Aggregation Behavior of Doubly Thermoresponsive Polysulfobetaine

Article pubs.acs.org/Macromolecules

Aggregation Behavior of Doubly Thermoresponsive Polysulfobetaine‑b‑poly(N‑isopropylacrylamide) Diblock Copolymers Natalya S. Vishnevetskaya,† Viet Hildebrand,‡ Bart-Jan Niebuur,† Isabelle Grillo,§ Sergey K. Filippov,∥ André Laschewsky,*,‡,⊥ Peter Müller-Buschbaum,† and Christine M. Papadakis*,† †

Fachgebiet Physik weicher Materie/Lehrstuhl für Funktionelle Materialien, Physik-Department, Technische Universität München, James-Franck-Straße 1, 85748 Garching, Germany ‡ Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam-Golm, Germany § Large Scale Structures Group, Institut Laue-Langevin, 71 avenue des Martyrs, CS 20156, 38042 Grenoble, Cedex 9, France ∥ Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 16206 Prague 6, Czech Republic ⊥ Fraunhofer Institut für Angewandte Polymerforschung, Geiselbergstr. 69, 14476 Potsdam-Golm, Germany S Supporting Information *

ABSTRACT: A 2-fold thermoresponsive diblock copolymer PSPP430-b-PNIPAM200 consisting of a zwitterionic polysulfobetaine (PSPP) block and a nonionic poly(N-isopropylacrylamide) (PNIPAM) block is prepared by successive RAFT polymerizations. In aqueous solution, the corresponding homopolymers PSPP and PNIPAM feature both upper and lower critical solution temperature (UCST and LCST) behavior, respectively. The diblock copolymer exhibits thermally induced “schizophrenic” aggregation behavior in aqueous solutions. Moreover, the ion sensitivity of the cloud point of the zwitterionic PSPP block to both the ionic strength and the nature of the salt offers the possibility to create switchable systems which respond sensitively to changes of the temperature and of the electrolyte type and concentration. The diblock copolymer solutions in D2O are investigated by means of turbidimetry and small-angle neutron scattering (SANS) with respect to the phase behavior and the self-assembled structures in dependence on temperature and electrolyte content. Marked differences of the aggregation below the UCST-type and above the LCST-type transition are observed. The addition of a small amount of NaBr (0.004 M) does not affect the overall behavior, and only the UCST-type transition and aggregate structures are slightly altered, reflecting the well-known ion sensitivity of the zwitterionic PSPP block.

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INTRODUCTION Water-soluble thermoresponsive polymers are a subclass of stimuli-sensitive polymeric systems (often referred to as “smart materials”), which can undergo dramatic changes of their properties in response to small changes of temperature.1−3 Such polymers are promising for a number of applications, e.g., chromatography,4−6 smart surfaces,7−9 or biomedical applications including drug or gene delivery and tissue engineering.10−13 In most aqueous thermosensitive polymeric solutions, a reversible coil−globule collapse transition of the macromolecules takes place at the phase separation temperature.14 A lower critical solution temperature (LCST) or upper critical solution temperature (UCST) behavior can be found, depending on whether the miscibility gap occurs at high or low temperatures. In the case of LCST behavior, the chains are well-hydrated by water molecules at low temperatures and exhibit an expanded conformation, whereas, above the transition temperature, they collapse along with a partial © XXXX American Chemical Society

release of the water molecules, forming, when applicable, new intra- and interchain H-bonds.15,16 The collapsed chains form compact globules which subsequently aggregate, causing turbidity.17 Vice versa, in the case of polymers exhibiting UCST behavior, the polymer chains undergo a phase transition from an expanded well-hydrated state to a collapsed and mostly dehydrated state upon cooling.18 A number of fundamental studies have focused on thermoresponsive systems with a single phase transition (and, hence, a single cloud point), the vast majority addressing polymers that show a LCST in water.3,16 Much less work has been devoted to UCST-type polymers, even though they can be analogously exploited for their thermoresponsive behavior.18−21 Although the use of thermoresponsive block copolymers in addition to such homo- and Received: June 3, 2016 Revised: July 29, 2016

