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Chapter 8
Programmed Self-Assembly of Amphiphilic Random Copolymers in Water via Controlled Radical Polymerization Takaya Terashima* Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan *E-mail:
[email protected].
Self-assembly of amphiphilic polymers in water is a key technology to construct nanostructured materials with controlled architectures. Herein, we introduce programmed self-assembly systems of amphiphilic random copolymers into size-controlled micelles and nanoaggregates in water. Importantly, the primary structure of the copolymers, controlled by living radical polymerization, serves as encoded information to determine the size, structure, properties, and functions of the micelles and nanoaggregates. This chapter summarizes the recent advances of random copolymer self-assembly on 1) design and synthesis, 2) self-folding, self-assembly, and thermoresponsive properties, 3) compartmentalized nanomaterials, and 4) functions.
Introduction Self-assembly of amphiphilic molecules and polymers in water is a powerful strategy to build nanomaterials with well-defined three-dimensional architecture. Various amphiphilic copolymers bearing hydrophobic segments have been developed as self-assembly precursors: e.g., amphiphilic block, random, alternating, and graft copolymers (1–12). The size and architecture of self-assembly objects depend on the primary structure of the polymers such as chain length, composition, monomer sequence distribution, and branching structure. Block copolymers are the mainstream of the precursors; they typically
© 2018 American Chemical Society Matyjaszewski et al.; Reversible Deactivation Radical Polymerization: Materials and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 2018.
provide globular, rod-like, and multicompartment micelles, vesicles, and nanoaggregates (1–3, 11, 12). In contrast to such general trends, we recently developed precision self-folding and self-assembly systems of amphiphilic “random” copolymers bearing hydrophilic poly(ethylene glycol) and hydrophobic and/or functional pendants in water (Figure 1) (5, 13–31). The key is to design well-controlled random copolymers; they are effectively synthesized by metal-catalyzed living radical polymerization (32, 33). The random copolymers bearing hydrophobic pendants induce self-folding and/or self-assembly in water via the association of the hydrophobic pendants to form uniform micelles with hydrophobic cores that are covered by hydrophilic PEG chains (15–17). The size (~10 nm) is much smaller than that of micelles normally obtained with amphiphilic block copolymers. Importantly, by tuning the primary structure such as chain length, composition, and pendant structure, the random copolymers afford precision and on-target control of size, aggregation number, and thermoresponsive properties. Thus, the primary structure determined by living radical polymerization serves as encoded information for programmed self-assembly into micelles and nanoobjects with controlled size, nanodomains, and three-dimensional structures.
Figure 1. Self-assembly systems of amphiphilic random copolymers with precision primary structure in water: From design and self-folding/self-assembly to nanostructured materials and functions.
In this chapter, we review the recent advances on the self-assembly of amphiphilic random copolymers, especially focusing on 1) design and synthesis, 2) self-folding, self-assembly, and thermoresponsive properties, 3) compartmentalized nanomaterials, and 4) functions. Common amphiphilic random copolymers now innovate in self-assembly technologies: Synthetic linear polymers with precision primary structure can be transformed via self-folding and 144 Matyjaszewski et al.; Reversible Deactivation Radical Polymerization: Materials and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 2018.
self-assembly into on-target globular materials with controlled three-dimensional structures like proteins and enzymes.
Design and Synthesis Amphiphilic random copolymers with hydrophilic poly(ethylene glycol) pendants and hydrophobic alkyl or functional (hydrogen-bonding, fluorous) pendants were designed as precursors to induce self-folding or self-assembly into micelles in water or organic media. The primary structure of the copolymers including molecular weight (chain length) and composition (molar or weight fraction of hydrophobic segments) was controlled by living radical polymerization for desired self-folding and self-assembly properties.
Figure 2. Synthesis of PEGMA/RMA amphiphilic random copolymers via ruthenium-catalyzed living radical copolymerization of hydrophilic PEGMA and hydrophobic or functional RMA.
