Nonaqueous Emulsion Polymerisation

Description

The present invention relates to a nonaqueous emulsion comprising a solvent system and an emulsifier and to a process of reacting monomer educts to give a polymer in that nonaqueous emulsion. For stabilizing the emulsion, a copolymer is used as emulsifier. The nonaqueous emulsion is in particular suitable for carrying out water-sensitive, catalytic and oxidative polymerizations and polycondensations. The invention further relates to nanoparticles produced according to said process and their use.

The investigation of polymer nanoparticles is still a rapidly developing area in science. ¹¹¹ Nanoparticles prepared by emulsion polymerization, well established for coatings, paints and in flocculation processes, ¹²¹ are increasingly used in applications in the area of photonics, diagnostics and catalysis. ¹³¹ This can be attributed to their well-defined morphology and their unique physical and chemical properties such as size, optical properties and defined nature of the surface. ¹⁴¹

Of special interest are conjugated polymer nanoparticles, which are assumed to combine the processability and mechanical properties of latex particles with the electronic properties of conjugated polymers. ¹⁵¹ In particular, polyester nanoparticles are of particular interest as they combine biodegradability and biocompatibility with good mechanical properties and softening temperatures compared to low-density polyethylene and polystyrene.

Different strategies have been developed to form well-defined conjugated polymer nanoparticles, including direct synthesis of the nanoparticles in emulsion or dispersion polymerization or by creating dissolved conjugated polymer droplets via miniemulsion processes. ¹⁶¹ Since water is involved in all

these known emulsion processes, latex preparation of water-sensitive monomers (e.g. acid chlorides) or utilizing moisture sensitive reactions cannot be achieved by these traditional methods.

In particular polyester nanoparticles with the size and shape of traditional polymer latex particles, e.g. polystyrene, cannot be fabricated up to now. Three approaches towards polyester particles have been described:

The first one involves direct emulsion polycondensation of dicarboxylic acids and dioles in water catalyzed by surfactants, such as p- dodecylbenzenesulfonic acid or scandium tris(dodecyl sulfate).

Unfortunately, the excess water shifts the reaction-equilibrium against polyester formation. Therefore, only absolute molecular weights up to 1 500 g/mol have been reported for the polyester nanoparticles with mean diameters ranging from 100 to 500 nm. ^m

The second strategy involved particle formation by spraying polyester melts or polymers from supercritical solution. This technique leads to large particles (between 0.5 and 2 μm) and non perfect spherical shapes. ^[8]

The third approach is based on dispersion polymerization of polyester- oligomers at temperatures up to 200 ⁰ C. In this multi step process synthesis of the oligomers in bulk is followed by emulsification in silicon oil and then polycondensation of the oligomers at high temperatures. ¹⁹¹

To circumvent these severe drawbacks, a method for the preparation of nanoparticles and in particular of polyester nanoparticles under mild conditions is needed. One such method can be the nonequilibrium polyesterification between acid dichlorides and dioles. However, the use of acid dichlorides as monomers requires the absence of water during the emulsion polymerization to obtain high molecular weights.

Therefore, it was one object of the present invention to provide a nonaqueous emulsion suitable for carrying out water-sensitive polyreactions.

The object of the present invention is achieved by providing nonaqueous emulsion comprising a solvent system and a emulsifier, wherein a) the solvent system does not contain any compounds being able to interfere with water-sensitive compounds, b) the solvent system comprises two organic solvents, wherein one organic solvent forms a continuous phase and the other organic solvent forms a dispersed phase, and c) the emulsifier is a copolymer.

The solvent system used according to the invention does not contain any compounds having functional groups being able to interfere with water- sensitive compounds.

"To interfere" in terms of the present invention comprises all kinds of chemical interactions, reactions, influences or changes of structure or conformation which can occur between two compounds or functional groups. Any influence or variation of chemical properties, e.g. acidity, electrophilic or nucleophilc properties etc., is also included by this term.

A "water-sensitive compound" or "moisture-sensitive compound" in terms of the present invention is every compound which can be reacted with water. Moreover, the term "water-sensitive compound" comprises also a compound which can be reacted with a functional group having the chemical behaviour of water (e.g. nucleophilic properties, protic properties etc.). Preferably water-sensitive compounds in terms of the present invention are selected of acid halides, in particular acid chlorides, acid anhydrides, isocyanates or water-sensitive catalysts for polymerization or polycondensation reactions, preferably Luttinger, Grubbs, Schrock metallocene or Ziegler-Natta catalyst. M. E. Rogers and T. E. Long ¹¹¹¹ describe further water-sensitive compounds which are preferably polymerized in the process of the invention.

