Synthesis in Emulsions

The main disadvantage of the wet chemical methods widely used in the synthesis of nanosized particles is the formation of large aggregates. This becomes critical especially in the case when individual particles are a few nanometers in size. The alternative processes are those based on the ideology of the micro- or nanosize reactors and complex organized surfactants structures (surface active agents) or block copolymers as templates. 

Surfactant molecule can spontaneously form spherical aggregates called micelles or microemulsions. Differences between the micelles and microemulsions are in their scale, although recently these terms have been used interchangeably. Namely, the micelles have aggregates of 1-10 nm diameter, whereas the corresponding range for microemulsions lies from 10 to 100 nm [180]. 

Material Characteristics of nanoparticle Brief description of the process Refs. 

NiFe204 Crystallite size 5 nm Particle size 30 nm Water solutions of nickel nitrate or iron nitrate have been mixed with water solution of PAA followed by nitric acid addition. The green color transparent solution have been evaporated at 50 °C until transparent sol, which has been heated at 50 °C for 10 h to brown gel, followed by firing until nickel ferrite nanoparticles formation [130] 

BaTiOs Mono-disperse nanoparticles of 4-12 nm size Ethyl-hexane-iso-propoxide of titanium and barium has been injected to the biphenyl ether at 140 °C under argon or nitrogen. The mixture has been cooled down to 100 °C, mixed with H2O2 and stirred for 48 h followed by hydrolysis and crystallization under reverse micelle conditions [142] 

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Figure 9.17 Green fluorescent protein (GFP) synthesis in water-in-oil emulsion as visualized by fluorescence microscopy. (Adapted from Pietrini and Luisi, 2004). Shown are the compartments in which GFP has been expressed (green in the original), (a) Typical micrographs of the cell-free GFP synthesis in Span 80 (0.45% v/v)/Tween 80 (0.05% v/v)/aqueous solution (0.5% v/v) in mineral oil emulsion droplets, preparation at 4 °C incubation at 37°C (i) 0 min, (ii) 11 min, (iii) 23 min, (iv) 32 min, (v) 44 min, (vi) 57 min, (vii) 21 h. Negative control (viii) 0 min, (ix) 21 h. The bar represents 50 p.m. (b) Kinetics of the cell-free GFP synthesis in emulsion droplets, on average 10 droplets with diameters of 30-60 um are evaluated per time point, cell-free enhanced GFP synthesis in emulsion droplets (i, ii and iii are three independent experiments) and negative controi (iv and v are two independent experiments).

Attempts to fabricate nanoparticles directly from emulsions were unsuccessful, even when submicron emulsion droplet size has been used. The spontaneous aggregation of primary particles and droplets leads to the final particle size of 0.1 mm. To avoid aggregation, the new method of synthesis in emulsions has been suggested for the preparation of oxide particles of 5 10 nm size [186]. Thermally stable water-oil emulsions prepared with the addition of surfactant to obtain a narrow distribution of submicron droplets of uniform size and volume are shown in Fig. 5.8. 

The class I FruA isolated from rabbit muscle aldolase (RAMA) is the aldolase employed for preparative synthesis in the widest sense, owing to its commercial availability and useful specific activity of 20 U mg . Its operative stability in solution is limiting, but the more robust homologous enzyme from Staphylococcus carnosus has been cloned for overexpression [87], which offers unusual stability for synthetic purposes. Recently, it was shown that less polar substrates may be converted as highly concentrated water-in-oil emulsions [88]. 

As another case study a process synthesis of an emulsion polymerization process is given (Hurme and Heikkila, 1998). In emulsion polymerization unsaturated monomers or their solutions are dispersed in a continuous phase with the aid of an emulsifier and polymerized. The product is a dispersion of polymers and called a latex. The raw materials are highly flammable unsaturated hydrocarbons and the reaction is exothermic which both cause a risk. The main phases and systems in an emulsion polymerization plant are listed in Table 31. 

Finally, control of fluorapatite particle size (from 15 nm to 200 pm) and morphology can be achieved by varying precipitation conditions using aqueous precipitation from a micro-emulsion or by biomimetic synthesis in a gelatin matrix [129],... 

The determination of the enzyme activity as a function of the composition of the reaction medium is very important in order to find the optimal reaction conditions of an enzyme catalysed synthesis. In case of lipases, the hydrolysis of p-nitrophenyl esters in w/o-microemulsions is often used as a model reaction [19, 20]. The auto-hydrolysis of these esters in w/o-microemulsions is negligible. Because of the microstructure of the reaction media itself and the changing solvent properties of the water within the reverse micelles, the absorbance maximum of the p-nitrophenol varies in the microemulsion from that in bulk water, a fact that has to be considered [82]. Because of this, the water- and surfactant concentrations of the applied micro emulsions have to be well adjusted. 

