Synthesis of Polymer Microspheres via Self-Assembly of

Ind. Eng. Chem. Res. 2007, 46, 3219-3225

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Synthesis of Polymer Microspheres via Self-Assembly of Monodisperse Precursor Particles Fiona Macintyre, Pol Besenius, and David C. Sherrington* Department of Pure and Applied Chemistry, Westchem Graduate School of Chemistry, UniVersity of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, UK

Spherical monodisperse vinyl copolymer particles have been prepared using three different techniques: surfactant-free emulsion polymerization (SFEP), precipitation polymerization (PP), and dispersion polymerization (DP). SFEP yielded methacrylic acid (MAA)-styrene (St) (MAA/St ) 25/75) copolymer particles with a diameter of ∼200 nm. PP yielded MAA-divinylbenzene (DVB) copolymer particles with a diameter of ∼5 µm (MAA/DVB ) 25/75) and of ∼1 µm (MAA/DVB ) 60/40), and also glycidyl methacrylate (GMA)DVB (GMA/DVB ) 60/40) copolymer particles with a diameter of ∼4.5 µm. DP was used to prepare GMASt (60/40) copolymer particles of diameter ∼1.5 µm. Attempts to self-assemble samples of each primary particle into spherical aggregates were made using high solids (33%) aqueous dispersions each in inverse suspension in toluene. Self-assembly was induced by Dean-Stark removal of the water in some of the toluene. No success was achieved with the two largest sized particles. However, both the ∼200 nm and the two 1-1.5 µm primary particles were successfully self-assembled into spherical aggregates provided the particles were functionalized with hydroxyl or carboxylic acid groups. The aggregates were further chemically modified in an attempt to improve the stability of each, and then all of the self-assembled materials were tested for stability in contact with a broad range of solvents. The “as-formed” aggregates are stable in nonpolar solvents and water but have poorer stability in solvents of intermediate polarity. However, the chemically treated analogues are stable in the broad range of solvents tested. Introduction Ion-exchange and related resins are an extremely important class of porous polymers, which now find widespread use in applications as broad as medicine, combinatorial synthetic chemistry, catalysis, metals extraction, and numerous separation and purification processes.1 These resins are generally based on cross-linked polystyrene or polymethacrylates and are produced in a spherical form by suspension polymerization.2-4 Two main morphological variants are available. The first group is termed gel-types. These are lightly cross-linked (usually 10%), have a permanent porous structure, and will sorb significant levels of both thermodynamically compatible or noncompatible solvents. This second group is available with a variety of tailored pore structures such that some have a large population of micropores (IUPAC < 2 nm) and hence high surface area, while at the other extreme some have mainly macropores (IUPAC > 50 nm) and relatively low surface area. On balance, the porous resins are perhaps more versatile in terms of their applications. Interestingly, the method of synthesis of these is a one-pot suspension polymerization methodology. The process evolved via experimentation in various ion-exchange resin companies and is extremely complex.5 This involves concurrent free radical polymerization of appropriate comonomers, cross-linking of growing polymer chains, polymer phase separation to form primary particles, and finally fusion and infilling of these particles to form the final stable and rigid pore structure. Remarkable as it may seem, this process is now * To whom correspondence should be addressed. Tel.: 0044 141 548 2799. Fax: 0044 548 4246. E-mail: [email protected].