- A -

Functional groups having the chemical behaviour of water are known to the person skilled in the art. Preferably such functional groups have a protic character, i.e. are able to release a proton. Such functional groups are preferably selected from the group consisting of OH, NH ₂ , NHR', SH, SO ₃ H and/or COOH, wherein R ¹ is a branched or unbranched, substituted or unsubstituted C1-C10 hydrocarbon.

In a preferred embodiment the solvent system does not contain any compounds or solvents comprising protic groups. Such protic groups are preferably selected from the group consisting of OH, NH ₂ , NHR ¹ , SH, SO ₃ H and/or COOH, wherein R' is a branched or unbranched, substituted or unsubstituted C1-C10 hydrocarbon. The solvent system does for example not contain any mono- or polyvalent alcohols, phenols, amines, thioles, carboxylic acids, etc. Preferably the nonaqueous emulsion is free of water and/or alcohols, such as methanol, ethanol, glycerol, etc.

The solvent system comprises two organic solvents wherein one organic solvent forms a continuous phase and the other organic solvent forms a dispersed phase. In a preferred embodiment, the two organic solvents are immiscible. According to a preferred embodiment a nonpolar solvent forms the continuous phase and a polar aprotic solvent forms the dispersed phase. Thereby, any combination of at least two organic solvents can be used as long as they meet these criteria.

A polar solvent in terms of the present invention is any solvent the molecules of which have a permanent dipole moment. A nonpolar solvent consists of moleculs which have no permanent dipole moment. In the sense of the invention, polar solvents preferably have a dielectric constant ε ≥ 30, more preferably > 32 and most preferably > 35 (25 ⁰ C). In contrast, nonpolar solvents preferably have a dielectric constant ε < 30, more preferably < 28 and most preferably < 25 (25 ⁰ C). In another preferred embodiment of the invention δε between the polar solvent and the nonpolar solvent being part of the emulsion system according to the present invention is ≥ 5, more

preferably ≥ 10 and most preferably > 15 (25 ⁰ C).

The nonpolar solvent in terms of the present invention comprises also a mixtures of nonpolar solvents. Accordingly, the term polar solvent can comprise mixtures of polar solvents.

The nonpolar solvent is preferably selected from a branched or unbranched, linear or cyclic alkane, alkene, alkyne, benzene, perhalogenated hydrocarbons, e.g. tetrachloromethane or combinations thereof. Any nonpolar alkane, alkene or alkyne can be used as long as it is liquid at the temperature the corresponding nonaqueous emulsion is to be used. Optionally the nonpolar solvents can be substituted by any nonpolar substituents such as aliphatic or aromatic substituents.

According to a preferred embodiment of the invention the nonpolar solvent forming the continuous phase is selected from the group consisting of n- hexane, tetradecane or cyclohexane or mixtures thereof and the polar aprotic solvent forming the dispersed phase is selected from the group consisting of acetonitrile, DMF, DMSO, dimethylacetamide, N- methylpyrrolidone, N-methylformamide, gamma-butyrolactone, 4-methyl-1 ,3- dioxolan-2-on, sulfolane, nitrobenzene or nitromethane or mixtures thereof.

Acetonitrile is a particular suitable solvent for conjugated polymer synthesis. Particular preferred solvent systems comprise acetonitrile and cyclohexane or DMF and n-hexane.

The ratio of the polar aprotic solvent forming the dispersed phase to the nonpolar solvent forming the continuous phase in the nonaqueous emulsion is preferably about 1 :2 to about 1 :15, more preferably about 1 :5 to about 1 :12, and most preferably about 1 :10.

In a preferred embodiment the copolymer used as emulsifier in the nonaqueous emulsion system is a block copolymer, more preferably it is a

A-B block copolymer, a statistic copolymer or a graft copolymer. The copolymer acts as stabilizer of the dispersed phase.

All copolymers used in the present invention are preferably derived from monomers which are soluble in the continuous phase and from monomers which are soluble in the dispersed phase of the emulsion system

Monomers which are soluble in the continuous phase are preferably selected from monomers of hydrophobic polymers, in particular branched or unbranched poly C ₂ -Ci ₀ -alkylenes which can be substituted arbitrarily as long as the hydrophobic character of the polymer is maintained. In a particular preferred embodiment such monomers are selected from isoprene, butadien or styrene or combinations thereof.

