11284
J. Phys. Chem. B 2008, 112, 11284–11291
Chain-Length Dependence of Diblock Copolymer Micellization Kinetics Studied by Stopped-Flow pH-Jump Jingyan Zhang,†,‡ Jian Xu,† and Shiyong Liu*,† Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, UniVersity of Science and Technology of China, Hefei, Anhui 230026, China, and School of Materials and Chemical Engineering, Anhui UniVersity of Architecture, Hefei, Anhui 230022, China ReceiVed: April 28, 2008; ReVised Manuscript ReceiVed: July 1, 2008
A series of well-defined poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate) (PEO-b-PDEA) diblock copolymers containing PEO block of identical chain length and PDEA block with varying degrees of polymerization (DP, in the range of 32-154) were prepared via atom transfer radical polymerization (ATRP) employing a PEO-based macroinitiator (DP ) 113). Upon a pH-jump from 3 to 12 under highly efficient stopped-flow mixing conditions, PEO-b-PDEA copolymers spontaneously form spherical micelles of increasing sizes and aggregation numbers (Nagg) with increasing PDEA chain lengths. Stopped-flow light scattering technique was used to probe the pH-induced micellization kinetics of PEO-b-PDEA copolymers, aiming to elucidate the PDEA chain-length effects on the unimer-to-micelle transition process. Upon a stopped-flow pH-jump from 3 to 12, the obtained dynamic traces can be well-fitted with double exponential functions. The calculated fast and slow characteristic relaxation times (τ1 and τ2) can be ascribed to the formation of quasiequilibrium micelles (fast process) and subsequent relaxation into final equilibrium micelles (slow process), respectively. For PEO113-b-PDEA32 and PEO113-b-PDEA61, τ2 is almost independent of polymer concentrations, suggesting that the relaxation from quasi-equilibrium micelles into final equilibrium micelles mainly proceeds via insertion/expulsion of unimer chains. Upon increasing the DP of pH-responsive PDEA block to 89, 117, and 154, the obtained slow relaxation time, τ2, tends to decrease with increasing polymer concentrations, suggesting that the slow process is dominated by the micelle fusion/fission mechanism. The apparent activation energy (Ea) associated with τ2 has also been determined from temperature-dependent micellization kinetics for five PEO-b-PDEA copolymers. It was found that during micellization, copolymers with longer PDEA blocks exhibit much lower Ea compared to those with shorter blocks. Thus, we observed experimentally for the first time that increasing the hydrophobic block length in double hydrophilic block copolymers (DHBCs) can transform the mechanism of the slow process from unimer insertion/expulsion to micelle fusion/fission. Introduction (DHBCs)1-10
have Double hydrophilic block copolymers received ever-increasing interest in the past decade due to their promising applications in diverse fields such as drug delivery, gene therapy, interface mediators, soft actuators/valves, and catalysis.11-18 Particularly, DHBC containing a biocompatible PEO block19-23 and a pH-responsive block has been extensively investigated due to that pH variation can be readily realized both in vitro and in vivo.24 The first example of PEO-containing pH-responsive DHBC, poly(ethylene oxide)-b-poly(2-vinyl pyridine) (PEO-b-P2VP), was reported by Martin et al.25 Armes and co-workers26-30 later reported more sophisticated examples of DHBCs containing the pH-responsive poly(2-(diethylamino)ethyl methacrylate) (PDEA) building block. Some of them even exhibited “schizophrenic” micellization character, forming two or more types of structurally “inverted” micelles in aqueous solution via judicious manipulation of solution pH, temperature, and salt concentration.31-33 Concerning micellization properties of the simplest system, PEO-b-PDEA, Lee et al.34 characterized the structures of * To whom correspondence should be addressed. E-mail:
[email protected]. † University of Science and Technology of China. ‡ Anhui University of Architecture.