A

DOI: 10.1021/acs.macromol.6b01186 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

instance, the latter were incapable of solubilizing a hydrophobic dye.35 Polysulfobetaines provide chemically and structurally welldefined polymers which are well-suited as model systems. Nevertheless, zwitterionic block copolymers are not the only option to form schizophrenic micellar systems. Among the nonionic, water-soluble polymers with UCST behavior are described in the literature polymers like poly(ethylene oxide),58,59 poly(vinyl methyl ether),60,61 hydrophobically modified poly(vinyl alcohol),62 and poly(hydroxyethyl methacrylate).63 However, the UCSTs of these polymers are either below 0 °C or above 100 °C, and information on their properties is scarce.18 Moreover, only few data are available on the diblock copolymers consisting of an uncharged UCST block and LCST block, which allow up to now only limited deductions.44,64−66 In the present work, we investigate the aggregation of a diblock copolymer PSPP430-b-PNIPAM200 (Figure 1) in D2O in

statistical copolymers has opened a number of opportunities for smart behavior,22,23 studies have been mostly limited to simple “on−off” systems, where the polymers undergo a transition from the molecularly dissolved state to the aggregated state or vice versa, exhibiting either a LCST or a UCST for one of the blocks.2,3,10,11,24,25 Much less studied are systems in which a direct transition between two different self-assembled superstructures takes place23,26 as well as complex responsive systems in which two thermal transitions proceed subsequently via two LCST-type transitions, e.g., transitions from the molecularly dispersed state to one superstructure and then to another superstructure.22,27−32 It seems particularly attractive to combine two different switching behaviors, namely UCST and LCST behavior, in order to obtain a structure inversion (“schizophrenic” behavior).33 The transformation proceeds via an intermediate stage, which may be either insolubility or the molecularly dissolved state, depending on the relative positions of the two phase transitions.28,29,34−45 In the present study, we focus on the combination of UCST and LCST switching behavior in diblock copolymers containing one block with UCST and one block with LCST behavior, respectively, revisiting the originally reported system design that combined the polysulfobetaine poly(N,N-dimethyl-N-(3(methacrylamido)propyl)ammoniopropanesulfonate) (PSPP) with the nonionic poly(N-isopropylacrylamide) (PNIPAM). In fact, PNIPAM is by far the most studied thermoresponsive polymer with LCST behavior, which exhibits a sharp collapse transition at ∼32 °C.16,17,46−51 The UCST behavior of the permanently zwitterionic PSPP was recently studied in detail.52−54 It depends sensitively on the molar mass and even more on the type and concentration of added low molar mass electrolytes.53,54 The strongest effects on its UCST were typically found for chaotropic anions53,54 in agreement with the Hofmeister series,55,56 increasing in the order SO42− < Cl− < Br−. The salt effects are complex, though: At low salt concentrations, the UCST increases with the amount of added salt. It passes through a maximum, beyond which it continuously decreases. For NaBr, the maximum is found at about 0.004 M for PSPP solutions in D2O.53 This salt dependence of the UCST offers the possibility to create orthogonally switchable systems, when combining with a thermoresponsive block, which responds sensitively to both temperature changes and changes of the electrolyte type and concentration.28,57 Moreover, the phase transition temperature of PSPP has recently been shown to be significantly higher in heavy water, D2O, than in normal water, H2O.53 The studies carried out previously on diblock copolymers of PSPP and PNIPAM with low to moderate molar masses (10 000 and 50 000 g/mol) were performed mostly in H2O at high dilution and focused on proving the occurrence of two transitions with subsequent polymer aggregation using 1H NMR, turbidimetric, viscometric, and DLS studies.35,57 Moreover, the effect of NaBr was demonstrated for a few selected concentrations of the diblock copolymers in water, which suppressed the UCST transition completely, while the LCST transition temperature was only reduced slightly. Interestingly, qualitative solubilization experiments suggested that the presumed micellar aggregates formed by the collapse of the PNIPAM block at elevated temperatures exhibit core properties which are markedly different from the ones of the aggregates formed by the collapse of the PSPP block at low temperatures. For

Figure 1. Chemical structure of the diblock copolymer under investigation, PSPPm-b-PNIPAMn (m = 430, n = 200).