Monomers which are soluble in the dispersed phase are preferably selected from monomers of polar polymers, in particular monomers of poly (methylmethacrylate), poly(acrylnitrile), poly(2-fluoroacrylate), poly (vinylidencarbonitrile), poly(acrylonitrile), poly(cyanoacrylate) or poly (acrylamide) or combinations thereof.

Accordingly, block copolymers according to the present invention preferably comprise at least one block A and at least one block B. Block A is preferably soluble in the continuous phase and a block B is soluble in the dispersed phase of the emulsion system.

In a further preferred embodiment block A generally need be characterized only in that it is hydrophobic and therefore is soluble in the continuous phase, i.e. the nonpolar solvent of the emulsion system. Thus, block A is preferably selected from hydrophobic polymers, e.g. branched or unbranched poly C ₂ -Ci ₀ -alkylenes which can be substituted arbitrarily as long as the hydrophobic character of the polymer is maintained. In a particular preferred embodiment, block A is selected from polyisoprene, polyethylene, polypropylene, poly(isobutylene), polybutadiene, polystyrene,

or combinations thereof.

In contrast, block B need be characterized only in that it is polar and therefore is preferably soluble in the dispersed phase, i.e. the polar aprotic solvent. Thus, block B is preferably selected from polar polymers, e.g. poly (methylmethacrylate) (PMMA), poly(acrylnitrile), poly(2-fluoroacrylate), poly (vinylidencarbonitrile), poly(acrylonitrile), poly(cyanoacrylate) or poly (acrylamide) and combinations thereof.

In a especially preferred embodiment of the invention polyisoprene-block- polymethylmethacrylate (PI-b-PMMA) is used as copolymer (i.e. block A is polyisoprene and block B is polymethylmethacrylate). Poly(isoprene) in comparison to poly(styrene) is known for its higher solubility in cyclohexane and PMMA as second block is known for its insolubility in cyclohexane but its excellent solubility in acetonitrile.

Generally.the molar ratio of block A to block B in the block copolymer is preferably from about 0,1 :1 to about 20:1 , more preferably from about 0.1 :1 to about 10:1 und in particular preferred from about 0.1 :1 to about 3:1. In a preferred embodiment concerning in particular a process for a polycondensation reaction according to the invention the molar ratio of block A to block B can be from about 3:1 to about 10:1 and in particular from about 3.1 :1 to about 5:1.

Statistic copolymers in the sense of the present invention comprise copolymers comprising statistically dispersed hydrophobic monomer units corresponding to the monomer units for block A, and hydrophilic monomer units corresponding to the monomer units for block B. In the statistic copolymers the molar ratio of hydrophilic monomer units to hydrophobic monomer units is preferably from 1 :0.1 to about 1 :50, more preferably 1 :0.1 to about 1 :30, even more preferably from 5:95 to 15:85, more preferably from 8:92 to 13:87 and especially preferably 10:90.

The molecular weight of all copolymers used is preferably about 2.000 to about 150.000 g/mol, more preferably about 2.500 to about 70.000 g/mol and most preferably about 3.000 to about 45.000 g/mol.

The nonaqueous emulsion comprises preferably from 0,1 to 10,0 percent copolymer based on the total weight of the emulsion, more preferably from 0,5 to 5,0 percent by weight, even more preferably 0,8 to 3,0 percent by weight and most preferably from 1 ,0 to 2,0 percent by weight.

The size of the dispersed droplets (mean droplet diameter), i.e. of the dispersed polar solvent, in the emulsion system ranges preferably from about 1 to about 1000 nm, more preferably from about 1 to about 500 nm, more preferably from about 1 to about 200 nm, more preferably from about 1 to about 100 nm, more preferably from about 5 to about 80 nm, more preferably from about 10 to about 70 nm, more preferably from about 10 to about 60 nm, more preferably from about 10 to about 50 nm, more preferably from about 10 to about 40 nm, more preferably from about 10 to about 30 nm and most preferably from about 15 to about 30 nm. The size of the droplets of the dispersed phase can be varied by the ratio of dispersed phase to continuous phase, time and intensity of stirring or ultrasonification, type or composition of emulsifier used. The size of the droplets of the dispersed phase can be determined via the solubility parameters δ\ of the solvents forming the respective emulsion system, as defined by Hansen. ¹¹⁰¹ In general, the miscibility of one component/solvent with the other decreases if the difference in δ\ increases. Thus, the droplet diameters can be varied by choosing a higher solubility difference of the solvents constituting the solvent system. For example DMF in n-hexane (δδ _t =10.0 J ^1/2 cm ^3/2 mol ^"1 ) can be compared to acetonitrile in cyclohexane (δδ _t =7.6 J ^1/2 cm ^3/2 mol ^'1 ). This property establishes a lower surface to volume ratio for the DMF droplets in n-hexane and therefore leads to bigger droplet diameters in the formed emulsions as compared to acetonitrile in cyclohexane (see Example 1).