spherical micelles formed from PEO-b-PDEA in dilute aqueous solution as a function of pH and ionic strengths. Tan et al.35 investigated the aggregation behavior of biotinylated and nonbiotinylated PEO-b-PDEA copolymers in aqueous solution at varying pH and ionic strengths, aiming to explore their potential biomedical applications. Recently, Adams et al.19 synthesized a series of PEO-b-PDEA copolymers with relatively high polydispersity (1.36 < PDI < 1.96) and investigated their self-assembly behavior in dilute solution. Upon intentionally increasing the sample polydispersity by adjusting the polymerization conditions, they obtained a variety of self-assembled structures ranging from spherical micelles, wormlike micelles, to vesicles, which is dependent on the relative chain-length ratios. Previous reports of the self-assembly of PEO-b-PDEA copolymers mainly focused on the characterization of their final equilibrium structures by various techniques such as laser light scattering (LLS), small angle neutron scattering (SANS), and transmission electron microscopy (TEM).19,34-36 On the other hand, much less has been explored concerning the unimer-tomicelle transition kinetics, which is expected to exhibit great significance for related technological processes in practical applications. It should be noted that theoretical considerations of the micellization kinetics of diblock copolymers have been
10.1021/jp803700n CCC: $40.75 2008 American Chemical Society Published on Web 08/15/2008
Diblock Copolymer Micellization Kinetics proposed by Wang et al.,37 Dormidontova and co-workers,38-40 and Nyrkova and Semenov.41,42 However, a general consensus has not been reached yet. In the past few years, we have investigated the kinetics of unimer-to-micelle transition and structural inversion between different types of micelles for a series of stimuli-responsive DHBCs by employing the stopped-flow technique. Upon stopped-flow pH-, temperature-, and salt-jump, the timedependent scattered intensity accompanied with the evolution of micelles can be obtained. For poly(glycerol monomethacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate) (PGMA-b-PDMA-b-PDEA),43 the micellization kinetics was analyzed in the context of Dormidontova model. Upon jumping the solution pH from 4 to 12, the micellization proceeded via two successive processes. The initial fast process (τ1) is associated with the formation of quasi-equilibrium micelles, and the subsequent slow process (τ2) is attributed to micelle formation and breakup, approaching the final equilibrium state. τ2 is almost independent of copolymer concentrations, indicating that the slow process proceeds mainly via the unimer insertion/expulsion mechanism. Recently, we further investigated the effects of added salts on the pH-induced micellization kinetics. It was found that at elevated salt concentrations, the slow process associated with τ2 tends to proceed via the micelle fusion/fission mechanism.44 It is noteworthy that experimentally determining the block chain-length dependence of unimer-to-micelle transition kinetics should be very instructive.40 The results can be directly compared to those deduced from theoretical considerations, which might lead to a clearer picture concerning the mechanism of micellization kinetics. In this work, we synthesized a series of well-defined PEO-b-PDEA diblock copolymers containing identical PEO block and pH-responsive PDEA block with varying degrees of polymerization (DP, in the range of 32-154) via atom transfer radical polymerization (ATRP) employing a PEO-based macroinitiator (DP ) 113). Spherical micelles of increasing sizes can spontaneously form from PEO-b-PDEA copolymers with increasing PDEA block lengths upon a pHjump from 3 to 12 under highly efficient stopped-flow mixing conditions. The pH-induced micellization kinetics of PEO-bPDEA block copolymers has been systematically investigated so as to elucidate the effect of varying the PDEA chain length. Experimental Section Materials. 2-(Diethylamino)ethyl methacrylate (DEA, Aldrich) was vacuum-distilled from CaH2 and stored at -20 °C prior to use. Copper(I) bromide (CuBr), 2,2′-bipyridine (bpy), 2-bromoisobutyryl bromide, and monohydroxy-capped poly(ethylene oxide) (PEO113-OH, mean DP ) 113, and Mw/Mn ) 1.06) were obtained from Aldrich and used as received. PEObased ATRP macroinitiator (PEO113-Br) was synthesized by the reaction of PEO113-OH with 2-bromoisobutyryl bromide according to literature procedures.28 All other reagents were purchased from Sinopharm Chemical Reagent Co. Ltd. and used as received. Sample Preparation. PEO-b-PDEA diblock copolymers were synthesized via ATRP using PEO113-Br as the macroinitiator, and a typical procedure was as follows. A reaction flask with a magnetic stirrer and a rubber septum was charged with PEO113-Br (3.60 g, 0.72 mmol), DEA (9.4 mL, 46.8 mmol), bpy (113 mg, 0.72 mmol), and 2-propanol (12 mL). The flask was degassed by three freeze-pump-thaw cycles, back-filled with N2. CuBr (103 mg, 0.72 mmol) was added to start the polymerization at room temperature under the protection
J. Phys. Chem. B, Vol. 112, No. 36, 2008 11285 TABLE 1: Molecular Parameters of PEO113-b-PDEAm Double Hydrophilic Diblock Copolymers entry
Mna
Mwa
Mw/Mna
m, PDEAmb
fEOc
PEO113-b-PDEA32 PEO113-b-PDEA61 PEO113-b-PDEA89 PEO113-b-PDEA117 PEO113-b-PDEA154
11 700 16 500 28 400 29 600 34 200
12 200 18 300 35 800 36 400 42 400
1.04 1.11 1.26 1.23 1.24
32 61 89 117 154
0.47 0.32 0.24 0.20 0.16
a
Measured by GPC using THF as eluent. b Calculated from 1H NMR. c Volume fraction of the PEO block calculated using FPEO ) 1.13 g/cm3 and FPDEA ) 1.19 g/cm3.