a broad temperature range. In addition to turbidimetry, dynamic light scattering (DLS) and small-angle neutron scattering (SANS) have been used to elucidate the mesoscopic structures in detail. Compared to the PSPP-b-PNIPAM block copolymers used in the earlier studies,35,57 the polymer under investigation has much larger block lengths. The zwitterionic block is relatively long (m = 430), and the nonionic block has half of the size (n = 200) of the zwitterionic block, bearing additionally an aminonaphthalimide fluorescence tag as an end group. In H2O, the homopolymers with similar degrees of polymerization exhibit an UCST-type transition at ca. 25 °C and a LCST-type transition at ca. 32 °C; i.e., the temperature gap between the two transitions is much smaller than for the analogues studied previously.35,57 Studies have been performed in pure D2O as well as in dilute solutions of NaBr (0.004 M) in D2O. At this specific concentration of NaBr, it has previously been shown that the effect on the UCST of PSPP in aqueous solution is maximum, namely, an increase by about 10 K compared to saltfree H2O.53 Thus, three regimes are expected in dependence on temperature and electrolyte concentration (Figure 2): (I) below the UCST-type transition of PSPP, micelles with a PSPP core and a PNIPAM shell; (II) between the UCST-type transition of PSPP and the LCST-type transition of PNIPAM, unimers, i.e., molecularly dissolved polymers, and (III) above the LCST transition of PNIPAM, inverted micelles with a PNIPAM core and a PSPP shell. We have combined turbidimetry to map the phase behavior and to locate the cloud points with small-angle neutron scattering (SANS) to obtain detailed structural information. Dynamic light scattering (DLS) in backscattering geometry confirmed the overall behavior. B


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Macromolecules

amidopropyl)ammoniopropanesulfonate (SPP, 5.0 g, 17 mmol), (R)2-(6-(dimethylamino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl 4-cyano-4-(((phenethylthio)carbonothioyl)thio)pentanoate (CTA, 0.018 g, 2.9 × 10−2 mmol), and 4,4′-azobis(4-cyanopentanoic acid) (V501, 0.0020 g, 5.8 × 10−3 mmol) were dissolved in trifluoroethanol (10 mL). The yellow reaction mixture was purged with N2 for 30 min and subsequently polymerized at 75 °C for 15 h. The mixture was precipitated into methanol (repeated 3 times), and the polymer was isolated and dried under high vacuum. Homopolymer PSPP was obtained as amorphous yellow solid (yield 3.1 g, 62%). 1 H NMR (300 MHz, in dilute aqueous NaCl (0.9 g L−1) in D2O, 298 K): δ (ppm) = 0.8−1.9 (broad 5H, −CH3 and −CH2− on/in backbone), 1.9−2.3 (4H, −CH2−C−N+−C−CH2−), 2.9−3.0 (2H, −CH2−SO3), 3.0−3.3 (6H, ⟩N+(CH3)2, 3.3−3.6 (6H, −CH2−N+− CH2−, CON−CH2−). FT-IR (selected bands, cm−1): 3446 ν(NH), 1645 ν(amide I), 1539 ν(amide II), 1195, and 1043 ν(SO3−). Maximum absorbance (UV−vis) in trifluoroethanol λmax = 260, 294, and 442 nm and in water λmax = 258, 297, and 447 nm. Emission maxima of fluorescence spectra in trifluoroethanol λPL = 537 nm and in water λPL = 546 nm. Synthesis of Poly(N-isopropylacrylamide), PNIPAM. N-Isopropylacrylamide (NIPAM, 1 g, 9 mmol), (R)-2-(6-(dimethylamino)-1,3dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl 4-cyano-4(((phenethylthio)carbonothioyl)thio)pentanoate (CTA, 0.03 g, 0.05 mmol), and 4,4′-azobis(4-cyanopentanoic acid) (V501, 0.003 g, 9.0 × 10−3 mmol) were dissolved in trifluoroethanol (2 mL). The yellow solution was purged with N2 for 30 min and subsequently polymerized at 75 °C for 6 h. The yellow reaction mixture was precipitated into diethyl ether, and the homopolymer was isolated and dried under high vacuum. The purified PNIPAM was obtained as yellow solid (yield 0.95 g, 95%). 1 H NMR (300 MHz, D2O, 298 K): δ (ppm) = 0.9−2.1 (broad 9H, −CH3, −CH2−, and −CH− of the backbone), 3.9−4.0 (1H, −C− CH−C−). FT-IR (selected bands, cm−1): 3461 and 3316 ν(NH), 2973, 2936, and 2879 ν(C−H), 1652 ν(amide I), 1540 ν(amide II), 1457 ν(NH). Maximum absorbance (UV−vis) in trifluoroethanol λmax = 302 and 442 nm and in water λmax = 305 and 447 nm. Emission maxima of fluorescence spectra in trifluoroethanol λPL = 537 nm and in water λPL = 546 nm. Synthesis of Poly(N,N-dimethyl-N-(3-methacrylamidopropyl)ammoniopropanesulfonate-block-N-isopropylamide), PSPP-b-PNIPAM. N-Isopropylacrylamide (NIPAM, 0.1 g, 0.8 mmol), poly(N,Ndimethyl-N-(3-methacrylamidopropyl)ammoniopropanesulfonate) (macro-CTA, 0.5 g, 4.0 × 10−3 mmol), and 4,4′-azobis(4-cyanopentanoic acid) (V501, 2.0 × 10−4 g, 8.5 × 10−4 mmol) were dissolved in trifluoroethanol (3.5 mL). The solution was purged with N2 for 30 min and subsequently polymerized at 75 °C for 24 h. The reaction mixture was precipitated into diethyl ether (repeated three times); the block copolymer was isolated and dried under high vacuum. PSPP-bPNIPAM was obtained as yellow solid (yield 0.4 g, 80%). 1 H NMR (300 MHz, in dilute aqueous NaCl (0.9 g L−1) in D2O, 298 K): δ (ppm) = 0.8−2.5 (broad 17H, −CH3 and −CH2− on/in backbone of SPP and NIPAM, and 4H, −CH2−C−N+−C−CH2), 2.9−3.1 (2H, −CH2−SO3), 3.1−3.3 (6H, ⟩N+(CH3)2, 3.3−3.7 (6H, −CH2−N+−CH2−, CON−CH2−), 3.8−4.1 (1H, −C−CH−C−). FTIR (selected bands, cm−1): 3446 ν(NH), 1645 ν(amide I), 1539 ν(amide II), 1195 and 1043 ν(SO3−). Maximum absorbance (UV−vis) in trifluoroethanol λmax = 297 and 442 nm and in water λmax = 297 and 447 nm. Emission maxima of fluorescence spectra in trifluoroethanol λPL = 537 nm and in water λPL = 546 nm. Sample Preparation for Structural Characterizations. Polymer solutions were prepared in salt-free D2O or in 0.004 M NaBr solution in D2O. The polymer concentrations were 10−50 g L−1 for turbidimetric measurements and 50 g L−1 for SANS. All polymer solutions were equilibrated for about 2 days in a thermoshaker at 25 °C, i.e., in regime II. Methods. Characterization during Synthesis. 1H nuclear magnetic resonance (NMR) spectra were recorded with a Bruker Avance 300 spectrometer (300 MHz) at ambient temperature in D2O or dichloromethane. The solvent signals were set to 4.79 ppm (trace