For forming the emulsion system the components, i.e. the solvents constituting the solvent system and emulsifier, are simply mixed by any means known to the person skilled in the art, e.g. by stirring, shaking etc., at a temperature between the freezing point and the boiling of the solvents forming the solvent system, preferably at room temperature. Emulsification can be promoted by applying high shear rates/forces for e.g. 10-60 min, preferably about 20 min, e.g. by a sonic agitator, a jet disperser or a microfluidizer.

It is another object of the present invention to provide a process for reacting monomer educts in a nonaqueous emulsion according to the invention to give a polymer.

The strategy for such a nonaqueous process suitable for the preparation of nanoparticles by moisture sensitive polymerization reactions consists of two steps: (i.) Setting up an emulsion of two organic solvents by using an appropriate copolymer according to the invention and (ii.) polymerizing polymer nanoparticles inside the dispersed organic solvent, whereby the dispersed droplets are acting as "nanoreactors". Anhydrous organic solvents allow one to perform water-sensitive polymerizations inside the

"nanoreactors" and to produce nanoparticles without involving water in one of the phases.

Thus, in a preferred embodiment of the invention the reaction of the monomer educts takes place in the dispersed phase of the nonaqueous emulsion.

The reaction taking place in the dispersed phase is preferably a polyaddition, a polymerization or a polycondensation reaction.

Polyaddition reactions in the sense of the present invention are polyreactions proceeding stepwise, wherein polyaddition products are formed by multiple addition of di- or polyfunctional educts in independent

single reactions (step reactions) via the formation of reactive oligomers as discrete intermediates. These include both unipolyaddition reactions starting out from two identical monomer types and cyclopolyaddition reactions, wherein more than two different monomer types are used.

Polymerization reactions in the sense of the present invention are polyreactions, whereby monomers are linked by splitting up multiple bonds or ring opening via a chain reaction.

The polyaddition or polymerization reaction can be cationic, radical, anionic or metal-catalyzed.

The polyaddition reaction of the invention can be initiated, besides adding a catalyst, for example, by increasing the temperature. Radical polymerizations are preferably initiated by the use of peroxides. One embodiment of the invention concerns the use of metal catalysts for polymerizations and polycondenstions, e.g. Luttinger, Grubbs, Schrock, metallocene, Ziegler-Natta catalysts, anhydrous iron (III) chloride. In addition, the use of catalyst-mediated polycondensations, e.g. by Yamamoto catalysts, is a preferred embodiment of the invention.

Preferred examples of polyaddition reactions are the production of polyurethanes from multifunctional hydroxy compounds and multifunctional isocyanates, the production of polyureas from multifunctional amines and multifunctional isocyanates as well as the production of polypeptides from multifunctional epoxides and multifunctional amines, thiols or/and hydroxy compounds.

Polymerization reactions of thiophene, in particular 3,4- ethylenedioxythiophene (EDOT), or acetylene monomers are especially preferred reactions.

In a further preferred embodiment, the reaction taking place in the dispersed

phase is a polycondensation reaction. Polycondensation reactions in the sense of the present invention are polyreactions, whereby monomers link by splitting off reaction products, e.g. water, via stepwise condensation to give polycondensates, e.g. esterification. The polycondensation reaction of an acid halide, preferably an acid chloride, with a multifunctional, preferably difunctional compound is particularly preferred. As preferred functional groups, the multifunctional compound comprises at least two OH, NH ₂ or SH, with combinations of these groups within one compound also being comprised. The use of diols, diamines or dithiols is preferred.

In a preferred embodiment, a catalyst and/or an acid acceptor, respectively, is added to the system during the polycondensation reaction. Suitable catalysts are known to the skilled person. The use of tertiary amines, especially trimethylamine or pyridine is preferred.

The polycondensation reaction is especially suitable for producing polyesters. According to the prior art polyesters are mostly carried out by direct esterification or transesterification at high temperatures. The increased temperatures (above 200 ⁰ C) are necessary thereby to remove the released condensate from the reaction mixture and, thus, achieve high molar weigths of the resulting polymer. Due to the high temperatures required during the production of the polyester and the high water sensitivity of the employed monomers such as acid chlorides it is very difficult according the methods of the prior art to prepare polyesters in emulsion. The polycondensation according to the invention is preferably carried out at tempeatures between 5 °C and 80 ⁰ C, preferably room temperature.