Well-controlled random copolymers were synthesized by rutheniumcatalyzed living radical copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA, Mn = 475) and hydrophobic or functional methacrylates (RMA) (Figure 2) (15–18, 21–31). To find primary structure suitable for self-folding in water, RMA content and degree of polymerization (DP) were varied as follows: RMA = 20 – 50 mol%; DP = 50 – 200. Typically, PEGMA and various hydrophobic methacrylates (e.g., dodecyl methacrylate: DMA) were efficiently and smoothly copolymerized in high yield (>80%) with a ruthenium catalyst [Ru(Ind)Cl(PPh3)2/n-Bu3N] and a chloride initiator (ethyl 2-chloro-2-phenylacetate) in toluene at 80 °C to give well-controlled random copolymers with narrow molecular weight distribution [Mw/Mn = 1.1 – 1.4, determined by SEC with PMMA standard calibration] (15–17, 26). Importantly, random, statistical distribution of the hydrophilic and hydrophobic monomers in copolymers was supported by the simultaneous consumption of the monomers at the same speed, independent of monomer feed ratio and alkyl pendant species. 145 Matyjaszewski et al.; Reversible Deactivation Radical Polymerization: Materials and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 2018.
Random copolymerization of PEGMA and hydrogen-bonding monomers with urea or amide pendants (BPUMA, BTAMA, see Figure 2) requires the use of polar solvents such as ethanol and 1,4-dioxane (18–21). For example, PEGMA and urea-bearing BPUMA were simultaneously consumed at the same speed in ethanol to give PEGMA/BPUMA random copolymers (21). In contrast, BPUMA was faster consumed than PEGMA in the mixed solvent of toluene and ethanol, providing PEGMA/BPUMA gradient copolymers; the sequence distribution was changed from BPUMA-rich segment at α-end to PEGMA-rich segment at ω-end. Increased reactivity of the urea-bearing monomer would be attributed to hydrogen-bonding interaction or self-assembly of the monomer in less polar solvents. The copolymerization of PEGMA and fluorous methacrylates (e.g., 1H,1H,2H,2H-perfluorooctyl methacrylate: 13FOMA) in toluene effectively provided corresponding random copolymers (22–25). Thus, various random copolymers were successfully obtained from ruthenium-mediated polymerization systems coupled with a chloride initiator and suitable solvents.
Self-Folding, Self-Assembly, and Thermoresponsive Properties Controlled Self-Folding Amphiphilic random copolymers efficiently induce self-folding into unimer micelles in water and/or organic media (Figure 3). The folding properties were evaluated by size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS), dynamic light scattering (DLS), and small angle X-ray scattering (SAXS).
Figure 3. Controlled self-folding of (a) PEGMA/DMA, (b) PEGMA/BPUMA, and (c) PEGMA/13FOMA random copolymers in aqueous and organic, and fluorinated media. 146 Matyjaszewski et al.; Reversible Deactivation Radical Polymerization: Materials and Applications ACS Symposium Series; American Chemical Society: Washington, DC, 2018.
Owing to multiple hydrophilic PEG pendants, all the PEGMA-based random copolymers were homogeneously soluble in water. For example, copolymers comprising hydrophobic alkyl pendants shorter than dodecyl groups (-C12H25) immediately dissolved in water just by mixing them with water at room temperature without any specific procedures. In contrast, to prepare homogeneous aqueous solutions of copolymers with crystalline octadecyl pendants (-C18H37), heating the solution at 50 °C, followed by sonication, was required (15–17, 26). Typically, a PEGMA/DMA random copolymer with 40 mol% DMA and 200 DP intramolecularly self-folded in water via the self-assembly of the hydrophobic dodecyl pendants to form quite small unimer micelles with hydrophobic cores (~10 nm) (15, 17). The absolute weight-average molecular weight in water by MALLS (Mw,H2O) was almost identical to that in DMF (Mw,H2O), while the hydrodynamic radius (Rh,H2O) in water by DLS was smaller than that in DMF. This result fully supports self-folding into compact unimer micelles in water. The core-shell structure was also supported by SAXS (17). Folding mode of random copolymers can be effectively controlled by selecting functional pendants. The copolymers with hydrophobic pendants (hydrophobic monomer content:
