Narrow Polydispersity Cross-Linked Microparticles

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Monodispersity/Narrow Polydispersity Cross-Linked Microparticles Prepared by Step-Growth Thiol−Michael Addition Dispersion Polymerizations Chen Wang,† Xinpeng Zhang,† Maciej Podgórski,†,‡ Weixian Xi,† Parag Shah,† Jeffery Stansbury,†,§ and Christopher N. Bowman*,† †

Department of Chemical and Biological Engineering, University of Colorado, UCB 596, Boulder, Colorado 80309, United States Faculty of Chemistry, Department of Polymer Chemistry, MCS University, Marii Curie-Skłodowskiej, 20-031 Lublin, Poland § Department of Craniofacial Biology, School of Dental Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, United States ‡

ABSTRACT: We report a dispersion polymerization method based on thiol−Michael addition reactions for the preparation of cross-linked, narrow dispersity microparticles with well-defined, tunable physicochemical properties. Polymerization between pentaerythritol tetra(3-mercaptopropionate) (PETMP) and trimethylolpropane triacrylate in methanol was chosen as a model system, with the addition of triethylamine as a catalyst and polyvinylpyrrolidone as a stabilizer. The formation of microparticles took place within seconds at ambient conditions, as a result of a polymerization driven phase transition from dissolved monomers to precipitated polymers. The particle size was found to be affected by the amount of catalyst, the monomer concentration, and the monomer/polymer solubility in the reaction media. Monodispersity was achieved within a range of particle diameters from 1.6 to 4.3 μm, as determined both by scanning electron microscopy and dynamic light scattering. The reaction kinetics were studied by Fourier transform infrared spectroscopy by analyzing aliquots withdrawn from the reaction system at various reaction time points. Nearly quantitative conversions were achieved within 6 h for stoichiometric systems and 1 h for off-stoichiometric systems, both initiated with triethylamine. By utilizing photolabile bases as the reaction catalyst, phototriggered formation of the microparticles was demonstrated with ultraviolet irradiation. Monodisperse particles were formed with hexylamine and 1,1,3,3-tetramethylguanidine, both with 2-(2-nitrophenyl)propyloxycarbonyl as the UV-labile photocage. Furthermore, as a demonstration of the versatility of this method, microparticles were prepared from copolymerizations between PETMP and four types of diacrylates with varied backbone structures. With increased backbone rigidity, the microparticle glass transition temperature increased from −36 to 8 °C. This method provides a platform for the realization of the nearly ideal step-growth networks in microscale, with highly tunable backbone structures, robust thermal transitions, and intrinsic functionalization capacity.

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INTRODUCTION For decades, polymeric microparticles have drawn significant attention in both industry and academia due to their wide-scale implementation in resins,1 latexes,2,3 cosmetic products,4,5 biomedicines,6−8 and many others. In particular, monodisperse microparticles are targeted for unique applications including chromatography,9,10 photonic crystals,11−14 and colloidal molecules.15−19 A variety of techniques have been developed to prepare microparticles with uniform morphologies, such as utilizing microfluidic devices,20,21 block copolymer selfassembly,22,23 and polymerization strategies,24 which include but are not limited to suspension, emulsion, and dispersion polymerizations. Among these techniques, dispersion polymerization has become a widely used method for facile and efficient preparation of microparticles, as originally introduced by Keith Barrett in the 1970s.25 In dispersion polymerization, particles are formed by a smooth phase transition (from homogeneous to heterogeneous phases) during the polymerization, which © XXXX American Chemical Society

involves no additional energy/cost to stabilize the multiphases dispersions, as opposed to the intense homogenization or emulsification processes required in suspension and emulsion polymerizations. Since then, research has been mainly focused on implementation of various radical-mediated chain-growth polymerizations, including the preparation of styrenic and (meth)acrylic polymers26−28 as well as their copolymers with various functional monomers.29−33 Following the development of reversible deactivation radical polymerizations, dispersion polymerization methods have received renewed attention,34−37 especially in the investigation of polymerization-induced selfassembly.38,39 For example, amphiphilic block copolymers that were prepared from reversible addition−fragmentation chain transfer polymerization (RAFT) in aqueous systems were Received: September 29, 2015 Revised: November 11, 2015

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DOI: 10.1021/acs.macromol.5b02146 Macromolecules XXXX, XXX, XXX−XXX

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“click” reactions; and (iii) tunable backbones, for example with ester-containing particles for degradation and corresponding cargo release. Herein, we investigate the effects of polymerization conditions on the formation of microparticles, including variations in monomer loadings, reaction media, and reaction extents. The photoinitiation of the thiol−Michael dispersion polymerization is also demonstrated.

