Hydrophobic Monomer Type and Hydrophilic Monomer Ionization

Jan 4, 2017 - The phase behavior and self-assembly structures of a series of amphiphilic diblock co-oligomers comprising an ionizable hydrophilic bloc...
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Hydrophobic Monomer Type and Hydrophilic Monomer Ionization Modulate the Lyotropic Phase Stability of Diblock Co-oligomer Amphiphiles Minh T. Lam, Paul A. FitzGerald, and Gregory G. Warr* School of Chemistry, The University of Sydney, Sydney NSW 2006, Australia S Supporting Information *

ABSTRACT: The phase behavior and self-assembly structures of a series of amphiphilic diblock co-oligomers comprising an ionizable hydrophilic block (5 to 10 units of acrylic acid) and a hydrophobic block (5 to 20 units of n-butyl acrylate, t-butyl acrylate, or ethyl acrylate), synthesized by RAFT polymerization, have been examined by polarizing optical microscopy and smallangle X-ray scattering (SAXS). Self-assembled structure and lyotropic phase stability in these systems is highly responsive to the degree of ionization of the acrylic acid hydrophilic block (i.e., pH), concentration, and nature of the hydrophobic block. Increasing headgroup ionization switched the amphiphiles from behaving like soluble to insoluble surfactants. Liquid isotropic (micellar), hexagonal, lamellar, and discrete cubic phases were found under different solution conditions. The surfactant packing parameter was adapted to understand the self-assembly structures in these diblock co-oligomers. The hydrophobic chain structure and length were shown to strongly affect the relative stabilities of these phases, allowing the self-assembled structure to be varied at will.

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INTRODUCTION Amphiphilic diblock copolymers are molecules composed of covalently linked hydrophobic and hydrophilic blocks that can self-assemble spontaneously in a melt or in solutions in which the solvent preferentially dissolves one block.1 Amphiphilic diblock copolymers are widely used in numerous applications (e.g., as stabilizers, emulsifiers, dispersants, compatibilizers, thickeners, foamers, and drug delivery agents).2,3 The self-assembly of various amphiphilic block copolymers has been investigated in a variety of solvents over many decades.4,5 Gao et al. observed reverse micellization of poly(styrene)-b-poly(butyl acrylate) in toluene.6 Tang et al. obtained spheres, vesicles, rodlike aggregates, and cauliflowerlike aggregates of self-assembling poly(ethylene oxide)-bpoly(p-nitrophenyl methacrylates) in different solvent mixtures such as dimethyl sulfoxide−methanol, −ethanol, or −water.7 He et al. found spherical wormlike micelles and bilayered vesicles from poly(1,2-butadiene)-b-poly(ethylene oxide) in an ionic liquid.8 Many studies of self-assembly have focused on the phase behavior of several amphiphilic diblock copolymers in aqueous solution (e.g., poly(styrene)-b-poly(acrylic acid),9,10 poly(dimethylsiloxane)-b-(poly(2-dimethylamino)ethyl acrylate),11 poly(n-butyl acrylate)-b-poly(acrylic acid),12,13 and poly(methylene)-b-poly(acrylic acid)).14 Poly(ethylene oxide) and poly(propylene oxide) block copolymers are among the most widely investigated and are known to form micelles and © 2017 American Chemical Society

lyotropic liquid crystals whose structure and stability depend on the ethylene oxide/propylene oxide ratio.15 It is difficult to systematically vary hydrophobic and hydrophilic block lengths to understand the design rules of the self-assembled structure in water. With the notable exception of poly(ethylene oxide) or other ethoxylated moieties, most hydrophilic blocks are charged (e.g., anionic acrylate or methacrylate or cationic, protonated aminoethyl acrylates). Conversely, hydrophobic blocks become water-insoluble at quite modest degrees of polymerization, leading to kinetically trapped nonequilibrium structures. Most of the amphiphilic diblock copolymers studied were composed of long-chain polymers or polymers with high average molecular weights. Amphiphilic diblock co-oligomers are similar to amphiphilic diblock copolymers but with shorter block chain lengths and lower average molecular weights. The precise definition of the term oligomer is somewhat inconsistent. The polymer handbook defines oligomers as polymers with molecular weights of up to 2000 g/mol,16 while an oligomer is defined by IUPAC as a compound composed of between 3 and 10 repeating monomer units.17 In the literature, an oligomer describes short-chain polymers with an average molecular weight of up to 5000 or 6000 g/mol.18−20 Received: August 23, 2016 Revised: November 3, 2016 Published: January 4, 2017 1013

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mesoporous silica thin films prepared on a solid electrode surface affected the permeability of the films (e.g., mass transport rates decreased when the nanopore structure changed from cubic to 3D hexagonal and then to a collapsed 2D hexagonal system).40 Therefore, determining the conditions for a specific morphology is necessary in order to form stabilized structures for targeted applications. In this work, the phase behavior and self-assembly structure of three different series of amphiphilic diblock co-oligomers [nbutyl acrylate-b-acrylic acid (BA5AA5), tert-butyl acrylate-bacrylic acid (tBAxAA5, x = 5, 7, or 10), and ethyl acrylate-bacrylic acid (EAyAA5, y = 5, 10, or 20)] were examined in aqueous solution by a combination of polarizing optical microscopy and small-angle X-ray scattering (SAXS). Each co-oligomer amphiphile was synthesized by reversible addition−fragmentation chain-transfer polymerization (RAFT), yielding copolymers with well-defined architectures, controlled molecular weights, and low polydispersity.41,42 Poly(acrylic acid) is a well-known weak polyelectrolyte that can selforganize into different structures depending on the degree of ionization and the pH of the surrounding solution.23 Because of this property of the acrylic acid hydrophilic block, the effect of ionization of the acrylic acid groups on the phase behavior of these amphiphilic diblock co-oligomers in water was studied to understand the conditions under which micelles and hexagonal, cubic, and lamellar mesophases are formed. The generic structure of the co-oligomers examined is shown in Figure 1, and the abbreviations used are summarized in Table 1.