Figure 2. Phase behavior expected for PSPP-b-PNIPAM in aqueous solution in dependence on temperature and electrolyte concentration: (I) micelles with a PSPP core (red) and a PNIPAM shell (blue), (II) unimers, and (III) micelles with a PNIPAM core and a PSPP shell. The UCST-type transition of PSPP is depicted by the lower dashed red line and the LCST of PNIPAM by the upper dash-dotted blue line. The UCST-type transition is expected to be more strongly dependent on electrolyte concentration than the LCST-type transition.57

The system presented here offers numerous perspectives for the creation of orthogonally and double switchable polymer solutions due to an abundance of variations of the properties of the two blocks as well as the block lengths. For instance, the chemical structure of the spacer group separating the ammonium and the sulfonate groups in polysulfobetaine strongly affects the phase transition temperature.54 Apart from the well-established zwitterionic monomers such as 3((3-methacrylamidopropyl)dimethylammonio) propane-1-sulfonate (SPP), the closely related monomers 2-hydroxy-3-((3methacrylamidopropyl) dimethylammonio)propane-1-sulfonate (SHPP) and 4-((3-methacrylamidopropyl)dimethylammonio)-butane-1-sulfonate (SBP) may be used. Moreover, the thermoresponsive PNIPAM block may be replaced by poly(N-isopropylmethacrylamide) (PNIPMAM). Its additional methyl group has a strong effect on the cloud point as well as on its dependence on ionic strength.47,50,67 This way, the cloud points and their dependence may be tuned. Orthogonally switchable diblock copolymers can be designed which switch from micelles with a nonionic shell and a polysulfobetaine core at low temperatures to the reverse micelles at high temperatures by an intermediate state, which may be either the molecularly dissolved polymers or large aggregates/macroscopic precipitates in the intermediate temperature range. The detailed phase diagram depends on the block lengths, the chemical structures of the two blocks, and the presence of electrolyte.