shown to undergo thermodynamically favored or kinetically trapped phase transitions and subsequently in situ assembled into nano-objects including spherical, tubular, and vesicular structures.40−42 However, to date, step-growth dispersion polymerizations have been received limited attention, often associated with the inefficiency of many condensation reactions under dilute conditions. Also, many reagents employed in step-growth polymerizations such as acyl chlorides, isocyanates, and carboxylic acids are intolerant to alcoholic and/or aqueous media, in which dispersion polymerizations are commonly conducted. Such limitations contribute largely to the scarce implementation of step-growth polymers in colloidal materials, in dramatic contrast to their prevailing importance in numerous other materials’ applications. Step-growth polymerizations and polymers encompass a broad variety of materials that enable highly tunable polymer backbones and side chains and facilitate the preparation of functional, degradable, stimuli-responsive, and high-performance polymers. Cross-linked step-growth polymers often form nearly ideal networks, which have been reported to be advantageous over their chain-growth counterparts, at least in part because they enable robust transitions and intrinsic functionalization by off-stoichiometric polymerizations.43 To implement step-growth polymerizations in dispersion systems, reactions that are rapid and efficient in heterogeneous systems must be used. Recently, the utilization of “click” reactions for step-growth polymerizations has gained emerging research interest, including azide−alkyne cycloaddition44−49 and thiol−X reactions.43,50−52 The “click” attributes, including the high efficiency and yield under mild conditions, render these reactions ideal candidates for polymer synthesis.53,76 Furthermore, these reactions are highly tolerant to many polar solvents and thus enable practices in dispersed systems. In one example, Du Prez et al.54 demonstrated thiol−ene/yne polymerizations in microfluidic devices for the preparation of functional particles with diameters of hundreds of microns. Shipp et al.55−57 reported several cases of thiol−ene/yne suspension polymerizations, while Pojman et al.58,75 showed a thiol−Michael addition suspension polymerization between multithiols and multiacrylates. Also, in emulsion polymerization systems, lightinitiated thiol−ene/yne polymerizations have been studied by Chemtob et al.59 and Patton et al.60 Compared with radical mediated thiol−ene/yne reactions, the absence of radicals in thiol−Michael addition reactions is enabling for several aspects in the preparation of functional materials. Functional groups that are vulnerable to radicals are unaffected in thiol−Michael addition conditions, for example, (meth)acrylates. We recently reported a thiol−Michael addition miniemulsion polymerization for the preparation of functional nanoparticles.61 The latex films prepared by drying those nanoparticles retained reactivity and promoted facile surface modification as well as a second stage photocuring that could be used to achieve enhanced mechanical performance. In a previous report,62 we demonstrated the preparation of monodisperse microspheres by a thiol−Michael addition dispersion polymerization. This work for the first time realized step-growth polymer networks in uniform microscales structures, with three of the following advantages demonstrated: (i) uniform network structures, i.e., particles with narrow glass transitions for implementations in polymeric composites; (ii) intrinsically functionalized networks composed of particles with “clickable” groups for fluorescent labeling by

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EXPERIMENTAL SECTION

Materials. Pentaerythritol tetra(3-mercaptopropionate) (PETMP) was donated by Bruno Bock. Glycol di(3-mercaptopropionate) (GDMP) was purchased from Wako Chemicals. Divinyl sulfone (DVS) was purchased from Oakwood Products. Trifluoroacetic acid (TFA), triethylamine (TEA), polyvinylpyrrolidone (K-value 29−32, average Mn 40 000) (PVP), trimethylolpropane triacrylate (TMPTA), tricyclo[5.2.1.02,6]decanedimethanol diacrylate (TCDDA), neopentyl glycol diacrylate (NPDA), 1,6-hexanediol diacrylate (HDDA), tetraethylene glycol diacrylate (TEGDA), and trimethylolpropane tri(3mercaptopropionate) (TMPTMP) were purchased from SigmaAldrich and used as received. The NPPOC-hexylamine and NPPOC-TMG photobases were synthesized as reported elsewhere.63,64 General Procedure of Microsphere Preparation. The model system involves a solution of 3.66 g of PETMP, 2.98 g of TMPTA, and 1.5 g of PVP in 150 mL of methanol. A catalyst, i.e. 0.33 g of TEA, was added to the solution under 400 rpm overhead mechanical stirring, and the solution turned turbid subsequently. The mixture was kept under stirring for 6 h, and the product was harvested by a centrifuge and washed with 100 mL of methanol for three times. Procedure of Photoinduced Microsphere Preparation. UV irradiation was conducted by an EXFO Acticure 4000 lamp equipped with a 320−390 nm light filter. A 1.5 mL solution of PETMP, TMPTA, photobase, and PVP in methanol was prepared in a drum vial. The mixture was kept under magnetic stirring and was subsequently exposed to UV light through an optical fiber. The light intensity was measured to be 100 mW/cm2 at 365 nm by a calibrated IL1400-A radiometer from International Light Technologies Inc. After irradiation, an opaque dispersion was obtained, and the product was purified by a centrifuge and washed in methanol for three times. Characterization. Scanning electron microscopy (SEM): the morphology of microspheres was observed on a JEOL SEM 7401F field emission scanning electron microscope. A SEM sample was made by casting a dispersion of microspheres in methanol onto a glass slide. The sample was subsequently dried and coated with a thin layer of gold before imaging. A minimum random sample of 50 microspheres was analyzed from a SEM image to determine the average particle diameter. The coefficient of variance (CV) was determined by N