Many conventional surfactants, such as sodium dodecyl sulfate, are excellent at reducing interfacial tension, but they have high critical micelle concentrations (cmcs), which requires large quantities of surfactant in commercial products to obtain the desired properties. In contrast, amphiphilic diblock copolymers with high molecular weights have small cmcs, but their self-assembly requires very long equilibration times.12,21,22 The self-assembly of amphiphilic diblock co-oligomers is an attractive option for avoiding both of these problems. Short amphiphilic diblock copolymers have better solubility of the hydrophobic block than long amphiphilic diblock copolymers and surface activity similar to that of conventional surfactants. Siaw et al. studied the phase behavior of two short amphiphilic diblock copolymers in aqueous solution, poly(ethylene glycol)-b-poly(styrene) (mPEG16-b-PS2,4,6) and poly(acrylic acid)-b-poly(styrene) (PAA14-b-PS16,33).18 Both systems formed micelles in water at a concentration of 6 mg/mL. The diameter of the micelles increased with an increase in the length of the hydrophobic block. Heinen et al. focused on the phase behavior of amphiphilic diblock co-oligomers n-butyl acrylate-b-2-hydroxyethyl acrylate (BA5-b-HEA5,6,7,8), styrene-bacrylic acid (S5,9,12-b-AA5), and n-butyl acrylate-b-acrylic acid (BA5,9,12-b-AA5) in aqueous solution.23 Systems of BA5-bHEA5,6,7,8 are nonionic amphiphilic diblock co-oligomers, whereas both S5,9,12-b-AA5 and BA5,9,12-b-AA5 are ionic. Spherical micelles were found in BA5-b-HEA5,6,7,8, while both spheres and lamellar structures were formed in BA5-b-HEA6,7,8. In ionic co-oligomer systems, S5,9,12-b-AA5 assembled only micelles, while BA5,9,12-b-AA5 aggregated into spherical and lamellar mesophases as the concentration of the co-oligomer was increased. The self-assembly of a short amphiphilic diblock copolymer, poly(butyl acrylate)-b-poly(acrylic acid) (BA15-bAA5, BA13-b-AA9), was considered by Lamprou et al.24 The morphology was spherical vesicles. According to this study, the self-assembly of such a short BA-b-AA amphiphilic diblock copolymer is dynamic in water, which is different from the kinetically frozen aggregation reported in the literature when the polymerization number of BA is greater than 20.12,13,21,22 Also, the degree of polymerization for the butyl acrylate block studied by Heinen is smaller than that for the co-oligomers in Lamprou’s work (e.g., BA5,9,12-b-AA5 versus BA15-b-AA5, BA13b-AA9). The assembled morphology is an essential factor in designing the desired properties of surfactants.25 Various morphologies are formed during the self-assembly of amphiphilic block copolymer in aqueous solution, including spheres, cylinders, cubic phases, bilayers, and so forth. For example, the morphology of the drug carrier is specifically addressed when considering applications of therapeutic agents. Many drug carriers have been designed using spherical micelles for delivering hydrophobic drugs,26−29 while others have used hexagonal micelles because of their higher stability in mammalian cells, wider range of cell growth media, and biodegradation.30−32 Cubosomes33−35 or vesicles36−38 have been employed as drug carriers containing both hydrophobic and hydrophilic pharmaceutical ingredients. In other applications, the self-assembly of cylindrical micelles of poly(ferrocenyldimethylsilane)-b-poly(2-vinylpyridine) block copolymer using as a templates for synthesis polyaniline nanofibers is potentially applied for nanodevice components.39 Mesoporous silica thin films have been used in sensors, membranes, chromatography, catalysis, and electrochemicalcell-based applications. The morphology of nanopores of

Figure 1. Representative structure of co-oligomers examined: m denotes the average degree of oligomerization of the hydrophobic monomer. In all cases, the average degree of oligomerization of the acrylic acid block was 5. (See the text.)

Table 1. Structures of R Groups of Hydrophobic Monomers Shown in Figure 1, Together with Degrees of Oligomerization (m) and Abbreviations Used for Each Cooligomer

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R-group structure

abbreviation

m

n-butyl t-butyl ethyl

BAmAA5 tBAmAA5 EAmAA5

5 5, 7 or 10 5, 10 or 20

MATERIALS AND METHODS

Acrylic acid (AA) monomer and 1,4-dioxane (both from SigmaAldrich) were purified by distillation under reduced pressure. Other monomers (Sigma-Aldrich), such as n-butyl acrylate (BA), tert-butyl acrylate (tBA), and ethyl acrylate (EA), were purified by passing through a basic alumina (Sigma-Aldrich) column to remove the inhibitor. Chain-transfer agent (CTA) 2-(((butylthio)carbonothioyl)thio) propanoic acid (C4RAFT, Dulux, Australia), 4,4′-azobis(4cyanovaleic acid) (V501, Fluka), deuterated dimethyl sulfoxide (DMSO-d6, Cambridge Isotope Laboratories), methanol (MeOH, Merck), and sodium hydroxide pellets (NaOH, Ajax Finechem) were 1014

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removed using a rotary evaporator under vacuum pressure to obtain the dry co-oligomer.

used as received. Water used in this work was purified with a MilliporeQ Plus water purification system (Milli-Q water, resistivity 18.2 MΩ cm). 1 H NMR spectra were recorded using a Bruker Ultra Shield Avance 300 MHz spectrometer at 25 °C. DMSO-d6 was used as the solvent for characterization. Solvent residual signals were utilized as internal references. All chemical shifts are reported in ppm (δ). The degree of polymerization of the first block, C4RAFT-AA5, was identified by electrospray ionization using a Finnigan LCQ spectrometer with XCalibur 2.0.7 control software for data processing. Crude C4RAFT-AA5 was diluted in MeOH, and 20 μL of the sample was injected with 0.3 mL/min MeOH flow into the ESI-MS in negative ion mode. The mass spectrum of the first block was recorded from 500 to 1000 m/z. The phase behavior of amphiphilic diblock co-oligomers in water was determined using a Leica DM2500P optical microscope equipped with a camera and crossed polarizers, including samples of solvent penetration experiments and equilibrated samples in water. Anisotropic liquid-crystal mesophases (hexagonal or lamellar) were identified on the basis of characteristic textures observed between crossed polarizers. In a solvent-penetration experiment, a small amount of co-oligomer was introduced onto a glass slide, covered with a coverslip, and then pressed to obtain a thin film. Afterwards, water was dropped at the edge of the coverslip and allowed to slowly penetrate into the co-oligomer, and subsequently formed mesophase structures were observed under the microscope. Small-angle X-ray scattering was performed using an Anton Paar SAXess with a sealed X-ray tube and generator with two cameras, one with point collimation and the other with line collimation. The X-ray scattering intensities of equilibrated diblock co-oligomers in water at various concentrations were collected and analyzed. The scattering intensities were recorded on image films, which were then read and reduced to intensity profiles by Optiquant and SAXSquant 2D software, respectively. The relative locations of the intensity peaks were used to identify liquid-crystal structures. Each amphiphilic diblock co-oligomer sample at a specific neutralized percentage was mixed with the required amount of MilliQ water to obtain the desired concentration. The co-oligomer and water were continuously mixed with a roller mixer at 40 rpm for 5 days at room temperature in order to reach equilibrium. Samples were typically found to equilibrate after 24 h, and selected monophasic samples subjected to heating/cooling cycles recovered their originally equilibrated structures over a similar time period. Multiphase samples in some cases took longer to recover, so 5 days was used as a conservative baseline. The co-oligomer sample was then characterized by SAXS and polarizing optical microscopy. Diblock co-oligomers were synthesized by reversible addition− fragmentation chain-transfer polymerization (RAFT). The first monomer AA (4.58 g, 0.0635 mol), chain-transfer agent C4RAFT (2.98 g, 0.0125 mol), and V501 initiator (0.175 g, 6.25 × 10−4 mol) were dissolved in 1,4-dioxane (22.98 g). The reaction mixture was purged with nitrogen for 15 min, and then stirred at 70 °C in an oil bath for 3 h. Afterwards, the reaction mixture was cooled to room temperature. The degree of polymerization of the C4RAFT-AA5 agent was characterized using 1H NMR and ESI-MS. The conversion was 94%, which was determined by 1H NMR. 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 0.85−0.92 (t, 3H, CH3−(CH2)3−S), 0.99−1.18 (d, 3H, −CH(CH3)COOH), 1.2−2.47 (m, CH3−CH2−(CH2)2−S−, CH3−CH2−CH2−CH2−S−C(S)−, AA5 backbone −CH2, AA5 backbone −CH, −CH(CH3)(COOH)), 4.6−4.8 (m, 1H, −C(S)−S− (CH(COOH) (CH2))5−CH(COOH) (CH3)), 12.2−12.5 (s, 5H, COOH). For the synthesis of the second block, appropriate amounts of the second monomer, dioxane, and initiator (0.0126 g, 4.5 × 10−5 mol) were added to a 2.2 g solution of the C4RAFT-AA5 agent (0.538 g, 9.0 × 10−4 mol). The reaction mixture was degassed by nitrogen for 15 min and subsequently stirred at 70 °C in an oil bath for 3 h. Reaction details of each type of second monomer and the conversion of the corresponding reaction are listed in Table 2. Diblock co-oligomers were characterized using 1H NMR. The dioxane solvent was then

Table 2. Reacted Quantity from the Synthesis of Each Type of Second Block and Conversion Yield co-oligomer

monomer

amount (g)

dioxane (g)

conversion (%)

BA5AA5 tBA5AA5 tBA7AA5 tBA10AA5 EA5AA5 EA10AA5 EA20AA5

n-BA t-BA t-BA t-BA EA EA EA

0.68 0.66 0.81 1.21 0.51 1.03 1.82

1.20 1.20 1.26 1.82 1.10 1.45 2.35

95 94 97 98 94 96 97

BA5AA5 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 0.8−0.95 (t, 18H, CH3−(CH2)3−S, −CH3 of BA5), 1.0−1.2 (d, 3H, −CH(CH3)COOH), 1.2−2.45 (m, CH3−CH2−(CH2)2−S−, CH3−CH2−CH2− CH2−S−C(S)−, AA5 backbone −CH2, AA5 backbone −CH, BA5 backbone −COO−CH2−, −CH(CH3) (COOH)), 3.75−3.85 (t, 2H, CH3−(CH2)2−CH2−S−C(S)−), 4.6−4.8 (m, 1H, −C(S)−S−(CH(COOH) (CH 2))5−CH(COOH) (CH3)), 12.2−12.4 (s, 5H, COOH). tBA5AA5 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 0.8−0.95 (t, 3H, CH3−(CH2)3−S), 1.0−1.2 (d, 3H, −CH(CH3)COOH), 1.2−2.45 (m, CH3−CH2−(CH2)2−S−, CH3−CH2−CH2−CH2−S−C(S)−, AA5 backbone −CH2, AA5 backbone −CH, tBA5 backbone −COO− C−(CH3)3, −CH(CH3) (COOH)), 4.6−4.8 (m, 1H, −C(S)−S− (CH(COOH) (CH2))5−CH(COOH) (CH3)), 12.2−12.4 (s, 5H, COOH). 1 H NMR spectra of tBA7AA5 and tBA10AA5 are similar to the 1H NMR spectra of tBA5AA5, but the numbers of protons were different from 1.2 to 2.45 ppm. EA5AA5 1H NMR (DMSO d6, 300 MHz) δ (ppm): 0.8−0.95 (t, 3H, CH3−(CH2)3−S), 1.0−1.2 (d, 3H, −CH(CH3)COOH), 1.2−1.4 (t, EA5 backbone −COO−CH2−CH3), 1.4−2.45 (m, CH3−CH2− (CH2)2−S−, CH3−CH2−CH2−CH2−S−C(S)−, AA5 backbone −CH 2 , AA 5 backbone −CH, EA 5 backbone −COO−CH 2 −, −CH(CH3)(COOH)), 3.75−3.85 (t, 2H, CH3−(CH2)2−CH2−S− C(S)−), 4.6−4.8 (m, 1H, −C(S)−S−(CH(COOH) (CH2))5− CH(COOH) (CH3)), 12.2−12.4 (s, 5H, COOH). 1 H NMR spectra of EA10AA5 and EA20AA5 are similar to the 1H NMR spectrum of EA5AA5, but the numbers of protons were different from 1.2 to 2.45 ppm. Each type of dry co-oligomer (0.005 g) diluted in 10 mL of Milli-Q water was titrated with 1.0 M NaOH using a Metrohm 744 pH meter to achieve the equivalence point of reaction between carboxyl groups in the corresponding co-oligomer and NaOH. The amount of NaOH at the equivalence point is equal to the required amount of NaOH to fully neutralize carboxyl groups in the co-oligomer. On the basis of the value of the equivalence point, we calculated the required amount of 1.0 M NaOH solution for 25, 50, 75, and 100% neutralization of each type of co-oligomer. After neutralization, each co-oligomer sample was dried to constant weight under vacuum.

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RESULTS AND DISCUSSION Characterization of Synthesized C4RAFT-AA5 and Amphiphilic Diblock Co-oligomers. The C4RAFT-AA5 homopolymer synthesized by the RAFT technique has a welldefined structure with the 1H NMR spectrum (Materials and Methods) of C4RAFT-AA5 showing an average of five protons from the AA groups observed between 12.2 and 12.4 ppm. Figure 2 shows the distribution of AA units for the first block (from ESI-MS) of about a mode of five AA units. Note that both the mass spectra and NMR results indicate a slightly longer average degree of polymerization for the AA block than in our previous study,23 consistent with the polymerization 1015

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Figure 2. ESI-MS of the C4RAFT-AA5 first block.

units, but two trends are seen: a higher degree of ionization is required before the Lα phase is first observed in the ternary phase diagram, and it remains stable up to 100% ionization. The lamellar phase remains stable phase at higher co-oligomer concentrations than the hexagonal phase, which forms only near 75% ionization. As the hydrophobic block length increases, Lα is stabilized relative to H1. The sequence of self-assembled structures and the trends with alkyl chain length are consistent with an interpretation based on the surfactant packing parameter model of Israelachvili et al.,44 v/aol, where v is the molecular volume of the hydrophobic tail, ao is the area of the headgroup at the polar/ nonpolar interface, and l is the chain length of the hydrophobic tail. The phase behavior of the fully ionized diblock cooligomers is very similar to that seen for micelle-forming ionic surfactants.45 In dilute solution at low electrolyte concentration (zero added salt), strong electrostatic repulsions between charged polar groups maximize ao for each hydrophobic block, whose volume, v, and length, l, are fixed by molecular geometry. This leads to compact, spherical micelles consistent with v/aol < 1/3. As the hydrophobic blocks are quite short and rotation is sterically hindered by the tert-butyl groups in these amphiphiles, they are expected to be better approximated by the fully-extended alkyl chain model used for conventional surfactants44 than an elastically deformed random flight conformation commonly used to describe longer blocks of copolymer amphiphiles.46 This micelle structure is consistent with the literature of a diblock copolymer micelle including a hydrophobic core and a corona of stretched polyelectrolyte chains47,48 (Micelle structure has been examined in detail by small-angle neutron scattering, which will be detailed in a forthcoming study of the L 1 phase). With increasing concentration, the ionic strength increases, with screening repulsions between charged headgroups, the reduction of ao,

being carried out for a longer time (3 h vs 2 h) and at higher temperature (70 °C vs 60 °C) in the present work. The structure of synthesized co-oligomers after adding the second block was analyzed by 1H NMR, yielding conversions of between 94 and 98% (Table 2). From the 1H NMR spectra, each type of co-oligomer contained five carboxylic groups from five AA units (Materials and Methods) and the correspondingly desired second block. Self-Assembly of tBAxAA5 (x = 5, 7, or 10). The isothermal phase diagrams of tBA5AA5, tBA7AA5, and tBA10AA5 in water are shown in Figure 3. These show the effect of ionization of the hydrophilic acrylic acid blocks as a pseudoternary system comprising a protonated co-oligomer (e.g., tBA5AA5) and its salt (e.g., tBA5AA5-Na+ including the ionizable RAFT agent end-group) in aqueous solution. No ordered structures are formed in mixtures of the acidic (hydrogen) form of tBA5AA5 and water. The mixtures included a swollen solid and water, which are denoted as SSW in the phase diagrams (see captions). The swollen solid was caused by water absorption by the hydrophilic acrylic acid block.43 In contrast, the fully deprotonated (100% ionized) acrylate species are much more soluble in water, and these form extended liquid isotropic (micellar) phases up to approximately 25 wt %. At higher concentrations, one or more lyotropic mesophases are present along the binary H2O−tBA5AA5−Na+ axis and at lower degrees of ionization. In tBA5AA5 at 25% ionization, a lamellar phase (Lα) is first detected in a range of co-oligomer concentration between 60 and 70 wt % and remains stable up to at least 50% ionization. At higher ionizations, the lamellar phase is transformed into a direct hexagonal phase (H1), which persists up to 100% ionization, tBA5AA5-Na+, and over a wide concentration range. The same sequence of lyotropic mesophases is observed as the hydrophobic block length is increased to 7 and then 10 tBA 1016

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decreasing water activity and changes in steric interactions between hydrophilic ethoxy groups.49 Further increasing concentration leads to a lamellar phase in tBA7AA5-Na+ and tBA10AA5-Na+ but not in tBA5AA5-Na+. This trend is again consistent with the increasing electrolyte/ decreasing water activity further reducing ao until v/aol > 1/2, where planar or bilayer structures become favored over spheres or cylinders. The absence of a lamellar phase in the fully ionized tBA5AA5-Na+ is a consequence of the short hydrophobic block, which never allows planar structures to be favored before the solubility limit is reached. This matches the trend seen in polyoxyethylene n-alkyl ether (CmEn) nonionic surfactants, where the Lα phase is also less stable as nonpolar, alkyl, chain length m is decreased at a fixed polar, ethoxy, chain length n.49 The effect of ionization of the acrylic acid groups on the phase behavior of tBAxAA5 in water is also consistent with packing parameter considerations. Both the L1 and H1 phases are stable only well above 50% ionization in their respective concentration ranges. Decreasing ionization is expected to decrease ao and therefore favor less curved aggregates. This is also seen in the behavior of the Lα phase, which is not only stable at much lower degrees of ionization than either L1 or H1 but which also becomes stable over a wider composition range as the ionization decreases. This reflects the increasing importance of steric rather than electrostatic interactions in stabilizing the self-assembly structure. The lower ionization stability limits of the H1 and L1 phases, a little below 75%, correspond to the transition of these cooligomer amphiphiles from soluble, micelle-forming surfactants to insoluble, bilayer-forming (or lipidlike) amphiphiles.50 In other words, the broad two-phase coexistence region of the diluted lamellar phase is a vesicle dispersion in excess water, which means that a micelle−vesicle transition can be triggered by a pH change anywhere along the L1 concentration range (0−25 wt % tBAxAA5-Na+). Further decreasing ionization leads to the precipitation of solid co-oligomer, usually as an opaque solid or gel with occluded water. The effect of the hydrophobic monomer structure on the self-assembly structure was examined by comparing isomeric monomers n-butyl and tert-butyl acrylate in tBA5AA5 and BA5 AA5 prepared from the same starting C 4RAFT-AA 5 oligomer. This is shown in Figure 4. In previous work, we compared butyl acrylate with styrene hydrophobic blocks in similar systems, but styrene’s hydrophobicity and high Tg led to phase diagrams dominated by solid phases.23 Both tBA5AA5 and BA5AA5 form micelles (L1) in dilute solution at high degrees of ionization and a hexagonal phase at higher co-oligomer concentrations. Both tBA5AA5 and BA5AA5 also form lamellar phases at higher co-oligomer concentrations and at lower degrees of ionization. However, the difference between tBA5AA5 and BA5AA5 is most pronounced when the lamellar phase of BA5AA5, not only forms at higher minimum degrees of ionization (25% ionization) than for tBA5AA5 but also remains stable even at 100% ionization. This is a straightforward consequence of tBA monomers being more compact than those of BA. Hence, the hydrophobic block can pack closer together in tBA than BA, leading to a smaller packing parameter at the same degree of ionization. This is consistent with the trends in the phase behavior and morphology of tBA5AA5, tBA7AA5, and tBA10AA5 (Figure 3), which increasingly favor the lamellar over the hexagonal phase at 100% ionization as the hydrophobic block length increases.

Figure 3. Ternary phase diagram of (a) tBA5AA5, (b) tBA7AA5, and (c) tBA10AA5 in water with experimental data. The boundaries were approximated to enclose the experimental data. L1, H1, Lα, SSW, and OS denote micelle, hexagonal, and lamellar phases, mixtures of swollen solid and water, and an opaque solid. Symbols refer to experimental data points (red ■, liquid isotropic (micellar) phase (L1); green ▲, hexagonal phase (H1); blue ⧫, lamellar phase (Lα); purple ●, two or three phases; and ×, an unidentified phase). The dotted lines in (a) show water-dilution paths of co-oligomers at 25, 50 and 75% ionization of the carboxylate groups.

and the increase in v/aol. When this value exceeds 1/3, the favored aggregate morphology becomes cylinders, corresponding to the hexagonal phase. This transition is also seen upon increasing concentration of nonionic surfactant solutions due to 1017

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Figure 4. Ternary phase diagram of BA5AA5 in water with experimental data. The boundaries were approximated to enclose experimental data. L1, H1, Lα, SSW, and OS denote micelle, hexagonal, and lamellar phases, mixtures of swollen solid and water, and an opaque solid. Symbols refer to experimental data points (red ■, liquid isotropic (micellar) phase (L1); green ▲, hexagonal phase (H1); blue ⧫, lamellar phase (Lα); purple ●, two or three phases; and ×, unidentified phase).

The phase behavior of the BA5AA5−water system shown in Figure 4, and particularly the effect of ionization of the acrylic acid groups, is in good agreement with our previous work.23 Here, however, we detect a hexagonal phase near 100% ionization of BA5AA5-Na+. This is attributed to the longer reaction time used to prepare the AA block, yielding a longer average block than in the previous system. This highlights the sensitivity of the self-assembly structure to small changes in the average degree of polymerization of the acrylic acid hydrophilic block. A small change is sufficient to alter the relative stability of the hexagonal and lamellar mesophases, paralleling trends seen in the phase behavior of conventional CnEm nonionic surfactants with decreasing ethoxy chain length.49 Self-Assembly of EAyAA5 (y = 5, 10, or 20). An advantage of block copolymer or co-oligomer amphiphiles afforded by the large library of monomers with varying degrees of hydrophobicity, rather than being constrained to hydro- or fluoro-carbon chains of traditional surfactants, has been exploited extensively in poly(ethylene oxide)-poly(propylene oxide) copolymers, for example,51 in which longer hydrophobic blocks lead to larger structures without sacrificing solubility. In this spirit, we have examined the phase behavior of co-oligomer amphiphiles built from ethyl acrylate hydrophobic monomers EA5AA5, EA10AA5, and EA20AA5 in water. Partial phase diagrams are shown in Figure 5. In EA5AA5 (Figure 5a), the L1 phase is stable up to almost 50 wt % in water over a much wider range of ionization than with either the BA or tBA hydrophobic tails. This is taken to be a straightforward consequence of the higher water solubility of EA monomers such that EA5 is much less hydrophobic than either BA5 or tBA5. The lamellar phase of EA5AA5 is similarly stable at low degrees of ionization, and like tBA5AA5-Na+, this is attributed to the compactness of the ethyl moiety. At high degrees of ionization, the now-familiar hexagonal phase is observed between the L1 and lamellar phases, which remains stable up to 100% ionization.

Figure 5. Ternary phase diagram of (a) EA5AA5, (b) EA10AA5, and (c) EA20AA5 in water with experimental data. The boundaries were approximated to enclose experimental data. L1, I1, H1, Lα, SSW, and OS denote micelles, discrete cubic, hexagonal, and lamellar phases, mixtures of swollen solid and water, and an opaque solid. Dashed lines are extending phase boundaries. Symbols refer to experimental data points (red ■, liquid isotropic (micellar) phase (L1); purple right triangle, discrete (I1) cubic phase; green ▲, hexagonal phase; blue ⧫, lamellar phase (Lα); purple ●, two or three phases, and ×, unidentified phase).

Increasing EA length to 10 or 20 monomers collapses the L1 phase toward the 100% ionization axis as the block’s overall hydrophobicity becomes comparable to that of blocks of BA5 1018

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surfactant packing parameter, although in a modified form for block co-oligomers, as discussed below. Whereas our previous study23 showed that the stability of the L1 phase and solubility limit depended strongly on n-BA or the styrene block length, this article shows that this effect is attenuated in tBA and even more so in EA co-oligomers. This is consistent with their much smaller exposed hydrophobic side groups, enabling easy decoupling of hydrophobicity from the self-assembled structure. We expect that the surfactant packing parameter, v/aolc, can easily be adapted to understand self-assembly structures in these diblock co-oligomers: In conventional surfactants, the hydrophobic (alkyl) chain length is a primary control parameter for self-assembled structures because it determines both v and lc (using Tanford’s formulas56). However, high chain melting or Krafft temperatures of saturated alkyl chains longer than C16 limit the range of aggregate sizes that can be assembled. The weakly hydrophobic propylene oxide monomers used to make Pluronic copolymers are one of few widely utilized counterexamples. These amphiphilic co-oligomers contain hydrophobic blocks with fully extended lengths, lc, ranging from 23 Å for 5mers (comparable to a C16 alkyl hydrophobe) up to 60 Å for EA20. The ethyl-, t-butyl, and n-butyl side chains independently alter the hydrophobic packing volume, v, and tune the hydrophobicity. Thus, at the same degree of ionization, more highly curved structures are favored by the more compact ethyland t-butyl- monomers, at the same block length and degree of ionization. Two factors complicate the adaptation of the packing parameter to diblock co-oligomers, both related to the meaning of lc. The first is well known in block copolymer assembly: As the block length increases, the probability of adopting an alltrans chain of length lc becomes vanishingly small so the hydrophobic core needs to be instead considered an unperturbed chain in its melt. The range of hydrophobic chain lengths examined in these systems represents a transition from C4RAFT+5-mer, with an effective alkyl chain length approximately equivalent to a C16 alkyl tail, and hence most like a small surfactant, up to EA20, which would correspond to about C46. The probability of an all-trans conformer of EA20 is negligible, so the chain length in the packing parameter, v/aolc, as applied to conventional surfactants must be recast in terms of the random coil dimension of the hydrophobic block. Thus, although v increases linearly with the degree of polymerization of the hydrophobic block, the hydrophobic core radius of the aggregate should increase more slowly with increasing tail length. The packing parameter should therefore increase markedly, favoring less-curved aggregates. The second consideration relates to the packing of hydrophobes inside the core of the aggregates formed. Even within the paradigm of the surfactant packing parameter, the all-trans conformation lc is an upper bound on the core radius and therefore defines the most highly curved structure that can form. The interpenetration of tails in the core favors more planar structures. In our previous study,23 fitting the SAXS patterns of lamellar phases of BA5-, BA9-, and S5-AA5 cooligomers yielded hydrophobic block thicknesses much smaller than two fully extended hydrophobic chains. This suggested that the hydrophobic blocks were highly intercalated and/or the chains were coiled. Here we have taken a slightly different approach to analyzing the lamellar phase SAXS patterns. We partition the cooligomers into hydrophobic and hydrophilic volume fractions

isomers. For EA10AA5, the lamellar phase retains its stability from low ionizations, also like the BA5AA5 systems (Figure 4), up to 100% ionization. Here the hexagonal-phase region is larger, and for the first time, a cubic phase is observed between L1 and H1. Indexing of SAXS patterns (√3:√4:√8:√11, see Supporting Information) indicates that this is a discrete (I1) cubic phase comprising micelles on a face-centered-cubic lattice.52−54 The emergence of an I1 cubic phase with increasing hydrophobic block length is at first sight counterintuitive, as this should favor less-curved (higher packing parameter) structures. However, the I1 phase forms from the L1 region by an ordering transition that does not involve a change in aggregate shape. It is known in ionic surfactant systems that short hydrophobic chains give rise to high cmcs and high ionic strengths that suppress the repulsions needed for I1 phase formation.55 In the EA20AA5 co-oligomer system (Figure 5c), the stability ranges of the hexagonal and lamellar phases are markedly smaller than in EA10AA5. When the chain length of EA is increased to 20 repeating units, the solubility of the co-oligomer in water decreases so that the concentrations at which hexagonal and lamellar phases formed are lowered. At 75% ionization and concentrations of between 35 and 40 wt %, EA20AA5 forms a discrete (I1) cubic phase.52 The phase is optically isotropic, but the Bragg peaks in the SAXS patterns could not be unambiguously indexed to any known cubic phases. This may be due to two (or more) cubic phases of different symmetry arising at nearby compositions (and refractive indices) in this region. None of the lyotropic phases I1, H1, or Lα could be isolated in binary mixtures of the fully ionized co-oligomer and H2O. Rather, optical micrographs and SAXS patterns are consistent with two coexisting phases (Supporting Information). From 40 to 60 wt %, several broad and overlapping peaks occurred in the SAXS that we attribute to coexisting I1 and H1 phases, and from 65 to 70 wt %, SAXS patterns are consistent with coexisting hexagonal and lamellar phases. This is consistent with I1, H1, and Lα phases remaining stable up to 100% ionization of EA20AA5-Na+, but each existing alone over a very narrow concentration range. This is indicated in Figure 5c by the dashed phase boundaries extending to the 100% ionization axis. Like the tBAnAA5 and BAnAA5 systems,23 ethyl acrylate blocks also act as hydrophobes that enable amphiphilic cooligomer self-assembly when the acrylic acid moieties are at least partially ionized. Also like BA-based co-oligomers, increasing the degree of ionization of the acrylate block increases the solubility of longer EA chains. At low ionization, the co-oligomers behave like sparingly soluble surfactants and exhibit a broad two-phase coexistence region (vesicle dispersion) between a lamellar phase and a very dilute aqueous solution. However, increasing the ionization allows micelles to form in the L1 phase, leading to the formation of discrete cubic and hexagonal mesophases. The only departure from this occurs for very short EA5 blocks, which are themselves soluble in water even at low AA5 ionization. Controlling Self-Assembly. The control of self-assembly may be broken into two components: hydrophobicity and structure. Hydrophobicity is determined by the side chains (i.e., ethyl vs t-butyl vs n-butyl), while structure is determined by a combination of tail length, hydrophobic volume, and headgroup ionization, all of which modify self-assembly through the 1019

