Synthesis and Self-Assembly of Amphiphilic Hybrid Nano Building

Aug 21, 2014 - Nano building blocks (NBBs) decorated with well-defined polymer .... Synthetic Advances, Self-Assembly and Applications in Biomedicine ...
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Synthesis and Self-Assembly of Amphiphilic Hybrid Nano Building Blocks via Self-Collapse of Polymer Single Chains Weikun Li, Chung-Hao Kuo, Istvan Kanyo, Srinivas Thanneeru, and Jie He* Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States S Supporting Information *

ABSTRACT: Nano building blocks (NBBs) decorated with well-defined polymer tethers have emerged as a promising type of building blocks for constructing hierarchical materials through programmable self-assembly. We present a general and facile strategy for preparing hybrid NBBs composed of silica-like heads decorated with well-defined polymer tethers by the self-collapse of polymer single chains. Using amphiphilic block copolymers (BCPs) of poly(ethylene oxide)-block-[poly(methyl methacrylate)-co-poly(3-(trimethoxysilyl)propyl methacrylate)] (PEO-bP(MMA-co-TMSPMA)), the intramolecular hydrolysis and polycondensation of silane moieties led to the formation of hybrid NBBs with silica-like heads and PEO tethers. The formation of hybrid NBBs was carefully characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, transmission electron microscopy, and static/dynamic light scattering. In a mixed solvent of THF/water, amphiphilic NBBs could assemble into spherical micelles, vesicles, and large compound micelles, depending on the size of silica heads and the initial concentrations. The intramolecular cross-linking of P(MMA-co-TMSPMA) blocks significantly altered the assembly behavior of linear BCPs. The rigid hydrophobic heads of NBBs could not be stretched/compressed, and the selfassembly of NBBs behaved surfactant-like. Furthermore, we observed that the mismatched dimensions of NBBs and linear BCPs would give rise to the formation of unprecedented phase-separated bilayer vesicles when coassembling two amphiphiles. Our study of NBBs may bridge the study of nanoparticles and polymeric building blocks and offer new opportunities to synthesize hybrid NBBs with controlled functionalities for use in novel functional materials and devices.

1. INTRODUCTION Nano building blocks (NBBs) composed of nanoparticle (NP) cores with well-defined polymer tethers have been recognized as a new type of “colloidal molecules” for the bottom-up construction of functional materials and devices.1−7 One emerging approach to program the self-assembly of NBBs in a desired manner is to engineer surface patterns or decorations that can direct the self-assembly to predesigned structures.8−15 Glotzer’s group has pioneered the design of NBBs decorated with polymer tethers and the self-assembly of such NBBs in a selective solvent.16,17 The theoretical simulations from her group suggested that the self-assembly of these NBBs would yield untraditional hierarchical structures and phase behaviors under the directional instruction of polymer tethers.18 Despite great efforts being made in the field, the design and synthesis of NBBs with well-defined tethers, particularly with specific NPs core geometries and topologies, are still in their early stages with very few successful examples. The current synthetic methods of polymer tethered NBBs, including selective surface modification,19,20 kinetically controlled synthesis,21 postfunctionalization on cagelike inorganic compounds,11,22 and encapsulation,14 mostly involve heavy synthesis, multiple steps for preparation or purification, and a lack of control over the size of both NP cores and polymer tethers. © 2014 American Chemical Society

One promising approach to prepare NBBs with defined polymer tethers is the self-collapse of individual polymer chains via intramolecular cross-linking, developed by Hawker’s group.23,24 Given a very dilute concentration, the coil-toglobule transitions driven by various intramolecular reactions only occur within individual polymer chains, to yield, so-called, single chain nanoparticles.25−39 Single chain nanoparticles with ultrafine sizes and “secondary” structures40 have attracted enormous attention due to their applications in the fields of sensing,41 catalysis,39,42 bioimaging,43 and drug delivery.44 Hawker et al. have demonstrated that the single chain polymer chemistry could be extended to linear block copolymers (BCPs) where the coil-to-globule transition only occurred within one block containing cross-linkable groups.24 This gave rise to the formation of tadpole-shaped NBB where the crosslinked block formed the “head”, attached by an un-cross-linked polymer “tail”. Zhu et al. studied that the tadpole-shaped NBBs could self-assemble in a selective solvent and form supermicellar aggregates, far different from traditional polymers.26 Chen’s group recently reported that the superparticles Received: June 29, 2014 Revised: August 16, 2014 Published: August 21, 2014 5932