extremely well-developed and controlled, so that a variety of porous materials can be synthesized on both a laboratory and an industrial scale with high reproducibility. Notwithstanding the considerable success of these materials as a group, they still have some important limitations, and in particular each grade is usually characterized by having a finite distribution of the pore sizes and this can be very large. For some applications, this is useful, but there are others (e.g., as catalyst supports, as chromatographic stationary phases) where a much tighter distribution may well be an advantage. With this background, we wondered recently whether it might be possible to synthesize porous polymers in a more rational way by starting with some small, compositionally well-defined, uniformly sized spherical primary polymer particles, then getting these to self-assemble into a close-packed array to form larger spherical particles, each with a very narrow distribution of pore sizes corresponding to the gaps between the primary particles. When used in column operations, such particles might provide improved ease of packing and low back-pressures because of the overall size of individual aggregate particles, coupled with good kinetic performance because of the fractal structure of each involving the small primary particles. A similar approach is being adopted in other laboratories employing inorganic primary particles rather than organic polymeric ones,6,7 and indeed binary mixtures of organic and inorganic particles.8 Recently, we have shown9 that monodisperse polymer particles ∼200 nm in diameter synthesized by surfactant-free emulsion polymerization10 (see Figure 1 in ref 10) can be encouraged to self-assemble into larger microparticles (see Figure 4 in ref 9) by dispersing a concentrated aqueous emulsion (33% solids) of these primary particles in toluene followed by azeotropic removal of the water with some of the toluene (Scheme 1). The particles produced have a rather low surface area, which corresponds to the sum of the external surface areas of the constituent primary particles. However, very recently we have for the first time succeeded in

10.1021/ie0608354 CCC: $37.00 © 2007 American Chemical Society Published on Web 12/01/2006

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Scheme 1. Self-Assembly of Monodisperse Primary Particles To Form Close-Packed Spherical Aggregates via Dean-Stark Removal of Water from Droplets of an Aqueous Dispersion (33% Solids) of the Primary Particles Suspended in Toluene

synthesizing the small primary particles with their own porous structure,11 and we are now planning to get these to selfassemble and in doing so generate larger particles with predetermined bimodal pore structure. Meanwhile, we have been trying to broaden the base of the self-assembly process to evaluate the size range of primary particles to which this process might be successfully applied and now report on the selfassembly of monodisperse polymer particles themselves prepared using dispersion12-14 and precipitation15 polymerization techniques. Experimental Section Materials. Divinylbenzene (DVB) (80% grade), styrene (St), methacrylic acid (MAA), sorbitan monooleate (Span 80), azobis-isobutyronitrile (AIBN), polyvinylpyrrolidone (Μn ≈ 40 000 g mol-1), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (ETC), 1,7-diaminoheptane, and diisocyanatohexane were from the Aldrich Chemical Co. Glycidyl methacrylate (GMA) was supplied by Dow Chemicals, and ammonium persulfate (APS) was from Fisons. MAA was purified by distillation and AIBN by recrystallization from acetone at room temperature. The inhibitor in the St and DVB, p-tert-butylcatechol, was removed by passing each monomer through a column of silica. All other materials, including bench solvents, were used as supplied. Surfactant-Free Emulsion Polymerization.10,16 Primary particles SFEP were prepared essentially as previously reported10 using a parallel-sided glass reactor. The aqueous phase was 140 cm3 distilled water and was charged into the reactor. The comonomers were 37.1 mL of St and 12.4 mL of MAA (St:MMA 75:25) targeted to yield a polymer solids content of 33% in the final emulsion. These were added when the aqueous phase had reached reaction temperature, and the mixture was then stirred at 430 rpm for 15 min. After this, 0.05 g of APS (1.4 × 10-3 mol L-1) dissolved in 10 cm3 distilled water was introduced to the reactor, and the stirrer speed was reduced to 350 rpm. Polymerization was allowed to continue for 24 h at 70 °C to yield the required 33% solids emulsion. The latter was allowed to cool and was subsequently used as prepared. Precipitation Polymerzization.15 As an example, a mixture of 15 mL of MAA and 10 mL of DVB (MAA:DVB, 60:40 v/v) to provide 5 wt % of comonomers in the total of solvent, along with AIBN (2 mol % wrt polymerizable double bonds), were added to a glass bottle containing a mixture of 300 mL of