CV% =

∑i = 1 (di − dn̅ )2 dn̅

× 100

where di is the diameter for each microparticle and dn is the average diameter. Fourier transform inf rared spectroscopy (FTIR): a diffuse reflectance setup on a Thermo Nicolet 6700 was used for powder samples. Samples were prepared by mixing microparticle dispersions with KBr and subsequently dried to remove residual solvent. Peak areas of peaks centered at 2570 and 810 cm−1 were used to monitor the consumption of thiol and acrylate functional groups, respectively. Dif ferential scanning calorimetry (DSC): the glass transition temperatures of microparticle samples were characterized on a Diamond DSC (PerkinElmer). An indium standard was used for calibration. In hermetically sealed aluminum pans, samples underwent two heating cycles between −50 and 150 °C at a ramping rate of 10 °C/min. The glass transition temperature was determined from the second heating cycle. Dynamic light scattering (DLS): the DLS measurements for the size and size distribution of microspheres were performed on a Brookhaven particle size analyzer. A dilute dispersion of particles in B


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Macromolecules methanol was used for each test. Each collection was carried out for 3 min, and the results were averaged from three separate collections. Gel permeation chromatography (GPC): the polymer molecular weights were determined by a Tosoh EcoSEC GPC system (HLC8320) with DMSO as the mobile phase at a flow rate of 0.350 mL/min at 50 °C. Column sets: two TSKgel SuperHM-H, 3 μm, 6.0 mm i.d. × 15 cm columns. Molecular weights were calculated based on a calibration with narrow polydispersity poly(methyl methacrylate) standards.

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RESULTS AND DISCUSSION The reaction scheme for the thiol−Michael addition dispersion polymerization is depicted in Scheme 1. We chose a Scheme 1. General Scheme for the Thiol−Michael Addition Dispersion Polymerizationa

Multithiols and multiacrylates undergo stoichiometric anion-mediated Michael addition polymerizations in methanol, triggered by adding a base or photobase with irradiation. A phase transition occurs shortly after the initiation, and the precipitated cross-linking polymer forms uniform microparticles. The reaction proceeds completely within hours at ambient temperature under appropriate conditions.

Figure 1. Size and size distribution for microspheres made by a dispersion polymerization of a stoichiometric 1:1 mixture of thiol:acrylate functional groups (PETMP−TMPTA) in methanol. (A) Scanning electron microscopy images and (B) diameter distribution obtained from dynamic light scattering. Polymerization conditions: stoichiometric PETMP and TMPTA were allowed to react for 6 h in methanol (5.6 wt % monomers) at ambient temperature under 400 rpm overhead stirring.

combination of a tetrathiol and a triacrylate as our model monomers, namely pentaerythritol tetra(3-mercaptopropionate) (PETMP) and trimethylolpropane triacrylate (TMPTA), respectively. Both PETMP and TMPTA are aliphatic multiesters; therefore, we initially employed a typical dispersion polymerization condition commonly used for poly(methyl methacrylate) (PMMA), which includes polyvinylpyrrolidone (PVP) as the stabilizer and methanol as the reaction media.65 For the model system that is described in the Experimental Section, the morphology and size distribution of the microspheres are shown in Figure 1. In Figure 1A, a monolayer of microspheres deposited on a glass slide was imaged by scanning electron microscopy (SEM). The microspheres are uniform in size with an average diameter of 2.41 μm and a coefficient of variance of 5.4%. The particle size was also measured by dynamic light scattering (DLS), as shown in Figure 1B. The average diameter measured by DLS is slightly larger than that from SEM, probably due to swelling of the particles in the solvent. The size distribution from DLS is very narrow, indicating monodispersity, which is consistent with the SEM images. The highly cross-linked particles were readily