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Figure 1. (a) Chemical structure and schematic illustration of polymer-tethered NBBs synthesized from the intramolecular hydrolysis/ polycondensation reaction of trimethoxysilane moieties in a linear BCP of PEO-b-P(MMA-co-TMSPMA). (b) Time-resolved GPC traces of PEO114b-P(MMA252-co-TMSPMA113) at different hydrolysis/polycondensation times: 0, 36, 72, 108, 144, 180, 216, and 720 min (from bottom to top). The polymer concentration for all GPC measurements is 0.25 mg/mL in THF. (c) Plotting of the apparent molecular weight and polydispersity index of polymers as a function of reaction time. The molecular weight and polydispersity index were calibrated using polystyrene standards.

inorganic transition of P(TMSPMA-co-MMA) block to form the hydrophobic silica-like head, thus leading to the formation of amphiphilic hybrid NBBs. The collapse of individual chains allows us to readily control the size of NBBs and the length and number of polymer tethers, as well as the relative volume of the two compartments, by tuning the polymerization degree of two blocks in linear BCP precursors. Using cutting-edge polymerization methods and design of macromolecular architectures, this approach offers us a facile synthesis of spherical NBBs, structurally analogous to surfactant molecules. We further demonstrate the molecule-mimetic self-assembly of such amphiphiles into a variety of nanostructures in selective solvents.

assembled from tadpole-shaped NBBs were ultrasoundresponsive, and the dissociation of superparticles was observed under the ultrasonic treatment.27 Zhao et al. also investigated the different self-assembly morphologies of NBBs composed of a hydrophobic coil and a charged “head”.29,37 However, experimental observations and understanding of the selfassembly uniqueness of NBBs, especially the correlation of NBB structures and their assemblies, are still lacking. In addition, most of these NBBs are composed of only organic components. The structural features of NBBs and their packing/organization are difficult to be visualized under electron microscope because of low electron density and stiffness. Herein, we report a general and facile strategy for preparing hybrid NBBs composed of silica-like heads decorated by welldefined polymer tethers. Silica NPs with controllable size/ morphology/porosity, chemical stability, and excellent biocompatibility are widely used as building blocks in material science.45,46 Our method is based on the intramolecular folding of single polymer chains using the hydrolysis and polycondensation of trimethoxysilane in di-BCPs (Figure 1a). BCPs are designed with one reactive block of poly(3(trimethoxysilyl)propyl methacrylate) (PTMSPMA) and poly(methyl methacrylate) (PMMA) (denoted as P(TMSPMA-coMMA) block) and one inert block of poly(ethylene oxide) (PEO). By dissolving such BCPs in a good solvent for both blocks at a very dilute concentration, the hydrolysis of trimethoxysilane moieties in the PTMSPMA block is triggered by the addition of ammonium hydroxide in the presence of a trace amount of water; subsequently, the further intramolecular polycondensation of silane groups to polysilsesquioxane results in the collapse of P(TMSPMA-co-MMA) blocks and the formation of silica-like NBBs. The remaining PEO block then becomes the polymer tether for NBBs. The simple hydrolysis/ polycondensation reaction would prompt the organic-to-

2. EXPERIMENTAL SECTION 2.1. Materials. Methyl methacrylate (MMA) (99%) was passed through a basic aluminum oxide column and distilled prior to use. 3(Trimethoxysilyl)propyl methacrylate (TMSPMA) (98%), N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) (>99%), copper(I) bromide (CuBr, 98%), anisole (anhydrous, 99.7%), chlorotrimethylsilane (>98%), methoxytrimethylsilane (99%), and monomethoxy poly(ethylene oxide) (PEO) (2000 g/mol (PEO45) and 5000 g/mol (PEO114)) were purchased from Sigma-Aldrich and used without further purification unless otherwise noted. Deionized water (High-Q, Inc. 103S Stills) with resistivity of >10.0 MΩ was used in all experiments. 2.2. Polymer Synthesis. Synthesis of Macroinitiator PEO-Br. 20 g of monomethoxy PEO45 (10 mmol) and 2.2 g of triethylamine (20 mmol) were first dissolved in 200 mL of anhydrous CH2Cl2. After cooling the above solution to 0 °C, a solution of 2-bromoisobutyryl bromide (3.68 g, 16 mmol) in 20 mL of CH2Cl2 was added dropwise under vigorous stirring. The reaction mixture was stirred for 2 h at 0 °C. After the solution was filtered to remove salts, the mixture was concentrated and then precipitated twice in cold diethyl ether. The PEO45 macroinitiator (PEO45-Br) was collected and dried at 40 °C under vacuum overnight.47 PEO114-Br was synthesized using a similar procedure. 5933

