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Nonionic Amphiphilic Linear Dendritic Block Copolymers. SolventInduced Self-Assembly and Morphology Tuning Xin Liu† and Ivan Gitsov*,†,‡ †

Department of Chemistry, State University of New York-ESF, Syracuse 13210, United States The Michael M. Szwarc Polymer Research Institute, Syracuse 13210, United States

‡

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S Supporting Information *

ABSTRACT: In this article, we report the solution self-assembly of a series of amphiphilic linear−dendritic block copolymers (LDBCs), which are composed of hydrophilic dendritic poly(ether-ester), PEE, blocks based on 2,2-bis(hydroxymethyl)propionic acid and hydrophobic linear poly(styrene), PSt, blocks. The investigated LDBCs have narrow dispersity with three PEE generations (1−3) and a broad range of PSt molecular masses and are produced by dendron-initiated atom transfer radical polymerization of styrene followed by deprotection of the peripheral dendron hydroxyl groups. The solution self-assembly of the copolymers is performed by slowly adding water to the polymer solution in tetrahydrofuran (THF) as the common solvent for both blocks of the copolymers. The morphologies of the supramolecular assemblies are preserved either by diluting their dispersion by excess of water or by THF evaporation. It is found that the micellar morphology (sphere, wormlike, and/or vesicle) depends on the hydrophilic block fraction (FPEE) and dendron generation. The self-assembly morphology transition from vesicle to wormlike micelle or sphere is achieved by switching the common solvent from THF to dimethylformamide. Interestingly, LG2-PSt 18k forms a bicontinuous phase, while LG3-PSt 68k forms onion-like aggregates with acetone as the common solvent. Palladium complexation within the dendron block leads to formation of cubosomes and other structures with morphology of higher order.

1. INTRODUCTION Amphiphilic block copolymers are giant analogues of low molecular mass surfactants and as such are drawing increased attention for the preparation of nanosized materials with desirable exploitation characteristics. In block-selective solutions, they could organize into a broad range of structures including spheres, cylinders, lamellae, vesicles,1−4 toroids,5,6 and other more complex morphologies.7,8 These supramolecular particles are not only more stable compared to those derived from common surfactants but are also more chemically tunable thus providing more functionality and application versatility. By replacing one block of the traditional linear−linear copolymer with a dendritic unit, the resulting linear−dendritic block copolymers (LDBCs) provide an attractive alternative to traditional self-assembling materials.9,10 The amphiphilic dendritic poly(benzyl ether)-block-poly(ethylene glycol) or PBE−PEG LDBCs, prepared by the “coupling” strategy were forming unimolecular or multi© XXXX American Chemical Society

molecular micelles in methanol and water mixtures depending on the polymer concentration and dendron generation.11 Several important studies followed this initial publication. Dendritic poly(propylene imine)-block-poly(styrene) or PPI− PSt LDBCs were synthesized by divergent synthesis on amineterminated PSt by van Hest et al.12 It was found that these amphiphilic LDBCs aggregate into vesicles, rods, and spheres as PPI generation increased in high agreement with Israelachvili’s molecular packing parameter theory.13 Stupp’s group reported the synthesis of dendron-rod-coil LDBCs, which could self-organize into nanoribbons in dichloromethane (DCM) via π−π stacking and hydrogen bonding.14 More recently, LDBCs bearing a PEG-terminated Percec-type dendron and linear PSt were found to form colloidal Received: May 17, 2019 Revised: June 27, 2019

A

DOI: 10.1021/acs.macromol.9b01023 Macromolecules XXXX, XXX, XXX−XXX

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Figure 1. Chemical structures of three generation LDBCs: LG1-PSt, LG2-PSt, and LG3-PSt. fluoroacetic acid (99%), TFA, were bought from Sigma-Aldrich and used without further purification. 2.2. Methods. 2.2.1. Synthesis of the LDBCs. The LDBCs were prepared by dendron-initiated ATRP followed by a deprotection step to remove the acetonide protecting group on the PEE, Scheme S1.23 An example of the dendritic initiator preparation and polymerization procedures is provided in the Supporting Information. 2.2.2. Self-Assembly of LDBCs in Water by a Cosolvent Method. The copolymer (10 mg) was dissolved in 1 mL THF as the common solvent for both PEE and PSt blocks. The solution was stirred at room temperature for 1 h and filtered through a 0.45 μm polytetrafluoroethylene membrane to remove any insoluble residue. Water as selective solvent for the PEE block was injected to the polymer solution at 1 mL/h rate using a syringe pump with the needle inserted into the solution (Figure S18). The solution became milky as the water content (Vw) reached a critical value, indicating formation of aggregates. When Vw reached 50%, the aggregates were vitrified by taking 50 μL of the THF/water copolymer solution and injected into 1 mL of pure water. If a mixture of different morphologies (spheres and worms or lamellae and vesicles) was expected, THF in the polymer solution was slowly evaporated at ambient temperature for 24 h. More stable aggregates were prepared by diluting polymer solutions into water 50 times. The change in the morphology with a different common solvent was achieved with the same protocol as above. 2.2.3. Preparation of LDBCs Palladium Complexes. The polymer and PdCl2(CH3CN)2 were dissolved separately in THF and stirred for 30 min. PdCl2(CH3CN)2 was used at the same molar quantity as the theoretical binding sites. Then, the two solutions were combined and stirred for 15 min to obtain the LDBC Pd complex with desired initial polymer concentration before addition of water. It was noticed that the yellowness of the PdCl2(CH3CN)2 solution dramatically decreased upon mixing with the polymer solution. The self-assembled particles were prepared using the same procedure described above. 2.3. Characterization of the Self-Assembled Morphologies. Aggregate morphology was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). A drop of the aggregate suspension was deposited on carbon coated copper grid for 5 min and blotted by lint-free paper to remove extra solution. The grid was air dried for 1 h at ambient temperature and further vacuum-dried for 24 h before being analyzed by TEM with a JEOL JEM-2100F microscope at an accelerating voltage of 200 kV. The samples were not stained unless specified. The image was

cubosomes with tunable surface groups for enzyme immobilization.15,16 Our group has recently synthesized a family of amphiphilic Janus dendrimers based on poly(ether-ester), PEE, and poly(benzyl ether), PBE, dendrons. These dendrimers form vesicles or thermosensitive micelles in water.17 Taking advantage of the functionalities, created by “click” chemistry, the dendrimers have promising application potential in catalysis by bonding palladium to every branching site.17,18 However, the synthesis of these Janus dendrimers is demanding and time consuming. The control of the hydrophilic to hydrophobic ratio is limited to variations in the dendron generation unless dendron of other type is used, which in turn would involve more synthetic work.19 On the other hand, LDBCs are synthetically easier to prepare and still possess most of the attractive properties of Janus dendrimers.20,21 Recently, Lebedeva et al. theoretically predicted that dendronization of the corona will lead to relatively stable LDBC micelles with a high degree of functionality at the surface.22 Inspired by the previous experimental and theoretical studies and our early success of incorporating the PEE dendrons into self-assembling macromolecules, we evaluate in this study the solution behavior of a new family of amphiphilic LDBCs. The unique structure of PEE is not only expected to facilitate the generation of various micellar morphologies but should also be able to facilitate the formation of palladium complexes.17,18 These LDBCs have a water-soluble PEE head and poly(styrene) (PSt) tail and are produced by dendron-initiated atom transfer radical polymerization (ATRP).23 The solution self-assembly of these LDBCs and the micellar morphology tuning will be presented and discussed. Their structures are shown in Figure 1.

2. EXPERIMENTAL SECTION 2.1. Materials. Tetrahydrofuran (HPLC grade), THF; dimethylformamide (Reagent grade), DMF, and acetone (HPLC-UV grade) were purchased from Pharmco-Aaper and used as received. Bis(acetonitrile)dichloropalladium (99%), PdCl2(CH3CN)2, and triB

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Figure 2. Digital photographs (a−d) and TEM images (e−h) of LG1-PSt 3.5k, in THF/H2O solutions at different water volume contents (Vw). (a/ e) Nonuniform solid spheres: Vw = 40%; (b/f) planar lamellae with shrunken spheres at the edge: Vw = 44%; (c/g) giant vesicles and their optical phase contrast image: Vw = 48%; (d/h) stable vesicles: Vw = 50% and vitrified. recorded by Gatan OneView CCD camera and analyzed by GMS 3 software. High-angle annular dark-field scanning TEM and electron dispersive X-ray spectroscopy (EDXS) were also performed with JEM-2100F. For SEM sample preparation, a drop of the particle suspension was cast on a piece of clean glass, air-dried, and then sputter-coated with a thin layer of Au/Pd. The coated sample was analyzed on a JEOL JSMIT100 microscope.

(i.e., the PEE dendron weight fraction, FPEE). It is determined by 1H NMR using the methyl groups on the 2,2-bishydroxymethyl propionic acid unit in PEE and the aromatic protons of PSt.23 LG1-PSt 3.5k with FPEE = 27.8% is initially used in the investigation of solution self-assembly to validate the method. The polymer solution stays clear until Vw reaches 40%. As the water content increases to 44%, small flaky objects are spotted in the opaque bluish solution. When Vw approaches 48%, the small flakes disappear, and the entire solution becomes less turbid with suspension of giant vesicles. We assume that these giant vesicles are formed by enclosure of planar lamellae. Upon stirring, the large vesicles break into smaller vesicles as Vw reaches 50%. The smaller vesicles are identified as unilamellar objects with ∼2.1 μm diameter by TEM studies. The polymer aggregate morphology evolution from spheres to lamellae then to large vesicles and finally to smaller vesicles at different water content is presented in Figure 2. A real time morphology transition is also observed in other polymers.27 The second test is performed with LG1-PSt 4.9k with FPEE 18.3%. Its solution turns milky at a lower water content (34%) than LG1-PSt 3.5k due to the higher hydrophobicity. As Vw reaches 50%, giant vesicles are found in the presence of the large amount of insoluble solids, suggesting that at this concentration, the small first generation PEE dendron is not able to disperse and solubilize efficiently the relatively large PSt domain. LG1-PSt 8.9k (FPEE = 10%) precipitates in 1:1 THF/H2O solution without forming any defined colloidal structures. This is why the solution self-assembly of LG1-PSt with higher molecular weight is not further investigated. The morphologies of aggregates created by solution selfassembly of the second generation LDBCs with PSt of various lengths are displayed in Figure 3. LG2-PSt 5k with FPEE = 44.5% (second generation LDBC with the lowest overall molecular mass) forms solid spherical micelles. The solution stays clear throughout the entire assembly process without any detectable increase of turbidity, indicating that the particle sizes are very small. The average radius of the PSt domain is measured as 6.1 nm from TEM images. A very interesting “lenticular” morphology with resemblance to a convex lens is observed with LG2-PSt 7.2k (FPEE = 30.4%) in the vitrified polymer solution when 50 vol % of water is reached, Figure 3b. The “lenticular” objects could be interpreted as folded planar lamellae or “half-enclosed vesicles”. Similar phenomenon is also observed in the aggregates generated by LG2-PSt 8.5k

3. RESULTS AND DISCUSSION 3.1. Synthesis of LDBCs. The synthesis of LDBCs is performed through dendron-initiated ATRP of styrene in bulk at 95 °C. With the benefit of controlled polymerization, the length of the PSt tail is tunable by varying polymerization time and catalyst concentration. The unreacted dendron initiator is easily removed by passing the polymer solution through basic alumina (Figure S1). The use of acetonide protecting groups on the periphery of the PEE dendron is required during the polymerization stage to prevent potential ester bond cleavage under basic conditions and elevated temperature. They are removed by simply treating the LDBCs in DCM solution with TFA at room temperature (see Figures S2 and S3). The overlaid SEC traces of LDBCs used in this study are presented in Figure S4. The 1H NMR spectra of all copolymers are included in the Supporting Information file, Figures S5−S17. 3.2. Self-Assembly of LDBCs by a Cosolvent Method. The solution self-assembly of these LDBCs is investigated using the “cosolvents” or “phase inversion” method.24 The main reason to adopt this method rather than solvent-free methods such as film hydration or injection is to overcome the high glass transition temperature of PSt. THF as a good solvent for both PEE and PSt blocks is used to dissolve the LDBCs initially instead of previously used dioxane25 because the PEE dendron block has very low solubility in it. The copolymer initial concentration is fixed at 10 mg/mL in this section. Water, a nonsolvent for PSt and good solvent for PEE, is slowly added to the polymer solution to generate nanoprecipitation, Figure S18.26 As the added water reaches a certain amount, namely, critical water concentration, the solution turns cloudy, indicating aggregate formation. When the water content reaches 50% (Vw = 50%), relatively stable aggregates are formed by vitrification of the PSt domain by 50fold dilution of the solution. The morphology of these aggregates is analyzed by microscopy. The final morphologies could depend strongly on the hydrophilic to hydrophobic ratio C

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Figure 3. TEM images of LG2-PSt LDBCs aggregates with different FPEE (a) LG2-PSt 5k, spherical micelles, stained by 2% uranyl acetate; (b) LG2-PSt 7.2k, vesicles and folded lamellae (arrow pointed), vitrified from THF/H2O 1:1 solution; (c) LG2-PSt 7.2k, THF evaporated from the THF/H2O solution; (d) LG2-PSt 10k, vesicles, vitrified from THF/H2O 1:1 solution; (e) LG2-PSt 14k, vesicles, vitrified from THF/H2O 1:1 solution; (f) LG2-PSt 18k is not fully dispersible in 1:1 THF/H2O. The vesicles are prepared by vitrification of the upper solution layer.

Figure 4. TEM images of LG3-PSt LDBCs aggregates with different FPEE (a) LG3-PSt 15k, wormlike micelles in the presence of small amount of toroids, vitrified at Vw = 50%; (b) LG3-PSt 20k, wormlike micelles in the presence of small number of vesicles, vitrified at Vw = 50%; (c) LG3-PSt 25k, vesicles, THF evaporated from the THF/H2O 1:1 solution mixture; (d) LG3-PSt 30k, vesicles, vitrified at Vw = 50%; (e) LG3-PSt 40k, vesicles, vitrified at Vw = 50%; (f) LG3-PSt 68k, vesicles, vitrified at Vw = 50%.

slowly to obtain stable aggregates. Upon complete THF removal, vesicles with an average diameter of 135 nm are generated, Figure 4c. As FPEE drops further, pure vesicles are observed in the vitrified polymer solution when Vw reaches 50%, implying faster morphology transition, Figure 4d−f. The parameters of these LDBCs and the type of their selfassemblies in the mixed THF/H2O medium are summarized in Table 1. As previously demonstrated,28−30 the morphology of block copolymer aggregates is strongly affected by the conformation of the hydrophobic tail. Here, we also use the degree of stretching (S) to quantify the state of the PSt tail: stretched, relaxed, or compressed. S is defined as the ratio of radius of the micellar core to the end to end distance of the PSt chain in the unperturbed state (R0).

(FPEE = 26.9%), see Figure S19. By slowly evaporating THF in the solvent mixture (THF/H 2 O 1:1), pure vesicular morphologies with diameter from 190 to 600 nm are observed, Figure 3c. Few smaller vesicles with diameter around 100 nm are also present (Figure S20). As FPEE drops to 16.7%, a pure vesicular phase is observed in the vitrified polymer solution from the THF/H2O 1:1 mixture. When FPEE decreases further to 13%, LG2-PSt 18k is no longer fully dispersible in the THF/ H2O 1:1 mixture. The polymer suspension has a light milky upper layer with visible particles settled on the bottom. Vitrification of upper solution produces vesicles with 185−570 nm diameter, Figure 3f. Not surprisingly, inversed micelles with sponge-like structure are occasionally also observed with this copolymer due to the low hydrophilic/hydrophobic ratio, Figure S21. The morphologies of aggregates formed by the third generation LDBCs are displayed in Figure 4. As the FPEE decreases, the morphologies transition from wormlike micelles to a mixture of wormlike micelles and vesicles, to pure vesicles. LG3-PSt 15k and 20k form mainly wormlike micelles with a high aspect ratio (>500), Figure 4a,b. Noticeably, a small amount of toroids is also found in LG3-PSt 15k micelles (Figures 4a and S22). LG3-PSt 25k vitrified at Vw = 50% contains an intricate mixture of worms, flattened worms, lamellae, and vesicles (Figure S23), indicating that the morphology is still not settled. This is why THF is evaporated

S = R /R 0 R 0 = 0.067M 0.5

where M (g/mol) is the average molecular mass, and 0.067 is an independent constant.27 S is related to several factors including the repulsion of corona, PSt−solvent interaction, and the PSt chain length. For the PSt−poly(acrylic acid) copolymers, investigated by Eisenberg,28 S is between 1.7 and 1.5 in THF/H2O. Our LG1-PSt and LG2-PSt LDBCs have similar S values, Table 1. They indicate that the PSt block is extended due to the high interaction with THF. As the PSt chain grows longer, S decreases slightly to compensate for the D

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Macromolecules Table 1. Self-Assembly Parameters of LDBCs Using THF as the Common Solvent sample LG1-PSt LG2-PSt LG2-PSt LG2-PSt LG2-PSt LG2-PSt LG2-PSt LG3-PSt LG3-PSt LG3-PSt LG3-PSt LG3-PSt LG3-PSt

3.5k 5.0k 7.5k 8.5k 10k 14k 18k 15k 20k 25k 30k 40k 68k

Mn (kDa)a

Đb(%)

FPEE

morphology

Rc(nm)

Sd

3.5 5.1 7.5 8.5 10.1 14.2 18.2 15.1 20.1 25.0 30.2 39.9 67.8

1.08 1.06 1.06 1.06 1.07 1.08 1.09 1.08 1.09 1.10 1.12 1.16 1.16

27.80 44.50 30.40 26.90 23.00 16.70 13.00 34.20 25.70 20.10 16.70 12.30 7.60

Vesicle Sphere Vesicle Vesicle Vesicle Vesicle vesicle wormlike wormlike vesicle vesicle vesicle vesicle

6.5 6.1 7.4 8.2 9.0 10.0 11.9 8.50 10.05 10.50 11.23 12.10 16.10

1.89 1.65 1.49 1.51 1.50 1.49 1.40 1.20 1.18 1.08 1.04 0.95 0.95

a

Determined by SEC using PSt standards. bMolecular mass distribution (Mw/Mn) determined by SEC. cRaverage radius of PSt chain (micellar core) measured from TEM images. For vesicles, R is the half of the wall thickness measured from intact vesicles. dSPSt degree of stretching defined as the ratio of experimental radius to the end-to-end distance of PSt in the unperturbed state.28

higher entropic penalty. However, the degrees of stretching in the micelles generated by LG3-PSt LDBCs are surprisingly low ranging from 1.2 to 0.95 in the same solvents. It is known that the strong repulsion of the corona leads to volume shrinkage in the micellar core.27 Thus, it is reasonable to assume that the high hydrophilicity and expanded topology of the thirdgeneration dendron are causing strong repulsions in the micellar corona and therefore lead to shrinkage of the PSt domain. If one compares LG1-PSt 3.5k, LG2-PSt 8.5k, and LG3-PSt 20k, three generations of LDBCs with the similar hydrophilic/hydrophobic ratio (similar FPEE), clearly, there is an increase of the micellar curvature (giant vesicle, small vesicle, and wormlike) due to the stronger repulsion of higher generation PEE. It should be mentioned that this generation effect of the micellar corona is prominent when the PSt tail is relatively short. As the PSt tails grows longer, they dominate the self-assembly process, and the generation effect is diminished. 3.3. Mechanism of Vesicle Formation. The mechanism of vesicle formation potentially influences encapsulation efficacy, which is important in future applications such as drug delivery. As discussed above, the giant vesicles of LG1PSt are formed by lamellae enclosure. To further elucidate the mechanism in the second and third generation LDBCs, the morphologies, vitrified at a lower water content, are analyzed by TEM. Two mechanisms of vesicle formation are often discussed: (1) the copolymer unimers initially form spherical micelles and then grow into lamellae with a tendency for enclosure leading to vesicles; (2) the copolymers form large clusters followed by diffusion of solvent into the core causing the formation of “semivesicles” which evolve into full vesicles as rearrangements occur within the hydrophilic and hydrophobic segments.31 Mechanism 1 is widely observed in many studies on polymersomes, formed by linear−linear block copolymers.32−35 For our second generation LDBCs, the lamellae are observed in the solutions when Vw is low, and then vesicles are generated from the wrapped bilayer and detached from the large lamellae (Figures 5a,b; 6 and S24). Slightly differing from the first- and second-generation LDBCs, the vesicles derived from third-generation LDBCs go through a wormlike intermediate. LG3-PSt 25k provides a good example for this morphology transition. First, interlinked spherical micelles are observed at Vw = 10% when the solution

Figure 5. TEM images of intermediates before the vesicles form in THF/H2O. (a) LG2-PSt 14k: Vw = 10%; (b) LG2-PSt 14k: Vw = 30%; (c) LG3-PSt 25k: Vw = 10%; (d) LG3-PSt 25k: Vw = 40%; (e) LG3-PSt 68k: Vw = 10%; and (f) LG3-PSt 68k: Vw = 20%.

turns slightly opaque. Then, mixtures of worms, flattened worms, lamellae, and partially folded lamellae and vesicles are formed at Vw = 40 and 50% (Figures 5c,d and S23). It is apparent that initially the self-assembly yields spheres, and then, the spheres interlink to form wormlike micelles, which become flat as more water is added. The flattened micelles (lamellae) wrap up, and vesicles are generated. The radius of PSt domains in these self-assemblies decreases in the following order: Rsphere (12.2 nm) ≥ Rworm (12.1 nm) > Rvesicle (10.5 nm). Similar morphology transition is also observed in LG3-PSt 30k and 40k (Figure 6 and S25). E

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Figure 6. Summary of morphology transition of LDBCs in THF with different water contents (Vw). Representative TEM images of the captured intermediate morphologies (S: sphere; W: wormlike; L: lamella; and V: vesicle). (A) Second-generation LDBCs; (B) Third-generation LDBCs.

Figure 7. TEM images of LDBC self-assemblies using different common solvents: (a) LG2-PSt 18k in THF/H2O; (b) LG2-PSt 18k in DMF/H2O; (c) LG3-PSt 40k in THF/H2O; and (d) LG3-PSt 40k in DMF/H2O.

3.4. Morphology Tuning by Changing the Common Solvent. The morphologies of block copolymers could be manipulated by changing several factors such as the common solvent, initial polymer concentration, and presence of ions.3,29,30,38 In this section, we investigate the effect of the common solvent on LG2-PSt 18k and LG3-PSt 40k, two different generation LDBCs with similar FPEE. The final morphology depends on the balance of corona repulsion and PSt−solvent interaction. DMF could be considered as a better solvent for the PEE dendron than THF due to the higher ability for hydrogen bonding and increased polarity. It is also a worse solvent for PSt. Both factors would presumably cause a decrease in the aggregation number thus leading to a morphology of lower order. As expected, in DMF/H2O 1:1, LG2-PSt 18k forms networks composed of wormlike micelles with Y junctions, while LG3-PSt 40k forms uniform spheres (Figures 7 and S26). The average diameter of worms from LG2-PSt 18k is 13.95 nm, by 4.5 nm smaller than the thickness

Interestingly, LG3-PSt 68k with FPEE = 7.6% follows vesicle formation mechanism 2. Figure 5e,f shows a mixture of solid spheres and “semivesicles” generated during the self-assembly. Noticeably, only 9% of water causes LG3-PSt 68k THF solution to turn very milky. This means that the rearrangement of the two blocks could not be completed in such a short period. The fast copolymer aggregation is possibly due to the long highly hydrophobic PSt tail. In other words, the segregation of PEE and PSt lags behind the copolymer aggregation; thus spheres with poorly organized two blocks are initially formed. As more selective solvent diffuses into the spheres, the partially solvated polymers reorganize to form the stable bilayer. This mechanism has been elaborated by simulation studies, reported by Uneyama and Schmid.36,37 The long PSt tail is the main factor contributing to this vesicle formation mechanism. The intermediate morphologies at different Vw are collectively shown in Figure 6. F

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LDBC organizes into a mixture of lamellae and wormlike micelles (vitrified from acetone/H2O 1:1). At 2 mg/mL, this copolymer forms a mixture of branched wormlike micelles and spheres (see Figure S29). More interestingly, in acetone/H2O at the same concentration (2 mg/mL) LG3-PSt 68k, the largest LDBC with the lowest FPEE synthesized in this research forms onion-like particles with 0.35−1.8 μm diameter, Figures 9 and S30. The thickness of each “onion” layer is ∼21 nm. Because this copolymer composition is highly asymmetric (PEE and PSt are vastly different in size), the nanosized “onions” are not analogous to previously reported block copolymer particles with lamellar structures.40 Considering the open-end organization of the “onions” (see arrows in Figure 9) and the coexistence of wormlike micelles with similar diameters to the size of the “onion” layers (Figure S30b), these unusual aggregates could be formed from wrapped wormlike micelles. The interaction of PEE to the selective solvent might lead to repulsion of the worm micelles, while the strong hydrophobic effect of the long PSt chains and van der Waals forces probably favor agglomeration. Thus, the formation of the “onions” could result from the delicate balance of these two opposite tendencies. Although using acetone as common solvent for LDBCs with low FPEE could lead to more interesting and complex structures, the mixture of different phases is always detected possibly due to the fast precipitation. 3.5. Morphology Tuning by Complexing LDBC to Palladium. Chemical modification of triazole rings created by “click” chemistry is an intriguing method to self-assembled nanostructures prepared by block copolymers. For example, ionization of the triazole ring at the junction of the two blocks in the block copolymers could lead to enhanced microphase separation.41 Triazole rings are also known to be able to complex to transition metals providing a convenient approach to prepare metal organic hybrid materials.42 In this study, we are exploring the possibility of modifying the morphology of the colloidal linear−dendritic particles by palladium (Pd) complexation to the triazole rings located at the branching points of the PEE dendrons (Scheme 1). A PEE dendron complexed with Pd is less water soluble thus leading to increase in the hydrophobic/hydrophilic ratio of the copolymer which will potentially affect the self-assembly morphology. Two-third generation LDBCs, LG3-PSt 15k and 68k, are chosen to demonstrate the proof of principle concept. Remarkably, morphology transition to higher orders is observed. The PD complex of LG3-PSt 15k forms a pure vesicle phase (Figure 10) compared to the wormlike micelles generated by the original LDBC (Figure 4a) at the same initial polymer concentration and water content. To better understand the origin of the morphology transition, the surface areas (a0) of the PEE head and its Pd complex are calculated to elucidate the geometry of the block copolymer. Experimentally, a0 is measured as29

of the vesicle wall prepared from the same polymer. It could be assumed that the reduced hydrophobic domain is the main cause of morphology transition because the PSt chain is more compact in DMF. However, the average diameter of the spheres formed by LG3-PSt 40k is 24.6 nmvery close to the wall thickness (∼24.2 nm) of the corresponding vesicles prepared in THF. It is obvious that the PSt domains are compressed in both supramolecular structures. Thus, it is the stronger repulsion of the third-generation PEE corona (more voluminous in DMF) that causes the morphology change. The self-assembly of the above two polymers using acetone as common solvent is also investigated. It is noted that the very low water content (Vw = 1%) causes the aggregation of LG2PSt 18k in the acetone solution at 10 mg/mL and irregularshaped large particles are observed. Thus, a lower initial polymer concentration (2 mg/mL) and slower water addition rate (0.5 mL/h) are used to extend the relaxation time and potentially prevent irregular aggregations caused by fast precipitation. Inverted micelles are observed in the aggregates vitrified from acetone/H2O 1:1 solution with coexistence of vesicles and flat lamellae, Figures 8a, and S27. Because these bicontinuous structures are not spatially ordered as indicated by fast Fourier Transfer (FFT) of the image and some of the pores are not interconnected, they should be designated as the “sponge phase” or referred to as “spongisomes”.39 In order to create a pure sponge phase by this polymer, the initial polymer concentration is increased to 5 mg/mL. Unfortunately, a mixture of vesicle, lamella, and sponge phases is still produced. Notably, the size of the inverted micelles grows to ∼10 μm and the internal pore sizes increase, as well. The SEM study demonstrates that the inverted micelles have a tissue paper “pom-pom”-like shape (Figures 8b and S28). The TEM study shows that the porous bicontinuous internal network is wrapped with a bilayer of ∼16 nm thickness, Figure 8d. In the self-assembly of LG3-PSt 40k using acetone as common solvent with an initial concentration of 5 mg/mL, the

a0 =

iVStNPSt fR

where i is a geometrical parameter (1 for vesicle, 2 for wormlike, and 3 for spheres); VSt is the volume of the styrene monomer; NPSt is the degree of polymerization of the PSt tail; f is the fraction of PSt in the micelle core which reaches 1 at high water content; R is the radius of the micelle core measured as in Table 1. According to the calculation, the

Figure 8. Inverse micelle or “spongisome” of LG2-PSt 18k vitrified from 1:1 acetone/H2O (a) TEM image: [LDBC] = 2 mg/mL, inset: FFT of the marked area; (b) SEM image of “spongisome”, [LDBC] = 5 mg/mL; (c) SEM image of deformed “spongisome” dried from the same sonicated sample in (b) to reveal the internal structure; (d) TEM image of “spongisome”, the same sample as in (b). G

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Figure 9. Nanosize onion-like structures prepared from LG3-PSt 68k vitrified from 1:1 acetone/H2O in the presence of tangled wormlike micelles.

Scheme 1. Schematic Demonstration of Complexing Palladium to the LDBC

Figure 10. (a) TEM images of vesicles formed by the Pd complex with LG3-PSt 15k. (b) Pd clusters with ∼2 nm diameter are observed on the vesicle membrane; inset: a vesicle used to measure the membrane thickness.

surface area of PEE (∼3.9 nm2) decreased to 2.2 nm2 once it complexed with Pd, possibly due to the limited freedom of rotation at the branching unit and strong association of ethylene glycol moieties to Pd.43 Shrinkage of the area occupied by the head group increases the packing parameter p calculated as p = v/a0l resulting in the observed morphology transition. In agreement with the above observation, the LG3-PSt 68k Pd complex forms higher-ordered morphology as the bicontinuous phase (Figures 11a and S31) at lower initial polymer concentration (4.5 mg/mL) compared to the original LDBC (vesicle forming at 10 mg/mL). Free cubosomes (Figure 11b) and vesicle-conjugated cubosomes (Figure S32a) together with a small amount of less organized bicontinuous particles (Figure S32b) are observed. Closer analysis of the TEM images of the cubosomes at higher magnification and different viewing angles reveals that the geometrical relationship of the water channels is consistent with body-centered cubic symmetry (Im3̅m, primitive, Schwartz P surface), and the unit cell parameter “a” is measured as 58 nm. Figure 11c displays a TEM image of a part of a cubosome oriented to the electron beam along [111] direction. By tilting the sample by

Figure 11. TEM images of self-assembled morphology of the LG3PSt 68k Pd complex at 4.5 mg/mL initial concentration: (a) an overview of the cubosomes; (b) Im3̅m cubosome; (c,d) TEM image of parts of a cubosome viewed along [111] and [110] direction, respectively. The light areas are corresponding to the water channels; insets are the FFT of the images. (e) TEM images of a part of the cubosome viewed along [100] direction; the inset is the FFT of the image; the two unit cells of the two noninteracting water channels are marked as blue and red squares; (f) schematic illustration of the bicontinuous network.

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4. CONCLUSIONS In summary, we studied the solution behavior of series of amphiphilic linear−dendritic PEE-co-PSt block copolymers formed by dendron-initiated ATRP followed by deprotection of the PEE dendrons. The controlled length of the PSt block formed regulates the hydrophilic to hydrophobic ratio or FPEE of the copolymer. The solution self-assembly of these LDBCs is accomplished by slowly adding water to the THF solution of the copolymers and vitrifying the morphology of the aggregates by diluting with excess water. Various morphologies including spheres, worms, vesicles, and inverse micelles are obtained depending on the hydrophilic to hydrophobic ratio of the LDBCs. In the first- and second-generation LDBCs, the strong interaction of PSt with THF and compact conformation of the PEE dendrons cause a PSt tail stretch in the self-assemblies. However, the PSt tails in the third-generation LDBCs are relaxed due to the strong repulsion of the third-generation PEE dendrons. The self-organized morphologies of these LDBCs are tunable by varying the common solvent. When DMF is used instead of THF, lower order morphologies are observed. It is worth mentioning that LG2-PSt 18k forms a sponge phase, while LG3-PSt 68k produces multilayered onion-like structures when acetone is used as the common solvent. More interestingly, the supramolecular morphology shifts to higher orders (cubic bicontinuous and inverse hexagonal) when the LDBCs are complexed with Pd as an outcome of the shrinkage in the surface area of the PEE head. The Pd cubosome particles with highly ordered pores have potential applications in catalysis.

30°, the particle is oriented to the electron beam along the [110] direction revealing {002} and {11̅0} reflections (Figure 11d) which is an important feature of Im3̅m cubic phase. Figure 11e presents a TEM image of a part of the cubosome viewing along [100] direction, which is also consistent with Im3̅m symmetry.44,45 Thus, other bicontinuous phases with Pn3̅m, Ia3̅d, and Fd3̅m symmetries could be ruled out. A schematic illustration of the bicontinuous network is presented in Figure 11f showing eight repeating units using the Schwartz P surface as the model. The complete tilt series of the cubosome used to determine the symmetry is provided in Supporting Information, Movie S1 (the cubosome was tilted from −30° to +30° by 1.5° increments). Im3̅m cubosomes could be considered as a phase between sponge and Pn3̅m (double diamond, Schwartz D surface) phase.46,47 To test the stability of the Pd complexes in the cubosome, we performed EDXS analysis of a cubosome aged four months (Figure S33). Notably, Pd is still present in the supramolecular lattice, which suggests that these Pd-loaded cubosomes could potentially find applications in catalysis. More quantitative research will be performed in the future. Searching for other higher ordered phases, the initial concentration of the LG3-PSt 68k Pd complexes is further increased to 6 mg/mL, which results in irregular-shaped particles of micrometer scale (Figures 12a,b

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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.macromol.9b01023. Materials and instruments, synthesis of LDBCs, and additional SEM and TEM images (PDF) TEM tilting series of the cubosome used to determine the symmetry (MP4)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone: 1-315-470-6851. Fax: 1315-4706856.

Figure 12. TEM images of self-assembled morphology prepared from the LG3-PSt 68k Pd complex at 6 mg/mL initial concentration. (a) Micrometer scale particles, inset: SEM image with 1 μm bar; (b) enlarged image of marked area in (a); (c,d) TEM image at high magnification showing hexagonally packed palladium-loaded PEE domains in the PSt matrix: the darker areas are corresponding to the domain formed by Pd-complexed PEE dendrons (high electron density); the lighter areas are PSt domains (lower electron density).

ORCID

Ivan Gitsov: 0000-0001-7433-8571 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Partial funding of this study was provided by the National Science Foundation (BIO-DBI 1531757). We thank Benjamin Zink from Department of Environmental Biology, SUNY-ESF for his assistance with the TEM and SEM imaging, and The Michael M. Szwarc Memorial Fund for a summer fellowship to X.L.

and S34). Inside these particles, palladium-complexed PEE dendrons form cylinders with ∼6 nm diameter and pack hexagonally in the PSt matrix (Figure 12c,d). This phase is analogous to the inverse hexagonal (HII) phase found in lipid systems48 and block copolymers with relatively shorter hydrophobic domains;46,47 however, it lacks water channels. It is possible that the hydrophobic domain favors aggregation at high polymer contents due to the strong van der Waal forces between the long PSt tails, which compresses the area of water channels and finally cause their disappearance.

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