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EXPERIMENTAL SECTION

Materials. General Chemicals and Solvents. Chain transfer agent (R)-2-(6-(dimethylamino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)yl)ethyl 4-cyano-4-(((phenethylthio)carbonothioyl)thio)pentanoate was synthesized as described elsewhere.53 4,4′-Azobis(4-cyanopentanoic acid) (V501, Wako) was crystallized from methanol, and N-isopropylacrylamide (NIPAM, TCI, 98%) was crystallized from hexane. N,N-Dimethyl-N-(3-methacrylamidopropyl)ammoniopropanesulfonate (SPP) was kindly donated by Raschig, Ludwigshafen, Germany. Diethyl ether (VWR, 100%), methanol (Avantor, 99.8%), trifluoroethanol (Roth, 99.8%), sodium bromide (ChemSolute, 99%), deuterated water (D2O, Armar, 99.9 atom % D for synthesis and characterization during synthesis, Deutero GmbH, purity 99.98% for structural characterizations), and dichloromethane-d2 (CD2Cl2, Armar, 99.5 atom % D) were used as received. Water was purified by a Millipore Milli-Q Plus water purification system (resistivity 18 MΩ cm−1). Synthesis of Poly(N,N-dimethyl-N-(3-methacrylamidopropyl)ammoniopropanesulfonate) PSPP. N,N-Dimethyl-N-(3-methacrylC


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Macromolecules water) and 5.32 ppm, respectively. 1H NMR spectra of the crude reaction mixtures were used to calculate the conversions by comparing the integral of the signals of the olefin double bond to the integral of the signals of the ammonium group or isopropyl group, respectively. Infrared spectra were taken from KBr pellets using a FT-IR spectrometer IFS 66/s (Bruker). Fluorescence spectra were recorded by a PerkinElmer luminescence spectrometer LS 50 B. Ultraviolet− visible (UV−vis) absorption spectra were recorded by a UV/vis/NIR spectrometer Lambda instrument (PerkinElmer). Number-average molar masses of the polymers were determined by UV−vis end-group analysis using the respective ε values, assuming that every polymer carries one naphthalimide chromophore moiety.53 For the diblock copolymer, the number-average molar mass was verified by comparing the integrals of the signals characteristic for the blocks with each other, assuming that the molar mass of the PSPP block is identical to the one of the macroCTA engaged. Theoretically expected number-average molar masses, Mntheo, are calculated according to c M ntheo = M conversion × MCRU + MCTA cCTA (1)

Modeling of the SANS Curves. In regimes I and II, the SANS curves are analyzed using a simple model that reproduces the main characteristic features of the scattering intensity curves, I(q): I(q) = IAgg(q) + Isolv(q) + Ibkg

(2)

The first term, IAgg(q), is used to describe the low-q scattering due to large aggregates, Isolv(q) is the so-called solvation term, which is used to describe the high-q scattering, and Ibkg is the incoherent background. These are described in detail below. Because of the limited q-range, the size of the large clusters cannot be completely resolved and is therefore is approximated by a modified Porod term, which reads69

IAgg(q) =

Ip qα

(3)

where IP is a scaling factor. α is the Porod exponent, which characterizes the surface roughness of the aggregates: α = 4 is obtained for particles with a smooth surface, whereas α < 4 points to rough surfaces and α > 4 to a concentration gradient near the aggregate surface.70,71 Isolv(q) originates from the concentration fluctuations in semidilute polymer solutions and is governed by the solvation (hydration) of the polymer chains:72