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Table 1. Characterizations of Linear BCPs and Polymer-Tethered NBBs polymersa

TMSPMA content (mol %)b

Mn of linear BCPs (kg/mol)c

PDI of linear BCPs

Mn of NBBs (kg/mol)c

PDI of NBBs

PEO114-b-P(MMA423-co-TMSPMA47) PEO114-b-P(MMA324-co-TMSPMA64) PEO114-b-P(MMA290-co-TMSPMA92) PEO114-b-P(MMA252-co-TMSPMA113) PEO114-b-P(MMA55-co-TMSPMA32) PEO114-b-P(MMA106-co-TMSPMA45) PEO114-b-P(MMA212-co-TMSPMA86) PEO114-b-P(MMA290-co-TMSPMA92) PEO114-b-P(MMA290-co-TMSPMA111) PEO114-b-P(MMA381-co-TMSPMA124) PEO45-b-PTMSPMA100 PEO45-b-PTMSPMA73 PEO45-b-PTMSPMA158

10 16.5 24.0 31.0 37 30.0 28.9 24.0 27.8 24.6 100 100 100

58.9 53.3 56.8 58.3 18.4 26.9 47.5 56.8 61.5 74.0 26.7 20.1 41.2

1.28 1.08 1.04 1.11 1.14 1.17 1.17 1.04 1.03 1.19 1.14 1.23 1.14

38.7 27.9 28.3 31.0 14.7 18.3 27.2 28.3 26.6 44.2 21.5 19.3 37.7

1.25 1.18 1.26 1.25 1.14 1.17 1.19 1.26 1.23 1.23 1.56 1.30 1.22

R0d 13.3 12.1 12.0 11.8 5.7 7.5 10.6 12.0 12.3 13.8

a

The repeat unit number was calculated from 1H NMR spectra using the known molecular weight of the PEO block. bThe TMSPMA content was calculated based on the repeat number of MMA and TMSPMA units in hydrophobic blocks. cThe number-average molecular weights were determined by GPC using polystyrene for calibration. dThe mean-square end-to-end distance (R0) of P(MMA-co-TMSPMA) blocks is calculated from R0 = bN0.5, where b is the Kuhn length (b = 1.5 nm for PMMA) and N is the number of Kuhn monomers.53 Synthesis of PEO-b-P(TMSPMA) by Atom Transfer Radical Polymerization (ATRP) Using Macroinitiator of PEO45-Br. CuBr (11.5 mg, 0.08 mmol), TMSPMA (2.48 g, 10.0 mmol), PEO45-Br (80.0 mg, 0.04 mmol), anisole (5.0 mL), and PMDETA (45 μL, 0.2 mmol) were added into a 20 mL of two-necked flask. The reaction mixture was degassed by three freeze−pump−thaw cycles and then filled with argon. The flask was then placed in a preheated oil bath at 60 °C for 90 min. After the polymerization, the reaction was stopped by cooling the reaction mixture to room temperature. The reaction mixture was diluted with THF and passed through a neutral Al2O3 column using THF as an eluent to remove the Cu catalysts. The polymer solution was then concentrated and precipitated in n-hexane twice. The obtained polymer was then dried at 40 °C under vacuum overnight. The final polymer products were stored in a desiccator filled with N2. From the gel permeation chromatography (GPC) measurement (polystyrene (PS) standards), the polymer was found to have an average number molecular weight (Mn,GPC) of 41.2 kg/mol and a polydispersity index (PDI) of 1.14. Synthesis of PEO-b-P(MMA-co-TMSPMA) by ATRP Using Macroinitiator of PEO114-Br. A typical procedure for the synthesis of PEO-bP(MMA-co-TMSPMA) is described below, and BCPs with different molecular weights and TMSPMA contents were prepared by varying the monomer ratios and amounts. CuBr (14.4 mg, 0.1 mmol), MMA (2.01 g, 20.0 mmol), TMSPMA (0.992 g, 4.0 mmol), PEO144-Br (0.25 g, 0.05 mmol), anisole (5.0 mL), and PMDETA (45 μL, 0.2 mmol) were added into a 10 mL two-necked flask. After the mixture was degassed by three freeze−pump−thaw cycles, the flask was placed in a 55 °C oil bath. After the polymerization proceeded for 2.5 h, the reaction mixture was diluted with tetrahydrofuran (THF) and passed through a neutral Al2O3 column using THF as an eluent to remove the catalyst. The obtained polymer solution was concentrated and precipitated in n-hexane twice. The polymer was then dried at 40 °C under vacuum overnight. The final polymer products were stored in a desiccator filled with N2. GPC analysis results show the Mn,GPC of 58.3 kg/mol and PDI of 1.11. The numbers of MMA and TMSPMA units in the P(MMA-co-TMSPMA) block calculated from the 1H NMR spectra of BCPs were 252 and 113, respectively, using the integral values of the peak at 3.92 ppm (−CH2OOC− of TMSPMA units), the peak at 3.65 ppm (−OCH2− from PEO block), and the peak at 3.60 ppm (CH3OCO− of MMA units and (CH3O)Si− of TMSPMA units). 2.3. Preparation of NBBs via an Intrachain Hydrolysis/ Polycondensation Process. In a typical experiment, PEO-bP(MMA-co-TMSPMA) (50 mg) was first dissolved in 100 mL of THF, yielding a 0.5 mg/mL polymer solution. Note that we have slightly decreased the initial concentration of polymers for BCPs with

higher molecular weights (0.2−0.5 mg/mL). The polymer solution was stirred for 2 h at room temperature. Subsequently, a mixed solution of ammonium hydroxide (10 vol % in water, 3 mL) in THF (100 mL) was added dropwise into the above solution. The intramolecular hydrolysis/polycondensation reaction was performed at room temperature for 24 h. Then, 100 μL of Me3SiOCH3 (0.72 mmol) was added to terminate the free SiOH groups on the surface of NBBs. After another 2 h, the reaction mixture was concentrated to ∼10 mL. To this solution, 100 μL of Me3SiCl (0.79 mmol) was added to further remove free −SiOH groups for 12 h.48,49 Then, polymer tethered NBBs were precipitated in n-hexane twice and separated by centrifugation at 6000 rpm. The obtained NBBs were dried at 25 °C under vacuum. 2.4. Self-Assembly of NBBs and Linear BCPs. In a typical protocol, 2.5 mg of linear BCPs or NBBs was dissolved in 0.5 mL of THF. 300 μL of distilled water was then added slowly into the solution using a 25 μL microsyringe at a rate of 25 μL/min under strong stirring. The solution was stirred for 4 h before 2 mL of distilled water was added to quench the aggregate morphologies.50 Afterward, THF was evaporated under vacuum at room temperature. 2.5. Characterizations. GPC measurements were performed on a Waters GPC-1 (1515 HPLC pump and Waters 717Plus autoinjector) equipped with a Varian 380-LC evaporative light scattering detector, a Waters 2487 dual absorbance detector, and three Jordi Gel fluorinated DVB columns (1−100K, 2−10K, and 1−500 Å). THF was used as an elution solvent at a flow rate of 2.0 mL/min, and PS standards were used for molecular weight and molecular weight distribution calibration. The data were processed using Empower GPC software (Waters, Inc.). Proton nuclear magnetic resonance (1H NMR) spectra were recorded on a Bruker Avance 300 MHz spectrometer. High resolution transmission electron microscopy (HRTEM) studies were carried out using a JEOL 2010 transmission electron microscope with an accelerating voltage of 200 kV. The TEM samples were prepared by casting the suspension of assemblies on a carbon-coated copper grid (300 mesh). Scanning electron microscopy (SEM) investigation was operated using a JEOL JSM-6330F scanning electron microscope at a voltage of 10 kV. Samples for SEM were prepared by casting one drop of the sample solution on silicon wafers and dried at room temperature. The hydrodynamic diameter of assemblies was measured on a PD4047 multitau correlator (Precision Detectors, Bellingham, MA) equipped with a 10 mW HeNe laser at a wavelength of 633 nm. The size distribution of nanoparticles was reconstructed from the correlation function of the scattered light using Precision Deconvolve (Precision Detectors) based on the regularization method by Tikhonov and Arsenin. Static light scattering (SLS) measurements 5934

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were carried out using an ALV/CGS-3 MD goniometer system, consisting of a 22 mW He−Ne laser (emitting vertically polarized light with a wavelength of 632.8 nm) and four avalanche photodiode (APD) detectors, which were equally spaced out (32° apart) on the arc of a tray driven by a goniometer. All solutions for SLS measurements were filtered through 0.22 μm Angela syringe filters (PTFE) to remove dust and kept at 23 ± 0.2 °C. SLS studies were conducted at angles between 40° and 140° with an angular step of 5°. The specific refractive index increment (dn/dc) of polymers and NBBs was determined using a DnDc-2010 differential refractometer in combination with the BI-DNDCW Software by Brookhaven Instruments Corp. The dn/dc values of linear BCPs and NBBs at 23 °C in THF are 0.087 and 0.090 mL/g, respectively.

strated that the hydrolysis and polycondensation triggered by ammonia occurred intramolecularly under the experimental conditions, as evidenced by the decrease of hydrodynamic size. Thus, the intramolecular collapse of P(MMA-co-TMSPMA) blocks leads to the formation of polymer-tethered NBBs as described below. Furthermore, the intramolecular cross-linking was confirmed using static light scattering (SLS). The Zimm plots of linear BCP and NBB of PEO114-b-P(MMA381-coTMSPMA124) are given in Figure S3. After extrapolation to both c = 0 mg/mL and θ = 0°, the absolute Mw decreased from 111.3 kg/mol (before cross-linking) to 76.1 kg/mol (after cross-linking), indicating the occurrence of intramolecular collapse of P(MMA-co-TMSPMA) blocks and the absence of intermolecular aggregation at dilute concentrations. The corresponding changes in apparent molecular weight and PDI of PEO114-b-P(MMA-co-TMSPMA) were plotted as a function of reaction time, as shown in Figure 1c. Of particular note is that the collapse of P(MMA-co-TMSPMA) blocks kinetically took place in two steps, as indicated by the two slopes for the decrease of molecular weight. This is presumably attributed to the two-step reaction of trimethoxysilane groups, namely hydrolysis and polycondensation reaction. In the first stage, the decrease of hydrodynamic volume of BCPs was immediately observed after mixing BCP solution and ammonia. The apparent molecular weight of PEO114-b-P(MMA-coTMSPMA) decreased from 58.3 to 47.1 kg/mol after mixing with ammonia hydroxide in THF solution for 36 min. This loss in molecular weight is mainly assigned to the hydrolysis of trimethoxysilane groups. Note that the complete hydrolysis of methoxy groups should theoretically reduce the molecular weight to 53.6 kg/mol. It implies that the partial polycondensation reaction is involved because ammonia hydroxide as a basic catalyst can accelerate the formation of the Si−O−Si bond.49 In the second stage, the hydrodynamic volume of BCPs further decreased due to the self-collapse of P(MMA-coTMSPMA) blocks via the polycondensation of silanol groups. The self-folding of a long chain into a specific, compact structure obviously results in a significant entropy decrease. This is counterbalanced by the polycondensation reaction, so that the self-folding of polymer chains is kinetically slow, and the apparent molecular weight of polymer chains continuously decreases over 12 h. To keep the experimental conditions constant and allow the complete collapse of all samples, the hydrolysis and polycondensation proceeded for 24 h. After the intramolecular cross-linking, the reaction was quenched by the addition of Me3SiOCH3 and Me3SiCl to remove the unreacted SiOH groups.49 The obtained polymer NBBs were quite stable in solution at a high concentration of 10 mg/mL, and no change was observed from GPC monitoring over at least two months. All samples of PEO-b-P(TMSPMA) and PEO-b-P(MMA-coTMSPMA) in Table 1 were studied for the preparation of polymer-tethered NBBs. The summarized results in Table 1 suggest that the decrease of hydrodynamic volume is dependent on the molar percentage of TMSPMA monomers and the block length of P(MMA-co-TMSPMA). First, at a low content of TMSPMA (