a reverse micelle system (Ganguli et al., 2003). For the synthesis of Fe3O4, the precipitation technique consisting of alkalization of a solution of metal salt and hydrolysis in micro-emulsions (Boal et al., 2004; Hirai et al., 1997) is commonly used, as well as biosynthetic routes (Matsunaga, 1998).

Magnetite/silica particles were prepared by reverse-micelle micro-emulsions in an organic phase such as cyclohexane and heptane (Yang et al., 2004; Santra et al., 2001).

Fe3O4 nanoparticles in poly(organosilsesquioxane) with sizes of 4-15 nm were prepared by the one-pot synthesis using reverse micelle method (Ervithayasuporn et al., 2009). The ferrofluid droplets were in situ encapsulated, via polycondensation of molecularly selfassembled octenyltrimethoxysilane.

#### **Sonochemical decomposition of iron pentacarbonyl**

152 Materials Science and Technology

The free-solvent synthesis of magnetite is an economical and non-toxic method. The solid iron salts (FeCl3•6H2O and FeCl2•4H2O) and a solid base (NaOH) are used directly with the surfactant and mixed together using a mortar and a pestle (Ye et al., 2006). The synthesis procedure takes place at room temperature in a glove box filled with argon gas. This method is easy, without any advanced techniques and toxic solvents. The reaction duration

Polyols are known to reduce metal salts to metal particles and to be good solvents for various inorganic compounds. This is why the synthesis of nano- and microparticles with well-defined shapes and controlled sizes can be performed by the polyol process, also

Fievet et al., 1989). The metal precursor is heated to a given temperature which cannot be higher than the boiling point of the polyols, with generation of intermediates that are reduced to metal nuclei and nucleate to form metal particles. Polyols act like solvents due to their high dielectric constants and like surfactants, preventing the particles aggregation. Their high boiling points offer the advantages of operating on a large temperature interval (from 250C up to the boiling point). The "core-shell" PVP (poly(vinylpyrrolidone)) nanoparticles can be obtained in one-pot polyol process by reduction of Fe(acac)3 with 1,2 hexadecanediol in the presence of the PVP polymer surfactant in octyl ether (Liu et al., 2007). These particles are promising for biomedical applications like MRI agents and biosensors. The magnetite nanoparticles prepared by this method have a long-term stability and are easily coated by various materials to generate multifunctional nanoparticles. Nonaggregated magnetite nanoparticles have been already synthesized in liquid polyols at elevated temperature (Cai et al., 2007). Highly performance magnetite nanoparticles have been also obtained by a modified polyol process. For that, only one iron rich precursor has been used and no further reducing agent and surfactants were required. The magnetite nanoparticles can be coated in situ by hydrophilic polyol ligands, and the hydrophilic triethylene glycol magnetic nanoparticles are easily dispersed in water and other polar solvents. This method is a good alternative to produce superparamagnetic water-soluble

Emulsions are thermodynamically stable and consist of two different immiscible liquids (like oil - organic solvent and water) (Bagwe et al., 2001). The emulsion is stabilized by adding a surfactant. The size of magnetite particles synthesized by micro-emulsion method is several nanometers in diameter (López Pérez et al., 1997), except in some specific cases (20-30 nm) (Hirai et al., 1997). This method is difficult to control, the obtained yield is low and the particles are polydisperse. The commonly used method is the one that involves water-in-oil micro-emulsion and also includes a reverse micelle system (Ganguli et al., 2003). For the synthesis of Fe3O4, the precipitation technique consisting of alkalization of a solution of metal salt and hydrolysis in micro-emulsions (Boal et al., 2004; Hirai et al., 1997) is

is about a few minutes and the high yield magnetite obtained is monodisperse.

magnetic nanoparticles and can replace the co-precipitation method.

commonly used, as well as biosynthetic routes (Matsunaga, 1998).

**2.3 Free-solvent synthesis** 

**2.4 Other methods** 

**Polyol process** 

**Micro-emulsion** 

(

Magnetite nanoparticles were obtained by a sonochemical micro-emulsion polymerization process of n-butyl methacrylate (BMA) monomer (Teo et al., 2009). Iron tri(acetylacetonate), 1,2-tetradecanediol, oleic acid, and oleyl amine were mixed in benzyl ether, under vigorous stirring. The mixture was heated gradually under nitrogen atmosphere and the blackcolored mixture was then cooled to room temperature by removing the heat source. The pre-formed particles were then encapsulated within the host poly(BMA) latex particles with 120 nm diameter and low size dispersion. The distribution of magnetite particles over the polymer particle population and within each polymer particle was nevertheless rather heterogeneous and the ratio of magnetite particles per polymer particle was determined as being equal to 50.