acetonitrile and 200 mL of toluene. After being purged with N2, the bottle was gently rolled in an incubator as the temperature was ramped from room temperature to 60 °C. The polymerization was left for 24 h, and the ∼1 µm diameter monodisperse particles (PP3) that had formed were collected by filtration. These were then washed with acetone and vacuumdried at 40 °C. Dispersion Polymerization.12-14 A mixture of 7.5 g of GMA and 5 g of St (GMA:St 60:40 v/v) to provide 10 wt % of comonomers in the total of solvent and 0.125 g of AIBN (1 wt % wrt total amount of comonomers) were weighed into a 180 mL glass bottle. Next, 100 mL of ethanol, 10 mL of water, and 5 g of PVP (4 wt % based on total weight) were added. After being purged with N2, the bottle was gently rolled in an incubator while the temperature was ramped from room temperature to 60 °C. The polymerization was left for 24 h, and the ∼1.5 µm diameter monodisperse particles (DP) that had formed were collected by filtration, washed with ethanol, and then vacuum-dried at 40 °C. Acid Hydrolysis of Epoxide Groups. As an example, 10 g of primary particles DP was weighed into a 100 mL roundbottomed flask containing a small magnetic stirrer, and 43.7 mL of 5 M H2SO4 (10/1 mole ratio of H+/epoxy) was added. The reaction mixture was then refluxed for 5 h. After being cooled to room temperature, the reaction mixture was neutralized using aqueous NaOH solution. Finally, the hydrolyzed particles (H-DP) were recovered by filtration using a membrane filter and were washed several times with ethanol before being dried overnight in a 40 °C vacuum oven. Inverse Suspension Aggregation Procedure.9 1.485 g of primary particles (PP1-3 or DP) was dispersed in 4.5 mL of distilled water to give a 33% solids content suspension. As the emulsion product SFEP already existed as a 33% solids content latex, 4.5 mL of this was taken and used directly. Next, 2 g of sorbitan monooleate was dissolved in 45 mL of toluene, and this solution was added to a silanized three-necked 250 mL flask. Stirring at a rate of 250 rpm (350 rpm for emulsion particles) was then initiated, and the mixture was purged with N2. The aqueous polymer dispersion was then added. Once the formation of a stable suspension had been achieved, the temperature was increased to 108 °C to initiate Dean-Stark distillation. Finally, when water ceased to be removed from the reaction, heating was stopped and the flask was left to cool. The toluene supernatant was then decanted off and replaced with clean toluene. This process was repeated twice with heptane before the aggregates, if formed, were dried in a vacuum desiccator at room temperature. Chemical Stabilization Procedures. Procedure A. To 0.1 g of self-assembled aggregates A-SFEP or A-PP3 was added 0.06 g (100 mol % with respect to acid groups on aggregates) of an aqueous solution of ETC. The mixture was gently rolled in a small glass vial for 10 min before 0.02 g (50 mol % with respect to acid groups of aggregates) of aqueous 1,7-diaminoheptane was added. The reaction mixture was rolled for 24 h at room temperature. Finally, the chemically stabilized aggregates CS-A-SFEP and CS-A-PP3 were collected by filtration and washed in heptane before being left dry at room temperature in a vacuum desiccator. Procedure B. In this instance, the chemical stabilization procedure was employed concurrently with the primary particle self-assembly procedure as follows. 4.5 g of diisocyanatohexane was dissolved in 45 mL of toluene containing 2 g of Span 80. This solution was added to 1.485 g of primary particles H-DP in 4.5 mL of water. These two phases were then used in the

Ind. Eng. Chem. Res., Vol. 46, No. 10, 2007 3221 Table 1. Synthesis of Monodisperse Primary Particles via Surfactant-Free Emulsion (SE), Precipitation (PP), and Dispersion (DP) Polymerization Methodologiesa primary particle

comonomer mole ratio

solids (%)

SE

MAA/St 25/75 MAA/DVB 25/75 GMA/DVB 60/40 MAA/DVB 60/40 GMA/St 60/40

33

PP1 PP2 PP3 DP

solvent water

gravimetric yield (%)

particle size (µm)