dispersed and remained insoluble in most organic solvents, while they flocculated in water due to their hydrophobicity. According to the Flory−Stockmayer equation, the gel point conversion for an ideal stoichiometric PETMP−TMPTA mixture is 40.8%. Even for largely off-stoichiometric systems, for example, for a 2:1 thiol:acrylate ratio, the gel point conversion is estimated to be 57.7%. Given the nearly quantitative conversion in Michael addition between thiols and acrylates, the PETMP−TMPTA system enables the design of largely off-stoichiometric systems while maintaining the ability to form polymer networks. Since the reaction conversion is critical to network formation, we studied the conversion evolution during polymerizations of both stoichiometric and off-stoichiometric systems. Kinetics of Particle Formation. In chain-growth dispersion polymerizations, the reaction extent is readily determined by fractionating the particles and the remaining unreacted monomer, which is usually determined simply by gravimetric analysis, 1H NMR, or gas chromatography. However, those methods are not applicable for cross-linking

a

C


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conversion. The conversion at 1, 10, 90, and 330 min was assessed to be 53%, 84%, 98%, and 99%, respectively. It is worth noting that the reaction mixture turned opaque within 10 s upon the addiiton of TEA, and the conversion at 1 min of reaction was already higher than the theoretical gel point. Thus, the formation of microscale polymer networks was very rapid. Later on, the consumption of the remaining thiol and acrylate decreased significantly. However, nearly quantitative conversion was achieved within 6 h of continuous stirring and reaction. The decline in the reaction rate is because of a decreased concentration of reactants. Also, it could be caused by the limited diffusion of reactants within the already cross-linked polymer particles. In contrast, for chain-growth dispersion polymerizations, the reaction kinetics are similar to solution polymerizations because the reaction happens predominately in the solution while very little reaction happens in the solid phase. Typically, the chain growth reaction rate reaches a maximum rapidly, and then it decays as a result of the lowered monomer concentration. Further, it is extremely difficult for the polymerization to reach quantitative conversion due to the inefficiency of radical polymerizations in dilute conditions. In chain-growth dispersion polymerizations, a “critical length” of propagating polymer is required for precipitation to occur. For PMMA the critical length is reported to be 100− 200 repeating units in a methanol/water mixture (70/30 w/ w).66 To understand the phase transition for step-growth dispersion polymerization, we studied the molecular weight of the formed polymer as close as possible to when the precipitation occurs. To do so, the model reaction between PETMP−TMPTA was quenched with excess trifluoroacetic acid (TFA) right after the reaction became turbid. After removing all the volatiles under vacuum, the polymer was insoluble in organic solvents such as acetone, THF, and DMSO. This indicates that cross-linking occurs in the early precipitation step. Similar phenomena were found for systems of lower cross-linking densities. The polymerization between a trithiol (trimethylolpropane tri(3-mercaptopropionate), TMPTMP) and TMPTA was carried out under similar conditions. The reaction mixture required minutes to reach the precipitation level, and the polymer obtained after quenching reaction was insoluble. Further, the polymerization between a dithiol glycol di(3-mercaptopropionate) (GDMP) and TMPTA showed a more delayed phase transition while the polymer was again insoluble. Finally, we studied a linear analogue where an equal molar mixture of 1,6-hexanediol diacrylate (HDDA) and GDMP underwent polymerization in methanol. For this system, precipitation was observed approximately 1 h after the start of the reaction, and the precipitated polymer was analyzed by GPC. The molecular weight showed a Flory−Schulz distribution, with an average Mn of 1300 Da and a PDI of 4.2, indicating that the precipitation happened at the late stage of the polymerization. In chaingrowth polymerizations, the molecular weight is proportional to the kinetic chain length, which in most cases reaches the highest value shortly after the beginning of the polymerization. As a result, the substantial change of solubility that leads to phase separation in dispersion polymerizations happens at an extremely low conversion. However, in step-growth polymerizations since the polymer length increases gradually with respect to the reaction extent prior to the gel point, there is a less dramatic change in solubility. On the other hand, crosslinking would tremendously facilitate the precipitation process in that cross-linked polymers are insoluble by their nature. We

step-growth polymerizations. In step-growth systems, oligomers/polymers contain a large amount of unreacted species so that the disappearance of monomer cannot be used to indicate full conversion. For cross-linking polymerizations in dispersion systems, the amount of remaining monomers in solution does not represent the reactive functional group conversion because unreacted functional groups can and do also exist within the solid phase. In fact, since the gelation of PETMP−TMPTA system happens at less than 50% conversion, the consumption of reactants on the particles is not negligible but rather significant. Thus, we chose FT-IR spectroscopy as a convenient method to determine the conversion since there would not be bias between solid and liquid phases. At first trials we faced some difficulties in measuring the conversion by FT-IR in transmission mode due to the weak IR signal resulting from the turbid microparticle dispersions. Though near-IR has been used for in situ measurement of opaque miniemulsion polymerization systems, the particle diameters are typically in the range of 50−200 nm, and hence they do not diffract the light as much as microparticles do.59 Ultimately, we chose diffuse reflectance FT-IR and carried out the tests on powder samples. Aliquots were withdrawn from the reaction mixture at various times and were subsequently mixed with KBr and dried. The dried mixture was sampled immediately for an accurate representation of the ongoing reaction. Both PETMP and TMPTA are not volatile, so only methanol was removed during drying. For a stoichiometric PETMP−TMPTA system, the reaction scheme and the evolution of the IR signals are shown in Figure 2. The peak area in the range of 2470−2600 cm−1 was used for quantifying the thiol amount while that at 795−810 cm−1 was used for the acrylate. The broad peak from 2800 to 3000 cm−1 was used as an internal reference peak to eliminate the variations of IR absorbance between powder samples, and the spectrum for the unreacted mixture was used to determine the