of N2 flow. After 2 h, the reaction flask was quenched in liquid nitrogen, exposed to air, and diluted with 10 mL of 2-propanol. The reaction mixture was then passed through a silica gel column to remove the copper catalyst. After removing all the solvent on a rotary evaporator, the residues were dissolved in CH2Cl2 and precipitated into an excess of cold n-hexane (-70 °C) to remove residual monomers. After drying overnight in a vacuum oven at room temperature, colorless and viscous solids were obtained with a yield of ∼95%. The molecular weight and molecular weight distribution of PEO-b-PDEA diblock copolymer were determined by gel permeation chromatography (GPC) using tetrahydrofuran (THF) as the eluent: Mn ) 16 500, Mw/Mn ) 1.11. The DP of the PDEA block was determined to be 61 by 1H NMR in CDCl3, and the obtained polymer was denoted as PEO113-b-PDEA61. According to similar procedure, a series of PEO-b-PDEA copolymers with varying PDEA chain lengths were also synthesized, and their structural parameters are listed in Table 1. Self-Assembly via Stopped-Flow pH-Jump. PEO-b-PDEA copolymers were dissolved in water at pH 3 at a concentration of 4.0 g/L. Upon rapid mixing with NaOH solution on the stopped-flow device, the pH-jump from 3 to 12 can be realized in less than 1 ms. The colloidal dispersion at a final concentration of 2.0 g/L after the pH-jump was collected. It was then used for subsequent LLS and TEM analysis after further dilution. Characterization. Nuclear Magnetic Resonance Spectroscopy. All 1H NMR spectra were recorded in CDCl3 at 25 °C on a Bruker AV300 NMR spectrometer (resonance frequency of 300 MHz for 1H) operating in the Fourier transform mode. Gel Permeation Chromatography. Molecular weights and molecular weight distributions were determined by GPC equipped with Waters 1515 pump and Waters 2414 differential refractive index detector (set at 30 °C). It used a series of three linear Styragel columns HT2, HT4, and HT5 at an oven temperature of 45 °C. The eluent was THF at a flow rate of 1.0 mL/min. A series of low-polydispersity poly(methyl mathacrylate) (PMMA) standards were employed for the GPC calibration. Transmission Electron Microscopy. TEM observations were conducted on a Philips CM 120 electron microscope at an acceleration voltage of 100 kV. Samples for TEM observations were prepared by placing 10 µL of micellar solution on copper grids coated with thin films of Formvar and carbon successively. No staining was required. Laser Light Scattering. A commercial spectrometer (ALV/ DLS/SLS-5022F) equipped with a multitau digital time correlator (ALV5000) and a cylindrical 22 mW UNIPHASE He-Ne laser (λ0 ) 632 nm) as the light source was employed for dynamic LLS measurements. Scattered light was collected at a fixed angle of 90° for duration of ∼10 min. Distribution averages and particle size distributions were computed using cumulants analysis and CONTIN routines. All data were averaged over three measurements.
11286 J. Phys. Chem. B, Vol. 112, No. 36, 2008
Zhang et al.