∼100

0.2

5

acet

75

5.0

2

acet

67

4.5

5

acet/tol 6/4 H2O/EtOH 1/10

82

1.0

72

1.5

10

a MAA ) methacrylic acid; St ) styrene; GMA ) glycidyl methacrylate; DVB ) divinylbenzene; acet ) acetonitrile; tol ) toluene; EtOH ) ethanol.

inverse suspension self-assembly aggregation procedure as described above, and the chemically stabilized particles, CSA-H-DP, were recovered as before. Instrumentation and Product Characterization. The chemical composition of primary particles and aggregates was confirmed by FTIR spectroscopy as appropriate. The latter analyses were performed on a Perkin-Elmer 2400 analyzer and the former on a Perkin-Elmer 1600 series FTIR instrument using a diamond compression cell. The porous morphology of each aggregate was quantified by N2 sorption porosimetry using a Micromeritics ASAP 2000 gas adsorption instrument, and the data were manipulated using the software supplied with the instrument. Hg intrusion porosimetry data were acquired using a Micromeritics Autopore II 9220, and again the dedicated software was used to generate appropriate porosity parameters. For solvent stability testing, the appearance and characteristics of each aggregate, including shape and degree of integrity, were observed using an optical microscope. Each sample (0.05 g) was weighed into a series of small glass vials, to which a broad range of polar and nonpolar common solvents were added one to each vial. After a period of 4 days, the characteristics of the samples were re-assessed to give their relative stability in each of the solvents. Solvent uptake data for each aggregate using both toluene and n-hexane (as typical swelling and nonswelling solvents, respectively, for styrene-based resins) were determined gravimetrically and expressed as grams of solvent per grams of dry resin, using a sinter stick and centrifugation (3 min at 3000 rpm) to remove excess solvent.17 Aggregates were contacted with each solvent for 3 h to allow equilibrium to be attained prior to centrifugation. Scanning electron microscopic (SEM) analysis of aggregates was carried out on a JEOL 6400 scanning electron microscope operating at 10 kV. Samples were gold coated. Results and Discussion Synthesis of Monodisperse Primary Particles. Following some initial technique development, four samples of monodisperse primary particles were prepared via conventional free radical polymerization of appropriate vinyl monomers using surfactant-free emulsion (SFEP), precipitation (PP), and dispersion (DP) polymerization methodologies. Details of these are summarized in Table 1. Monodisperse particles (SFEP) were prepared successfully as a 33% solids aqueous emulsion as previously10 and have a diameter of ∼200 nm. These particles were to serve as a control for the self-assembly process (see later). Samples PP1-PP3 and DP were prepared by methodolo-