By the polycondensation reaction according to the invention e.g. polyesters, polyamides, polyurethanes and polycarbonates can be produced.

In one embodiment of the invention, the monomer educts used in the reactions according to the invention are monomers of the same type. Accordingly homopolymers can be prepared. In another embodiment of the

invention, at least two different types of monomer educts are used. Accordingly heteropolymers or copolymers can be prepared.

In preferred embodiment of carrying out the process of the invention, the nonpolar solvent forming the continuous phase of the emulsion system such as cyclohexane is provided in a first step. Subsequently, for forming micelles, a copolymer such as PI-b-PMAA is added. After micelles have formed, the polar solvent forming the dispersed phase is added.

Nanoreactors filled with polar solvent are formed. The forming of the dispersed phase can be promoted as outlined above.

If any kind of catalyst to be used in the following polyreaction is to be added, it is preferred to add this catalyst together with the polar solvent so that it is mainly comprised by the nanoreactors.

A first type of monomer preferably having better solubility in the polar solvent constituting the dispersed phase than in the nonpolar solvent forming the continuous phase can be added simultaneously with the polar solvent or after the polar solvent, i.e. after the nanoreactors have been formed. If only one identical, i.e. one type of monomer is reacted in the polymerization, polyaddition or polycondensation reaction, the monomer is preferably added after formation of the nanoreactors.

If different types of monomers are to be reacted it is preferred to add a first type of monomer simultaneously with the polar solvent. After formation of the emulsion system with a first type of monomer dissolved in the dispersed phase, a second type of monomer is added if necessary.

The second monomer can be added all at once or dropwise. However, dropwise adding allows to control the stoichiometry more easily than in the case where the second monomer is added all at once. Thus, for example, by the slow dropwise addition method polyesters with three times higher molecular weight than polyesters prepared by complete monomer addition

can be obtained (Example 2).

After diffusion of the second monomer into the nanoreactors, the polymerization, polyaddition or polycondensation reaction takes place therein, preferably after the reaction is initiated as outlined above.

After completion of the polymerization reaction dispersed polymer nanoparticles are present. This polymer nanoparticles can be seperated, for example, by precipitation, filtration, centrifugation or combinations thereof.

The exemplary production of a polyester nanoparticle in a nonaqueous emulsion system according to the invention is shown in Fig. 1.

Another aspect of the invention relates to the the formation of core-shell structures. Up to now core-shell structures are typically formed in emulsion by the sequential addition of monomers which can be polymerized only by free radical polymerization. This emulsion system according to the invention offers the opportunity to incorporate polycondensates as rigid core making new spherical multi-layer structures accessible. Thus, in a preferred embodiment the invention is related to a process wherein following a first reaction with one or more first educts, with a polymer intermediate being formed, a second reaction is carried out with one or more second educts, said second educt(s) preferably being added to the polymer intermediate of the first reaction. Preferably said said second educt(s) are added covalently.

A further aspect of the invention relates to the production of preferably spherical nanoparticles comprising polymers of high molecular weight which are obtained by the process of the invention.

In a preferred embodiment, these polymers have molecular weights from 1.000 to 10.000.000 g/mol, more preferably 1.000 bis 1.000.000 g/mol, more preferably 1.000 to 500.000 g/mol, more preferably 1.000 bis 100.000 g/mol, even more preferably 1.000 to 50.000 g/mol and most preferably 2.000 bis

30.000 g/mol. In a particular preferred embodiment of the invention polyesters having molecular weights from 500 to 50.000 g/mol, more preferably 1.000 bis 40.000 g/mol, more preferably 1.500 to 30.000 g/mol, more preferably 2.000 bis 30.000 g/mol, even more preferably 5.000 to 25.000 g/mol, more preferably 7.000 bis 20.000 g/mol, and most preferably 8.000 bis 15.000 g/mol.

In a further preferred embodiment, the nanoparticles have mean diameters between 1 and 500 nm, more preferably between 10 and 100 nm, even more preferably between 10 and 80 nm, still more preferably between 10 and 60 nm, more preferably between 12 and 50 nm, more preferably between 14 and 45 nm, more preferably between 16 and 40 nm, more preferably between 18 and 35 nm and most preferably between 20 and 30 nm.

In another preferred embodiment the nanoparticles of the invention can form aggregates of nanoparticles. The mean diameter of such nanoparticle aggregates ranges between 100 nm to 10 μm, more preferably 500 nm to 5 μm and even more preferably from 500 nm to 2 μm.