Figure 2. Reaction scheme and FT-IR spectral time evolution series of a thiol−Michael addition polymerization of stoichiometric PETMP− TMPTA at different reaction times. Polymerization conditions: 3 wt % PETMP and 2.5 wt % TMPTA were dissolved in methanol (0.2 mol/L of both thiol and acrylate functional groups), with 15 wt % PVP with respect to the total of monomers. The reaction was initiated with 10 wt % TEA (with respect to monomer content). D


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microspheres which contain residual vinyl groups for postpolymerization modification reactions,73,74 herein we believe these intrinsically functionalizable microspheres can be used as versatile scaffolds for a variety of applications. Effect of Monomer Concentration. In our previous report, we have demonstrated that the diameter of particles decreases significantly with the functionalities of the monomers used as well as the loadings of the initiator. In the following, the effects of other polymerization conditions are assessed, such as monomer concentration and the types of reaction media. In chain-growth dispersion polymerizations, the particle size is typically proportional to the monomer concentration. For example, the diameter of polystyrene microparticles increases from 2.5 to 6.2 μm in ethanol with an increased monomer loading from 12.5 to 37.5 wt %.27 Herein, we carried out a series of polymerizations of stoichiometric PETMP and TMPTA with varied concentrations in methanol, while all the other reaction conditions remained unaltered. When the monomer loading increased from 1.4 to 11.2 wt %, the particle size increased dramatically, as shown in Figure 4. Quantita-

noticed that the occurrence of precipitation was later than the gel point for all cross-linking systems; also for the linear system the precipitation happened at later stages of the polymerization. Thus, we conclude that the phase transition is mainly a result of the cross-linking that occurs in the thiol−Michael addition dispersion polymerization between PETMP and TMPTA. The polymerization kinetics in the off-stoichiometric systems were also studied. The FT-IR spectra for both thiol-excess and acrylate-excess reactions are shown in Figure 3. The solubility

Figure 3. FT-IR spectra series for off-stoichiometric thiol−Michael addition dispersion polymerization between PETMP−TMPTA. (A) Thiol excess: 6.1 wt % PETMP and 2.5 wt % TMPTA in methanol/ acetone mixture (90/10 v/v, 0.4 mol/L of thiol and 0.2 mol/L of acrylate functional groups). (B) Acrylate excess: 3.0 wt % PETMP and 5.0 wt % TMPTA in methanol (0.2 mol/L of thiol and 0.4 mol/L of acrylate functional groups). Both of the polymerizations were initiated with 10 wt % TEA (with respect to the sum of the limiting reactant and its stoichiometric amount of coreactant).

Figure 4. SEM images of microspheres prepared from various loadings of stoichiometric PETMP and TMPTA in methanol: (A) 1.4, (B) 2.8, (C) 4.2, (D) 7.0, (E) 8.4, and (F) 11.2 wt % monomer. Polymerization conditions: monomers were dissolved with 1.5 g of PVP in 150 mL of methanol; 0.32 g of TEA was used for initiation, and the reaction was allowed for 6 h.

of PETMP in methanol was found to be up to 3 wt %. To dissolve 6.1 wt % PETMP, acetone was used as a cosolvent with methanol (acetone:methanol = 1:9, v/v). As shown in Figure 3A, the acrylate conversion reached 81%, 97%, and 100% at 1, 10, and 60 min, respectively, and the final thiol conversion was measured to be 39%. On the other hand, in Figure 3B, the thiol conversion reaches 78%, 93%, and 97% at 1, 10, and 60 min, respectively, while the final acrylate conversion was found to be 55%. Compared with the stoichiometric polymerization, both the polymerizations with excess species proceeded more rapidly. The species in excess showed conversions that were close to 50%, despite small discrepancies with theoretical values probably due to the limited accuracy of the diffuse reflectance FT-IR measurements. It is worth noting that both the thiolexcess and acrylate-excess particles were stable during purification steps and could be easily redispersed, which enables further modification, functionalization, or covalent integration into composites. Similar to polydivinylbenzene

tively, the variance in average diameter and coefficient of variance (CV) for these samples are shown in Figure 5A. The average diameters for polymerizations with 1.4, 2.8, 4.2, and 5.6 wt % monomer are 1.66, 2.03, 2.14, and 2.41 μm, respectively. The average diameters increase linearly with monomer loadings, with good monodispersity as CVs were no higher than 5%. However, particle sizes increased dramatically with monomer loadings higher than 7 wt %. With 8.4 and 11.2 wt % monomer, the average diameters were found to be 5.16 and 10.9 μm, respectively, both with accompanying CVs higher than 20%. This behavior implies an instability of large microparticles causing nonuniform aggregations of particles, which resulted in significant variations in particle size. We calculated the number density of particles based on particle sizes and monomer loadings. By assuming that E