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Table 3. Hydrophobic Repeat Spacing (D*), Volume Fraction (ϕ) and Block Thicknesses (thydrophobe) for Co-oligomer Lamellar Phasesa BA5AA5 tBA5AA5

tBA7AA5

tBA10AA5

EA5AA5

EA10AA5

EA20AA5

% ionization

wt % co-oligomer

D* (Å)

ϕhydrophobe

thydrophobe (Å)

lc (Å)

75 50 75 50 25 100 75 50 100 75 50 100 75 50 25 100 75 50 25 100 75 50 75 50

65 65 65 65 65 65 65 65 65 65 65 70 70 70 70 70 70 70 70 65 65 65 65 65

61.6 65.1 59.8 63.4 65.1 62.0 70.1 73.8 73.8 76.5 88.4 51.5 51.8 55.2 56.0 64.7 69.3 71.4 73.0 65.1 71.4 75.3 92.6 95.4

0.46 0.47 0.45 0.45 0.46 0.46 0.48 0.48 0.50 0.50 0.51 0.42 0.43 0.44 0.45 0.54 0.55 0.56 0.57 0.51 0.51 0.53 0.57 0.58

28.0 30.8 26.6 28.7 30.0 28.7 33.3 35.7 36.8 38.6 45.4 21.5 22.2 24.2 25.1 35.0 38.1 39.9 41.5 33.1 36.8 39.6 52.6 54.9

23.0 23.0

28.1

35.7

23.0

35.7

35.7

61.0

thydrophobe is calculated from the scattering dilution law (see the text), and lc is calculated from Tanford’s formula.56 ϕhydrophobe, D*, and lc denote the hydrophobic volume fraction, the repeat spacing of the primary diffraction peak, and the fully extended length of a single chain, respectively.

a

chemistry of the hydrophobic and hydrophilic blocks. These undergo spontaneous self-assembly in aqueous solution into micelles and subsequent organization into lyotropic phases, which depends on the block length and type. For example, here both the monomer hydrophobicity (ethyl-, t-butyl-, and nbutyl-acrylate) and block length (n = 5−10) have been varied, allowing the bilayer thickness in lamellar phases to be designed synthetically and then further modulated by changes in the ionization of the hydrophilic acrylic acid group. As with conventional surfactants, the stability of different lyotropic phases is determined by packing constraints.49 Somewhat surprisingly, in co-oligomers even the shortest hydrophobic chains were examined when packed in a coiled and intercalated arrangement, similar to long polymer chains. The range of monomers available for free-radical polymerization promises a vast new library of block-co-oligomer amphiphiles incorporating controllable functionality and responsiveness to environmental variables including pH, electrolyte or specific ions, or temperature,58 both alone and in combination for sensor or triggered-release applications.59

using their known densities and then use the dilution law for diffraction, ϕhydrophobe = thydrophobe/D*, where ϕ denotes the volume fraction and D* is the repeat spacing of the primary diffraction peak, to determine the hydrophobic block thickness. In every system examined, we find again that the hydrophobic blocks are much thinner than expected, with the overall hydrophobic block thickness close to the fully extended length of a single chain from 5-mers to 20-mers. The results are summarized in Table 3. We interpret this to be a consequence of the side chains of the hydrophobic moieties, which do not readily pack into the same orderly arrangement as alkyl chains: they must coil back onto themselves and/or intercalate in order not to leave voids in the hydrophobic core. That is, even the shortest hydrophobic blocks do not pack like the alkyl tails of conventional surfactants but interpenetrate like a polymer melt. Our results show that BA5 forms slightly thicker bilayers than does tBA5 under the same conditions and that EA5 bilayers are thinner still. Thicker bilayers are likely to be a consequence of greater steric hindrance to rotation around the backbone, restricting the ability of the chain to adopt more compact conformations. For a given system, the hydrophobic core thickness decreases slightly as the degree of ionization increases. This is consistent with an increase in repulsion between neighboring AA chains within a single bilayer increasing the area per chain; in order to conserve volume, the hydrophobic core thins.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.6b03133. SAXS patterns and optical microscopy images of discrete cubic phase of EA10AA5 100% ionization, discrete cubic phase of EA20AA5 75% ionization, and the coexisting hexagonal and lamellar phases of EA20AA5 100% ionization (PDF)

CONCLUSIONS

Controlled radical polymerization techniques such as RAFT, used here and previously by us,23,57 enable the preparation of novel amphiphilic co-oligomers comparable with conventional surfactant and with exquisite control over the lengths and 1020

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Paul A. FitzGerald: 0000-0002-8897-3821 Gregory G. Warr: 0000-0002-6893-1253 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was funded by the Australian Research Council Discovery and infrastructure grants. We thank Dr. Algi Serelis from Dulux Australia for providing the RAFT agent used in this study and Prof. Sébastien Perrier for valuable discussions.

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