A still further aspect of the present invention relates to nanoparticles which can be obtained according to the process of the invention. These nanoparticles are preferably spherical and are of a high uniformity regarding size and shape.

Another aspect of the invention concerns the use of nanoparticles obtained according to the process of the invention. The small nanoparticles according to the invention are required to obtain high fluidity as well as smooth and thin coatings. Moreover, in particular, polyester nanoparticles combine biodegradability and biocompatibility with good mechanical properties and softening temperatures, compared to low density polyethylene and polystyrene. The nanoparticles of the invention, therefore, are used in various areas including pharmaceutics, cosmetics, catalysis and as powder

coatings. In particular, they are used as biocompatible binding agents in pharmaceutical or cosmetic industry, in particular, for creams and ointments or as carriers of active agents for powder coating surfaces, in particular, for dyeing or rendering a surface hydrophilic or hydrophobic, for producing dispersion paints or toner particles, in particular, in printing industry or in catalysis. Moreover, they can be employed as marker particles in visual immunodiagnostic assays, for example, for hormones, antigens or antibodies

Fig. 1 Preparation of polyester nanoparticles in a nonaqueous emulsion system

Fig. 2 Particle size distribution of polyester nanoparticles (Exp.2), mean particle size 38 nm (std. dev. ± 7 nm) determined by SEM (based on 100 particles)

Fig 3 SEM images of the PEDOT nanoparticles; a) b) sample Il c) sample III

Examples

General Remarks

Adipoyl dichloride (ADCI), malonyl dichloride (MDCI) 1 ,4-bis(hydroxymethyl) cyclohexane (BHC), terephthaloyl dichloride (TDCI), and anhydrous ethylene glycol (EG) were purchased from Sigma-Aldrich and used as received. Cyclohexane, hexane, acetonitrile, N,N ^' -dimethylformamide (DMF), extra pure triethylamine (TEA), and pyridine were obtained from ACROS Organics, and dried over molecular sieves (4 A). Acetylene gas dissolved in acetone was supplied in a high pressure cylinder by Linde (Wiesbaden, Germany). 3,4-Ethylenedioxythiophene was obtained from H.C.-Starck (Leverkusen, Germany). Poly(isoprene)-block-poly(methylmethacrylate) copolymer and Polyisoprene-block-polymethylmethacrylate (PI-b-PMMA) copolymer were prepared using a sequential anionic polymerization technique.

GeI permeation chromatography (GPC) vs. poly(styrene) and poiy(isoprene) (Pl) standard, respectively, was carried out at 30 ⁰ C using MZ-GeI SDplus 10E6, 10E4, and 500 columns, an ERC RI-101 differential refractometer detector, and THF as eluent. Prior to chromatography, samples were filtered through a 0.2 μm Teflon filter (Millipore) in order to remove insoluble impurities. Composition of the PI-b-PMMA copolymer was determined in CDCI ₃ as solvent by ¹ H-NMR spectroscopy using a Bruker Avance Spectrometer operating at 500 MHz. FT-IR spectra were obtained by a Nicolet 730 FT-IR spectrometer using a Thermo Electron Endurance ATR single-reflection ATR crystal. SEM images were taken by a Zeiss Gemini 912 microscope. For SEM sample preparation, the dispersed nanoparticles were drop casted on silica wafers. Emulsions were characterized by means of dynamic light scattering (DLS) at low concentrations using a Malvern Zetasizer 3000. All other DLS measurements were performed at low concentrations on a ALV 5000-correlator using a He/Ne-Laser operating at 632.8 nm.

Example 1 : Preparation of different nonaqueous emulsion systems

Two different non-aqueous emulsion systems were prepared. The first consisted of acetonitrile as the dispersed and cyclohexane as the continuous phase. The second system was composed of DMF in n-hexane as the dispersed phase. For stabilization of the emulsions, a PI-b-PMMA copolymer having a number average molecular weight of 30,500 g/mol (dispersity 1.1 ) and a block composition of 70 % Pl and 30 % PMMA was used. In both systems the Pl-block, which is only soluble in the nonpolar continuous phase, acts as the stabilizing and the PMMA-block as anchor moiety for the dispersed polar organic droplets.

To study the size of the dispersed droplets, different non-aqueous emulsions were prepared by varying the amount of stabilizer and then characterized by means of dynamic light scattering at scattering angles of 60 and 90° (Table

1 ). In the investigated range the diameter of the acetonitrile droplets in cyclohexane was always smaller compared to those from DMF droplets in n- hexane which is in accordance to the solubility parameters δ _t for the used solvents.