The same principle can be applied using diisopropyl benzene dihydroperoxide (5, 181, 182). The synthesis of polymeric hydroperoxides in which the hydroperoxide groups occupy terminal positions in the polymer chain, was carried out in emulsion, using the system w-diisopropyl-benzene dihydroperoxide/ferrous ion/pyrophosphate the residual hydroperoxide groups on the polymer are protected from further reaction by the emulsion technique, the residence time in the aqueous phase being sufficiently short. 

As an extension of the HA film approach, Yun and coworkers [32] synthesized hyaluronan microspheres using the chemistry described above, but the synthesis was completed in emulsion in one step, yielding 5- to 20-pm microspheres. These microspheres were found to be biodegradable and released three times more pDNA when incubated with hyaluronidase in PBS (phosphate buffered saline) solution (vs enzyme-free PBS). As in the case of films, DNA release from the microspheres was dependent on the DNA loading. DNA-HA microspheres were not directly used for transfection instead, DNA obtained from release experiments was used in transfection of Chinese hamster ovary (CHO) cells using Lipofectamine. The relative levels of transfection over time had the same trend as DNA release from the DNA-HA microspheres and confirmed that released DNA is bioactive. 

Recent studies in the pharmaceutical field using MBR technology are related to optical resolution of racemic mixtures or esters synthesis. The kinetic resolution of (R,S)-naproxen methyl esters to produce (S)-naproxen in emulsion enzyme membrane reactors (E-EMRs) where emulsion is produced by crossflow membrane emulsification [38, 39], and of racemic ibuprofen ester [40] were developed. The esters synthesis, like for example butyl laurate, by a covalent attachment of Candida antarctica lipase B (CALB) onto a ceramic support previously coated by polymers was recently described [41]. An enzymatic membrane reactor based on the immobilization of lipase on a ceramic support was used to perform interesterification between castor oil triglycerides and methyl oleate, reducing the viscosity of the substrate by injecting supercritical CO2 [42],... 

Abele, S., Graillat, C., Zigmanis, A. and Guyot, A. (1999) Hemiesters and hemiamides of maleic and succimic acid synthesis and application of surfactants in emulsion plymerization with styrene and butyl acrylate. Polym. Adv. Technol, 10, 301-10. 

Zicmanis, A., Hamaide, T., Graillat, C., Monnet, C., Abele, S. and Guyot, A. (1997) Synthesis of new alkyl maleates ammonium derivatives and their use in emulsion polymerisation. Colloid Polym. Sci., 275, 1-8. 

Soula, O. and Guyot, A. (1999) Styrenic surfmer in emulsion copolymerization of acrylic monomers. I. Synthesis and characterization of polymerizable surfactants. Langmuir, 15,7956-62. 

The process of miniemulsion allows in principle the use of all kinds of monomers for the formation of particles, which are not miscible with the continuous phase. In case of prevailing droplet nucleation or start of the polymer reaction in the droplet phase, each miniemulsion droplet can indeed be treated as a small nanoreactor. This enables a whole variety of polymerization reactions that lead to nanoparticles (much broader than in emulsion polymerization) as well as to the synthesis of nanoparticle hybrids, which were not accessible before. 

In this special volume on polymer particles, recent trends and developments in the synthesis of nano- to micron-sized polymer particles by radical polymerization of vinyl monomers in environmentally friendly heterogeneous aqueous and supercritical carbon dioxide fluid media are reviewed by prominent worldwide researchers. Polymer particles are prepared extensively as synthetic emulsions and latexes, which are applied as binders in the industrial fields of paint, paper and inks, and films such as adhesives and coating materials. Considerable attention has recently been directed towards aqueous dispersed systems due to the increased awareness of environmental issues. Moreover, such polymer particles have already been applied to more advanced fields such as bio-, information, and electronic technologies. In addition to the obvious commercial importance of these techniques, it is of fundamental scientific interest to completely elucidate the mechanistic details of macromolecule synthesis in the microreactors that the polymer particles in these heterogeneous systems constitute. 

The major emulsion processes include the copolymerization of styrene and butadiene to form SBR rubber, polymerization of chloroprene (Fig. t -4) to produce neoprene rubbers, and the synthesis of latex paints and adhesives based mainly on vinyl acetate and acrylic copolymers. The product is either used directly in emulsion form as a paint or else the surfactants used in the polymerization are left in the final, coagulated rubber product. 

Jacobsen GB, Lee CT Jr, daRocha SRP, Johnston KP. Organic synthesis in water/carbon dioxide emulsions. J Org Chem 1999 64 1207-1210. 

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