gies likely to yield monodisperse spherical particles with diameters around an order of magnitude larger than that of SFEP. In the event, the latter four samples were produced in good gravimetric yields and indeed with near monodisperse diameters of ∼5.0, 4.5, 1.0, and 1.5 µm, respectively. Attempts to self-assemble the primary particles PP2 and DP into larger particulates both failed (see later), and so these particles were hydrolyzed to convert the epoxy groups associated with the GMA segments into 1,2-diol functionalities. This was carried out using aqueous 5 M H2SO4, and the FTIR spectra of particles before (PP2 and DP) and after hydrolysis (H-PP2 and H-DP) suggest that the chemical modification is efficient with the appearance of a broad and intense H-bonded OH stretching vibration centered at 3400 cm-1. In each case, the content of oxygen (O wt % calculated as 100 - (C wt % + H wt %)) also increased from ∼20 to ∼26 wt %. Self-Assembly of Primary Particles into Larger Aggregates. Before proceeding to examine the self-assembly of the new primary particles, PP1-3, DP, H-PP2, and H-DP, the performance of the surfactant-free emulsion polymer SFEP was evaluated as a control. The inverse suspension procedure used was as we have previously reported.9 The 33% solids aqueous emulsion was dispersed as droplets in toluene with the stability of the dispersion aided by the use of the low HLB non-ionic surfactant sorbitan monooleate (Span 80). The water was then removed from the aqueous emulsion phase by azeotropic distillation with some of the toluene. As previously reported, solid spherical self-assembled aggregates (A-SFEP, ∼10-30 µm in diameter, Figure 1, left) were recovered in good yield. (Note that in this case the ∼200 nm primary particles are not resolved in the SEM at ×1100, Figure 1, right.) These aggregates were subsequently chemically modified to improve their stability (see later). Turning to the precipitation polymerization primary particles PP1 that have a very similar commoner composition but that have a much larger diameter (∼5 µm), a dry sample was added to water to yield a 33% solids dispersion similar to that used in the case of SE, and the inverse suspension self-assembly procedure was carried out as before. In this case, no aggregates were formed; instead, the primary particles were recovered unchanged. A simple visual examination in a test tube of a PP1 sample dispersed in water, and the suspension shaken with toluene, showed that most of the sample remained in the aqueous phase, although a much smaller fraction did migrate into the toluene phase. This suggested that the charge density (due to the carboxylic acid groups) on the surface of the PP1 particles might be rather lower than it was on the SFEP particles, and the tendency for the PP1 particles to migrate to the toluene phase might explain the failure of the self-assembly process. Converting the carboxylic acid groups to sodium carboxylate groups indeed reduced the tendency for the PP1 particles to migrate to the toluene phase in the test tube experiment. However, the self-assembly process failed again when this was repeated, and the failure seemed to be attributable simply to the relatively large size of the PP1 particles, which are ∼25 times larger than the SFEP primary particles. This conclusion was reinforced in the case of the PP2 primary particles (Figure 2, left), which likewise failed to produce self-assembled aggregate particles. These primary particles have a structural composition different from those of SFEP and PP1, and so the explanation for the failure may be different in this case, but it does seem that that the larger primary particle size, 4.5 µm, does at least contribute to the failure of the self-assembly process. Furthermore, hydrolysis of PP2 to convert its epoxide groups into diol functionalities, which was achieved without

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Figure 1. SEM (×40 and ×1100) of self-assembled aggregates of SFEP primary particles. Note that the individual ∼200 nm primary particles are too small to be resolved even at ×1100.

Figure 2. SEM images (×1500) of (left) PP2 primary particles (∼5 µm) and (right) H-PP2 hydrolyzed sample.

Figure 3. SEMs (×20, ×1300, ×2500) of self-assembled aggregates A-PP3 of primary particles PP3.

compromising the integrity of the particles (H-PP2, Figure 2, right), and attempted self-assembly of the latter also failed to produce any stable aggregates, reinforcing the view that the large size of these particles is the main limiting factor. In the case of PP1, an extensive number of experimental variants of the self-

assembly procedure were examined, and in no case were any aggregates recovered. Suspecting that a primary particle size of ∼5 µm was beyond the mechanical limit to allow a self-assembly process to yield stable aggregates, the primary particles PP3 with a diameter of

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Figure 4. SEMs (×20, ×500, ×2300) of self-assembled aggregates A-H-DP of primary particles H-DP. Table 2. Solvent Stability Data for Self-Assembled Aggregate Particles Prior to and Post-Stabilizationa stability of self-assembled aggregate

a

solvent

A-SFEP

CS-A-SFEP

A-PP3

CS-A-PP3

A-H-DP

CS-A-H-DP

heptane hexane toluene diethyl ether dichloromethane tetrahydrofuran acetone methanol ethanol acetonitrile dimethylformamide water

Y Y Y Y Y D Y/N Y N Y D Y

Y Y Y Y Y Y Y Y Y Y Y Y

Y Y Y Y Y Y Y/N Y/N N N Y/N Y

Y Y Y Y Y Y Y Y Y Y Y Y

Y Y Y Y Y Y/N Y/N Y/N Y/N Y/N Y/N Y

Y Y Y Y Y Y Y Y Y Y Y Y

Y ) stable; N ) disintegrates; Y/N ) fissures appear on surface; D ) dissolves.