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propagating particles brings inconsistencies in size which may lead to nonuniformity in the final product. Effect of Polymerization Media. Since the particles are generated in a process of a phase transition from a homogeneous solution to a solid/liquid dispersion, the solubility of the reaction media is expected to influence the particle formation. It has been reported that for the formation of monodisperse microparticles the solubility of the solvent must be within a particular range, which varies according to the monomers used.68 In other words, the media for dispersion polymerizations are “marginal solvents” and the “margin” is usually quite narrowsolubilizing the monomers but not oligomers of some critical size.69 We found that methanol dissolves only up to 3 wt % PETMP so that methanol is in the low range for the PETMP−TMPTA system. Then, the solubility was increased by mixing with acetone, as acetone dissolves both monomers well. Figure 6 shows the SEM images

Figure 5. (A) Average diameters and coefficients of variance of microspheres prepared with increasing monomer loadings. (B) Number densities of particles as a function of monomer loading. Polymerization conditions: monomers are dissolved with 1.5 g of PVP in 150 mL of methanol with the addition of 0.32 g of TEA that was reacted for 6 h. Figure 6. SEM images of microspheres prepared from stoichiometric PETMP and TMPTA in mixed solvents of methanol and acetone with various compositions. Acetone volume concentrations: (A) 6.6, (B) 13.3, (C) 26.7, and (D) 33.3 vol %. Polymerization conditions: 3.66 g of PETMP and 2.98 g of TMPTA were dissolved with 1.5 g of PVP in 150 mL of mixed solvents; 0.32 g of TEA was used for initiation, and the reaction was carried out for 6 h.

quantitative yields are achieved, the number density of particles can be determined by n=

N ω ω = = 4 3 V m ρ 3 πr̅

where n is the number of particles per unit volume, N is the total number of particles, V is the volume, ω is the weight concentration of particles, m is the mass of an individual particle, r ̅ is the average radius of particles, and ρ is the density of particles, which is estimated to be 1.2 g/mL since the densities for PETMP and TMPTA are 1.28 and 1.1 g/mL, respectively. Figure 5B shows the number density of particles with respect to monomer loading. At low monomer loadings, the number densities were found to be constant near 6 × 1012 per milliliter in methanol. However, at high monomer loadings, the number densities dropped dramatically, down to 1 × 1011 per milliliter for 11.2% monomer. In dispersion polymerizations, the number of particles is typically determined during the nucleation stage, which is demonstrated to be sensitive to the variations in the reaction conditions.67 After the nucleation stage, the particle size increases steadily but the number remains constant. The dramatic reduction in the number of particles has to be caused by the interparticle reactions at an early stage of the polymerization, which has higher chances to occur at higher monomer loadings. Also, such a coagulation between

of microparticles prepared from mixtures of methanol and acetone with different volume ratios of the good (acetone) and poor (methanol) solvents. As the volume fraction of acetone increased from 0% to 20%, the average diameters increased from 2.41 to 6.51 μm (Figure 6A−C), with CVs increasing from 5% to 29%. When the acetone fraction was 33.3%, irregularly shaped particles were formed (Figure 6D) probably because some of the polymers remained dissolved in the solvent mixture. The particle sizes and number densities are summarized in Figure 7. The number densities showed a consistent decrease from 9 × 1012 to 3 × 1011 as the fraction of acetone increased from 0% to 27%. The improved solubility required a longer critical length or a higher degree of branching/cross-linking for the initial precipitation to occur. In dispersion polymerizations of polystyrene or PMMA, monodispersity can be achieved in mixed solvents with various ratios, such as ethanol/water, acetonitrile/hexane, and acidic acid/methyl ethyl ketone. However, for the PETMP−TMPTA system even with a small amount of acetone added, the size F


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Figure 7. Average diameters and number densities of microspheres prepared from mixed solvents of methanol and acetone with varied solvent quality and composition. Polymerization conditions: 3.66 g of PETMP and 2.98 g of TMPTA were dissolved with 1.5 g of PVP in 150 mL of mixed solvents; 0.32 g of TEA was used as the initiator, and the polymerization was carried out for 6 h.