Table 1 : Characteristics of different non-aqueous emulsions

Example 2: Synthesis of polyester nanoparticles

PI-b-PMMA copolymer (0.450 g) was stirred magnetically in cyclohexane (24.0 g, 285 mmol) at room temperature. 1 ,4-Bis(hydroxymethyl) cyclohexane (BHC, 0.87 g, 6.0 mmol) was dissolved in acetonitrile (3.0 g, 73 mmol) and added dropwise to the cyclohexane/copolymer solution. The emulsion was formed by stirring the mixture for 2 h, adding dry pyridine (1.21 g, 12.0 mmol), and sonication of the solution for 10 min. Subsequently, adipoyl dichloride (ADCL, 1.21 g, 6.60 mmol) was added dropwise (approx. 4.8 ml/h) to the emulsion. Polyesterifications reaction proceeded while stirring for 2 h. The reaction product was placed in a separating funnel and an excess of acetonitrile was added to remove residual emulsifier and generated hydrochloride. The precipitated particles were separated, washed twice with acetonitrile to give 1 g of a white solid that was dried in vacuum over night or directly redispersed in n-hexane.

In other reactions ADCL was replaced by malonyl dichloride (MDCI) and terephthaloyl dichloride (TDCI), respectively, and BHC was optionally replaced by ethylene glycol (EG).

To obtain polyester nanoparticles the diole was dissolved in the polar organic solvent (acetonitrile or DMF) and emulsified in the nonpolar organic phase. Polymerization was started upon addition of the dichloride component. As the diole is only soluble in the polar phase, the polycondensation reaction only occurs in the dispersed phase since only there both monomers are present (Figure 1 ). During the polymerization TEA precipitated as a quaternary ammonium salt while the pyridine-hydrochloride remained soluble in the continuous phase. Hence, the hydrochloride which was released during the polycondensation reaction could no longer participate in the reverse reaction. After polymerization, the nanoparticles were isolated by precipitation upon addition of excess polar phase.

Non-aqueous emulsion polycondensations led to polyester particles having mean diameters smaller than 60 nm. The weight average molecular weight of the polymers, determined by GPC versus polystyrene standards, was as high as 22 000 g/mol. The use of acetonitrile instead of DMF as the dispersed phase led to higher molecular weights. This can be explained by the fact that acetonitrile is a better solvent for the polyesters and polymerization could proceed longer in solution before the polyester precipitated within the dispersed droplets. Additionally, DMF can undergo hydrolytic degradation forming formic acid which might terminate the polycondensation reaction.

To obtain high molecular weight polyesters the dichloride component was added dropwise in a 10% excess to the emulsion using a syringe pump (Table 2, Exp. A1-A3, A7-B9). Continuous addition of the acid dichloride ensured a complete consumption of the acid dichloride before new monomer was added.

Table 2: Polyesterification reactions performed in non-aqueous emulsions - experimental conditions and results, the dispersed phases were CH ₃ CN in A and DMF in B experiments, the continuous phases were cyclohexane in A and n-hexane in B experiments.

^a> determined by dynamic light scattering, particles redispersed in hexane at low concentration ^b> determined by GPC in THF versus polystyrene standards ^c) dispersity of the polymer, determined by GPC ^d) polymers insoluble in THF ^e) no polymerization

⁰ acid dichloride component was added slowly in 10% excess using a syringe pump

Successful polymerizations were confirmed by matrix assisted laser desorption ionization - time of flight (MALDI-TOF) mass spectrometry (MS) which showed in all cases the repeating units of the polyesters. For polymer analysis, the molecular weight distributions were calculated on the basis of the recorded mass spectra (Table 3).

Table 3: Molecular masses of the polyesters determined by MALDI-TOF mass spectrometry for the high molecular weight polyesters

For the investigated polyesters absolute weight averaged molecular masses up to 9 200 g/mol (Mn 7 600 g/mol, dispersity 1.2) were calculated.

Due to their residual emulsifier shell the particles could be redispersed in n- hexane after purification. The obtained dispersions showed a long-term stability (> 4 weeks) and were characterized by DLS to determine the mean particle diameters (Table 2).