∼1 µm were examined using the standard inverse suspension procedure. In this case, self-assembled aggregates (A-PP3) were formed and were readily recovered and dried. Although the aggregates are not as regular as we have seen with the A-SFEP aggregates, the SEM images of A-PP3 at magnification 1300 (Figure 3, middle) show a rather attractive self-assembled array of PP3 primary particles. The shape of most aggregate particles is roughly spherical with diameters in the range 0.05-1.0 mm. A particle with a diameter of ∼60 µm would therefore contain ∼60 primary particles across a diameter if these were regularly close-packed. This seems to be approximately the case, but the rather irregular packing and the presence of significant fissures are apparent in the SEM images of A-PP3 (Figure 3, middle). The comonomer composition of the precursor particles PP3 is MAA/DVB ) 60/40, whereas that of PP1 is MAA/DVB ) 25/75. This difference results first in the primary particles produced in the precipitation polymerization being smaller, ∼1 versus ∼5 µm, but the higher surface charge density of these probably also contributes interfacially to the success of the selfassembly process in conjunction with the smaller size of these particles. The importance of the carboxylic acid groups in the self-assembly process tends to be confirmed by the failure of the dispersion polymerized particles DP to successfully selfassemble despite being of size similar to that of PP3 (i.e., ∼1.5 µm). The DP particles have epoxy groups present from the GMA comonomer, but they lack any carboxylic acid functions. This raised the interesting question “if the epoxide functionality were to be hydrolyzed to the corresponding diol, would the presence of the diol groups aid the self-assembly process?” Indeed, the hydrolyzed DP particles (H-DP) do self-assemble

under the standard inverse suspension conditions to yield near spherical particles (A-H-DP) (Figure 4) with a density of packing similar to that displayed by the A-PP3 aggregates. Thus, it seems that two criteria are required for successful selfassembly. The first is that the primary particles must have a diameter of ∼1 µm or smaller, and the second is that the particles must have a sufficiency of hydroxylic groups (i.e., hydroxyl or carboxylic acid functions). Stability of Self-Assembled Aggregate Particles. One of the potential applications of self-assembled aggregate particles such as A-SFEP, A-PP3, and A-H-DP is as the basis of novel stationary phases in column separations or sorbents in batch separations involving aqueous or organic solutions. It is therefore crucial for these particles to remain chemically stable and physically intact in the working solvent. In previous work with the self-assembled aggregates A-SFEP,9 we have shown that these are stable in rather nonpolar solvents such as dichloromethane, hexane, and toluene (note that this is the organic phase in which the self-assembly procedure is carried out) but also in polar protic solvents such as water and methanol. However, they tend to fragment in solvents of intermediate polarity such as acetone and ethanol and indeed dissolve to some extent in specific solvents (tetrahydrofuran and dimethylformamide) (see Table 2). The observed stability behavior is rather difficult to understand bearing mind that the polymer chains constituting each SFEP particle are linear species with broad solubility properties, and in addition the self-assembly process does not involve any designed particle fusion chemistry. However, from earlier SEM evidence, it seems that the thermal treatment associated with the Dean-Stark distillation procedure

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Ind. Eng. Chem. Res., Vol. 46, No. 10, 2007 Table 3. Dry-State Porosity and Solvent Uptake Data for Self-Assembled Particles solvent uptake (g g-1) sample

toluene

n-hexane

A-SFEPa CS-A-SFEP CS-A-PP3 CS-A-H-DP

n/R 0.6 0.5 0.5

0.2 0.1 0.3 0.3

9-16 9 (55b)