Figure 8. FT-IR spectra for photoinitiated thiol−Michael addition dispersion polymerization for acrylate-excess PETMP−TMPTA systems. Reaction conditions: 3.0 wt % PETMP and 5.0 wt % TMPTA in methanol (0.2 mol/L of thiol and 0.4 mol/L of acrylate functional groups); 20 wt % PVP and 20 wt % photobase were added (both with respect to monomers). Irradiation conditions: a UV lamp equipped with 320−390 nm filter, and the intensity was measured to be 100 mW/cm2 at 365 nm; an optical fiber was used to keep the sample away from the lamp to avoid heating. For NPPOC-hexylamine, a total of 1 h of irradiation was applied. For NPPOC-TMG, the reactants were irradiated for 15 min.

distribution is affected. Since the polymerization involves at least two types of monomers and many species of oligomers, i.e., branched and partially cross-linked polymers, we conclude that a step-growth dispersion polymerization is likely to be more sensitive to the reaction media than its chain-growth comparison. Therefore, the reaction conditions have to be optimized to obtain monodispersity. Photoinitiated Dispersion Polymerization. Photoinitiation of dispersion polymerization has been reported for conventional and controlled radical polymerizations of styrenic, acrylamidic, and methacrylic monomers.70,71 Photoinduced processes enable a reaction with precise spatial and temporal control, which expands its utilization for a variety of materials science applications. Also, the reaction rate can be conveniently adjusted simply by changing the irradiation intensity. In our research group, we have developed a series of 2-(2-nitrophenyl)propyloxycarbonyl (NPPOC) caged amines for efficient photoinitiation of the thiol−Michael addition reactions.63,64 To demonstrate photoinduced microparticle formation, initially we used NPPOC-hexylamine in the replacement of hexylamine for the acrylate-excess PETMP−TMPTA model system. In a total of 1.5 mL of methanol solution, 3.0 wt % PETMP and 5.0 wt % TMPTA were dissolved in the presence of 20 wt % PVP and 20 wt % NPPOC-hexylamine (both with respect to monomers). Originally the reaction mixture was a clear colorless solution. No phase transition was observed until irradiation with 320− 390 nm UV light (100 mW/cm2 at 365 nm) was applied, and the reaction mixture subsequently turned turbid. Aliquots were taken for FT-IR measurement to monitor the reaction extent. Complete disappearance of the thiol groups was found after 1 h of continuous irradiation, as shown in Figure 8. The thiol− Michael addition kinetics were greatly improved when a photolabile superbase, i.e., TMG, was used. The polymerization with NPPOC protected 1,1,3,3-tetramethylguanidine (NPPOC-TMG, 20 wt % to monomers) showed complete thiol conversion within 15 min of irradiation. Figure 9A shows the optical microscopy images of particles by using NPPOChexylamine and irradiation, which were of 2.5 μm in diameter and monodisperse. For comparison, particles prepared by directly adding 6.5 wt % hexylamine (equal molar to 20 wt % NPPOC-hexylamine) are shown in Figure 9B, while the other reaction conditions remained unchanged. Monodispersity was achieved in both cases; however, the photoinduced particles

Figure 9. Optical microscope images for PETMP−TMPTA microparticles formed by (A) NPPOC-hexylamine and UV irradiation under 100 mW/cm2 at 365 nm for 1 h. (B) Adding an equimolar amount of hexylamine as compared to NPPOC-hexylamine. Reaction conditions: 3.0 wt % PETMP and 5.0 wt % TMPTA in methanol (0.2 mol/L of thiol and 0.4 mol/L of acrylate functional groups), 20 wt % PVP and 20 wt % NPPOC-hexylamine or 6.5 wt % hexylamine were used (all with respect to monomers).

were larger than their conventionally initiated counterparts. As the hexylamine is released gradually with respect to the irradiation dose, the actual amount of hexylamine that catalyzes G


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Macromolecules the reaction is less than the control case. This behavior is consistent with our previous observation that the particle size increases with reduced amount of initiator for thiol−Michael dispersion polymerizations. Particles Made of Various Monomer Backbones. We investigated copolymerizations between PETMP and a series of diacrylates with various backbone structures to demonstrate the versatility of this step-growth polymerization method. As shown in Figure 10A, four diacrylates with various backbones were

Table 1. Glass Transition Temperatures and Size Distributions of the Particles Prepared from Stoichiometric Polymerization of PETMP and Various Diacrylatesa entry

diacrylate

Tgb (°C)

Tg half-width (±°C)

diameterc (μm)

CV (%)