To exclude influences of the PI-b-PMMA copolymer on the particle size measurements the particle size was additionally verified by scanning electron microscopy (SEM). A dispersion of particles in acetonitrile was drop casted onto a silicon wafer and the mean particle size was directly calculated from the scanning electron microscopy (SEM) images based on

100 particles. A typical SEM image and the particle size distribution are shown in Figure 2. The particles showed a perfect spherical shape and narrow particle size distribution. The SEM-based number average diameter was found to be 38 nm (± 7 nm) whereas the DLS-based number average diameter was found to be 43 nm (± 10 nm). This shows that the particles are dispersed separately in the n-hexane solution and that influences exerted by the stabilizer can be neglected.

Example 3: Synthesis of poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles PI-b-PMMA copolymer (0.530 g) was magnetically stirred in cyclohexane (24 g, 285 mmol) at room temperature. Anhydrous iron(lll) chloride (1.3 g, 8 mmol) was dissolved in acetonitrile (3 g, 73 mmol) and added dropwise to the cyclohexane/copolymer solution. The emulsion was formed by stirring the solution under Argon for 2 h.

3,4-Ethylenedioxythiophene monomer (0.500 g, 3.5 mmol) was added dropwise and polymerization proceeded while stirring under argon for 8 h. The reaction product was transferred to a separating funnel and a

methanol/acetonitrile (80/20 vol.-%) mixture was added in excess to remove the emulsifier and the residual iron salts. The precipitated particles were removed by centrifugation, washed with THF and acetonitrile to give a dark blue solid which was redispersed in cyclohexane.

The obtained nanoparticles could be precipitated upon addition of excess methanol/acetonitrile. FT-IR spectroscopy of the particles showed the characteristic ring vibration of the thiophene ring at 1470 cm ^"1 and of PEDOT at 1355 cm ¹ , which can be attributed to the quinoidal C-C and C=C 0 structure. Further vibrations at 1186, 1139, and 1080 cm ^"1 were assigned to the C-O-C bond stretching, whereby the C-S bond vibrations in the thiophene ring was found at 990, 840, and 695 cm ^"1 . As both blocks of the PI-b-PMMA copolymer are completely soluble in THF, it was possible to obtain pure PEDOT nanoparticles upon washing the precipitate with THF. 5 FT-IR spectra of the pure nanoparticles displayed no carbonyl bands, which would have indicated the presence of residual PI-b-PMMA copolymer. Thus, the emulsifier had been quantitatively removed from the nanoparticle surface.

0 The reaction was repeated with different amounts of emulsifier based on weight-% of cyclohexane and EDOT (Table 4).

Table 4: Characteristics of EDOT polymerizations in nonaqueous acetonitrile/cyclohexane emulsion, polymerizations performed in 24 g cyclohexane, 3g acetonitrile

5 ^c) weight-% of cyclohexane; ^d) by SEM

The obtained nanoparticles have a spherical morphology. For all prepared samples the number average diameters were found to be smaller than 30

nm (Figure 3, Table 4). This was calculated directly from the scanning electron microscopy (SEM) images based on 100 particles.

Example 4: Synthesis of poly(thiophene-3yl-acetic acid) nanoparticles

Polymerization was performed according Example 3; however thiophene-3- yl-acetic acid monomer (TAA, 0.500 g, 3.5 mmol) was dissolved in acetonitrile (1 g, 24 mmol) before performing the polymerization reaction.

The presence of the carboxylic acid group was demonstrated by FT-IR spectroscopy, which showed the characteristic -COOH vibration at 1729 cm ^{" 1} . The shape of the obtained particles was characterized by SEM, showing a spherical geometry and an average diameter of 28 nm (± 5 nm).

Example 5: Synthesis of poly(acetylene) nanoparticles

PI-b-PMMA copolymer (0.400 g) was magnetically stirred in cyclohexane (24 g, 285 mmol) at room temperature. Sodiumborohydride (0.03 g, 8 mmol), dissolved in a mixture of acetonitrile (5 g, 120 mmol) and ethanol (0.5 g, 4 mmol), was added dropwise to the cyclohexane/copolymer solution. The emulsion was formed by stirring the solution under argon for 2 h. Acetylene gas was passed from the supply cylinder to the reaction flask and then bubbled through the formed emulsion for 15 min. Cobalt(ll) nitrate hexahydrate (0.2 g, 0.7 mmol) was dissolved in acetonitrile (1 g, 24 mmol) and added dropwise to the stirred emulsion. Polymerization proceeded while bubbling acetylene through the reaction flask and stirring the emulsion for 25 min. The reaction product was placed in a separating funnel and excess acetonitrile was added to remove the emulsifier and the residual iron salts. The precipitated particles were removed, washed with THF and acetonitrile to give a black solid which was redispersed in cyclohexane.

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