In static LLS, we can obtain the weight-average molar mass (Mw) and the z-average root-mean-square radius of gyration (〈Rg2〉1/2 or written as 〈Rg〉) of polymer chains in a dilute solution from the angular dependence of the excess absolute scattering intensity, known as Rayleigh ratio Rvv(q), as
1 KC 1 1 + 〈Rg2 〉 q2 + 2A2C ≈ Rvv(q) Mw 3
(
)
(1)
where K ) 4π2n2(dn/dC)2/(NAλ04) and q ) (4πn/λ0) sin(θ/2) with NA, dn/dC, n, and λ0 being the Avogadro number, the specific refractive index increment, the solvent refractive index, and the wavelength of laser light in a vacuum, respectively; A2 is the second virial coefficient. The specific refractive index increment was determined by a precise differential refractometer. Also note that in this study, the sample solution was so dilute (0.1 g/L) that the extrapolation of C f 0 was not necessary, and the term 2A2C in eq 1 can be neglected. Thus, the obtained Mw should be considered as apparent values, denoted as Mw,app. Stopped-Flow with Light Scattering Detection. Stopped-flow studies were carried out using a Bio-Logic SFM300/S stoppedflow instrument. It is equipped with three 10 mL step-motordriven syringes (S1, S2, and S3), which can be operated independently to carry out single- or double-mixing. The stopped-flow device is attached to a MOS-250 spectrometer; kinetic data were fitted using the Biokine program provided by Bio-Logic. For the light scattering detection at a scattering angle of 90°, both the excitation and emission wavelengths were adjusted to 335 nm with 10 nm slits. With the use of FC-08 or FC-15 flow cells, typical dead times are 1.1 and 2.6 ms, respectively. Results and Discussion Synthesis and Self-Assembly of PEO-b-PDEA Copolymers. The controlled radical polymerization of DEA monomer has been well-established, and a variety of PDEA-containing stimuli-responsive diblock and triblock copolymers were prepared.19,28,34-36,45,46 Tan et al.35 reported the synthesis of PEOb-PDEA copolymers with or without a biotin terminal functionality via ATRP in water/methanol mixture, and the polydispersity was ∼1.3. Under different conditions, Adams et al.19 intentionally prepared PEO-b-PDEA copolymers with relatively high polydispersities (1.36 < PDI < 1.96) via ATRP in 2-butanone at 80 °C and examined the effects of relative block lengths and polydispersity on the self-assembled morphology. It seems that the solvent polarity can dramatically affect the polymerization rate and PDI.47,48 In the current study, we choose 2-propanol as the solvent, which has been proved to be an excellent solvent for DEA and 2-(dimethylamino)ethyl methacrylate (DMA) monomers;49 moreover, the polymerization of DEA and DMA in 2-propanol can effectively eliminate side reactions such as transesterification, which might occur in methanol.49 Table 1 lists the structural parameters of a series of PEO-b-PDEA copolymers with PDI in the range of 1.04-1.26. Previous investigations suggested that the polydispersity of block copolymers can exhibit dramatic effects on the morphology of final aggregates.50-52 Terreau et al.51 studied the selfassembly of a series of polystyrene-b-poly(acrylic acid) (PSb-PAA) diblock copolymers of increasing polydispersity for the PAA block. They found that at relatively high water content, the self-assembled morphology can range from spheres, rods, to vesicles depending on the PDI of PAA block. For a series of PEO-b-PDEA copolymers with relatively broad polydispersity, Adams et al.19 observed the evolution of self-assembled morphology with the volume fraction of PEO block (fEO),
TABLE 2: Dynamic and Static LLS Characterization of Micelles Prepared from PEO113-b-PDEAm Diblock Copolymers via Stopped-Flow Mixinga entry PEO113-b-PDEA32 PEO113-b-PDEA61 PEO113-b-PDEA89 PEO113-b-PDEA117 PEO113-b-PDEA154
〈Rh〉 〈Rc〉 (nm)b µ2/Γ2 b (nm)c 11 13 14 16 19
0.11 0.09 0.07 0.12 0.14
2 4 5 7 10
Mw,app (g/mol)d 4.02 × 105 7.76 × 105 1.18 × 106 1.86 × 106 3.63 × 106
F Nagge (g/cm3)f 35 43 44 57 87
0.12 0.14 0.17 0.18 0.17
a The micellar solution was prepared via pH-jump from 3 to 12 upon stopped-flow mixing of unimer solutions at pH 3 with NaOH solution. b Determined by dynamic LLS at a scattering angle of 90° and a polymer concentration of 2.0 g/L; the estimated error associated with each value was (2 nm. c The average radii of insoluble PDEA cores, 〈Rc〉, were estimated from the scaling law proposed by Wu and Gao (ref 55), assuming that PEO corona of all PDEA-core micelles occupy the same brush thickness. d The apparent molar masses, Mw,app, of micelles were determined by static LLS at a concentration of 0.1 g/L. e Calculated as Nagg ) Mw,app/Mw, where Mw is the weight-average molecular weight of PEO113-bPDEAm diblock copolymers. f Calculated as F ) Mw,app/(4π/ 3NA〈Rh〉3), where NA is the Avogadro number.
forming spherical micelles, rodlike micelles, and vesicles at high, intermediate, and low (