1 2 3 4

HDDA TEGDA NPDA TCDDA

−36 −27 −17 8

2 3 2 3

3.6 7.4 7.1 7.7

53 57 59 29

a

Polymerization conditions: both the concentrations of thiol and acrylate groups were 0.2 mol/L in methanol (3 wt % PETMP, 2.8 wt % HDDA, 3.8 wt % TEGDA, 2.6 wt % NPDA, or 3.8 wt % TCDDA with respect to methanol), with approximately 20 wt % PVP and 5 wt % TEA used (both with respect to monomers). bThe glass transition temperatures were determined by differential scanning calorimetry. c The average diameter and coefficient of variance were determined from SEM images.

expected from the presence of the flexible ethylene glycol backbone in TEGDA. Interestingly, the half-widths of these polymers are all within 3 °C. Such sharp thermomechanical transitions are consistent with the uniformity of the stepgrowth polymer networks. A huge library of multifunctional acrylates has been developed largely for the applications of a variety of radical-mediated photopolymerization techniques. Numerous acrylic monomers include not only ones with varied rigidities but also ones containing functional groups for desired properties such as hydroxyl, fluoride, carboxylic acid, ammonium, and urethane. All these acrylic monomers are candidates for preparing microparticles with preferred physiochemical properties. The commercial resources also offer a selection of multithiol monomers for exploring structure− property relationships in the synthesis and ultimate behavior of microparticles. Besides the selection of various acrylic monomers, recently many novel multithiol compounds have been developed, for example, silane-containing thiols, which have been utilized in thiol−ene/thiol−Michael polymers with improved stability and mechanical properties.72 We expect these types of particles with robust tenability on their physical properties will find use in applications such as fillers for polymeric composites. Though the size distributions for these particles are relatively broad, it was not attempted to optimize the polymerization/microparticle formation conditions for each monomer system. To achieve monodispersity for these monomer mixtures, such factors as the amount of initiator, monomer loading, and polarity of solvent would need to be adjusted.

Figure 10. (A) Reaction scheme and (B) SEM images for microparticles prepared from PETMP and various diacrylates: (1) 1,6-hexanediol diacrylate (HDDA), (2) tetraethylene glycol diacrylate (TEGDA), (3) neopentyl glycol diacrylate (NPDA), and (4) tricyclodecane dimethanol diacrylate (TCDDA). Polymerization conditions: both the concentrations of thiol and acrylate groups were 0.2 mol/L in methanol (3 wt % PETMP, 2.8 wt % HDDA, 3.8 wt % TEGDA, 2.6 wt % NPDA, or 3.8 wt % TCDDA with respect to methanol), with approximately 20 wt % PVP and 5 wt % TEA used (both with respect to monomers).

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CONCLUSIONS A systematic investigation on thiol−Michael addition dispersion polymerizations was carried out. Cross-linked polymer microparticles were successfully prepared by thiol−Michael addition reactions between multifunctional thiols and acrylates. Methanol was mainly used as the reaction media with the presence of polyvinylpyrrolidone as a stabilizer. The diameters of the spherical microparticles were shown to be positively correlated with monomer loadings as well as the reaction media. Photoinitiation of the thiol−Michael addition dispersion polymerization was demonstrated by utilizing 2-(2nitrophenyl)propyloxycarbonyl protected amines in place of direct addition of amine catalysts. Particles were shown to be prepared from pentaerythritol tetra(3-mercaptopropionate) and various diacrylates with different backbones, as a

chosen, namely 1,6-hexanediol diacrylate (HDDA), tetraethylene glycol diacrylate (TEGDA), neopentyl glycol diacrylate (NPDA), and tricyclodecane dimethanol diacrylate (TCDDA). Particles were successfully prepared from those monomers under similar reaction conditions as those employed for the PETMP−TMPTA model system, as represented by SEM images shown in Figure 10B. The glass transition temperatures (Tg) of these particles as well as their sizes and size distributions are listed in Table 1. Among the aliphatic acrylates, the backbone rigidity increases from hexane to neopentane to tricyclodecane, and correspondingly the Tg rises from −36 to −17 to 8 °C for particles prepared with HDDA, NPDA, and TCDDA, respectively. The PETMP−TEGDA particles are characterized by a Tg as low as −27 °C, which is H


Article

Macromolecules

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demonstration of the adaptability of this polymerization process. Considering the vast adaptability of this dispersion polymerization protocol and the vast selection of monomer combinations that are possible, we believe that this work provides a tool for materials chemists and engineers to form monodispersity/narrow dispersity polymeric colloids with tunable, desired functionality, and behavior.

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AUTHOR INFORMATION

Corresponding Author

*E-mail [email protected] (C.N.B.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The work is supported by National Science Foundation (CHE 1214109 and DMR 1420736) and the U.S. Army Research Office (the MURI program, Award W911NF-13-1-0383). We thank Dr. Fuduo Ma and Prof. Ning Wu at the Colorado School of Mines for DLS measurements.

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Narrow Polydispersity Cross-Linked Microparticles

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