where MCRU is the molar mass of the constitutional repeat unit, MCTA the molar mass of the RAFT agent, cM the molar concentration of the monomer, and cCTA the molar concentration of the RAFT agent. Turbidimetry. The cloud points were determined by turbidimetry using a Varian Cary 50 UV−vis spectrometer from Varian Inc., Palo Alto, CA, equipped with a single cell Peltier thermostat for the temperature control. A quartz glass cell from Hellma Analytics with a light path of 10 mm was used. The solutions were either cooled from regime II (25 °C) to regime I or heated from regime II to regime III. All transmittance measurements were performed at a wavelength of 500 nm during heating/cooling runs in steps of 0.5 K with a thermal equilibration time at each temperature of 5 min. The diblock copolymer PSPP430-b-PNIPAM200 was measured in pure D2O and in 0.004 M NaBr in D2O. The data were normalized to the absorption of the solvent-filled cell, whose transmittance was set to 100%, i.e., zero absorption. The cloud points CPUCST and CPLCST were taken as the temperatures where the transmission had decreased by 5% from the value in regime II. The cloud point of the homopolymer PSPP430 was determined using Varian Cary 50 Scan UV−vis spectrometer, equipped with a single cell Peltier thermostat, using an optical silica cuvette with a light path of 10 mm. Measurements were performed at a wavelength of 800 nm during heating/cooling runs in steps of 0.1 K with an equilibration time at each temperature of 12 s. The solution was heated above the phase transition temperature and stirred prior to measurement. The cloud point was taken as the temperature where the normalized transmittance of the solution in the cooling runs was reduced to 95%. Small-Angle Neutron Scattering (SANS). SANS experiments were performed at the instrument D11 at the Institut Laue-Langevin (ILL) in Grenoble, France. The incident neutrons had a wavelength λ = 6.0 Å with a spread of 9%. A 3He gas detector with an area 96 × 96 cm2 and a pixel size of 7.5 × 7.5 mm2 was used. The momentum transfer q is q = 4π × sin(θ/2)/λ with θ being the scattering angle. A q-range from 0.002 to 0.52 Å−1 was covered. Samples were mounted in quartz glass cells from Hellma Analytics with a neutron light path of 1 mm. At the end of each run, the sample transmission was measured. Boron carbide was used for measurement of the dark current and H2O for the detector sensitivity and calibration of the intensity. The scattered intensity curves were azimuthally averaged and corrected for background scattering from the solvent-filled cell and parasitic scattering. The data were reduced using the software LAMP.68 The diblock copolymer PSPP430-b-PNIPAM200 was measured in pure D2O and in 0.004 M NaBr in D2O. Measurements were performed while heating from 15 to 50 °C in steps of 7−10 K, using a copper sample holder with 10 positions and an inner flow circuit, which was connected to a thermostat. After each temperature change, a thermal equilibration time of 15 min was applied. The measuring times were 40, 6, and 5 min at the sample−detector distances (SDDs) of 34.00, 7.99, and 1.20 m, respectively.

Isolv(q) = CFsolv(q)

(4)

The parameter C characterizes the solvation intensity, which reads

C=A

kBT (Δρ)2 K

(5)

where A is a scaling factor related to the volume fraction, K is the osmotic compressibility, (Δρ)2 is the contrast factor with ρ being the scattering length densities of the chains and the solvent, kB is Boltzmann’s constant, and T is the absolute temperature. F(x) is the scaling function, which is given by a modified Ornstein−Zernike function: Fsolv(q) =

1 1 + (|q − q0|ξ)m

(6)

m is the solvation Porod exponent. For noncharged polymers, m = 5/3 is expected for a polymer coil in a good solvent, while m = 2 corresponds to a Gaussian coil in a theta solvent.73 ξ is a correlation length or mesh size. q0 is the peak position: if applicable, it corresponds to an average distance d0 = 2π/q0 between the charged domains. d0 is finite for solutions of charged polymers and zero for neutral polymer solutions. The following model function was used to describe the SANS curves of the diblock copolymer PSPP430-b-PNIPAM200 solution in regime III and in regime I (as an alternative to eq 2, to gain more detailed structural information):

I(q) = I0P(q)SHS(q) + IAgg(q) + IOZ(q) + Ibkg

(7)

I0 is a scaling factor, P(q) the form factor of the micelles, and SHS(q) the hard-sphere structure factor. IOZ(q) is the Ornstein−Zernike term, IAgg(q) describes scattering from large aggregates, and Ibkg is the incoherent background. These contributions are described in detail below. Different functions were used for P(q), namely the form factor of polydisperse, homogeneous spheres, Psphere(q) in regime I, or the form factor of polydisperse spherical particles with a core−shell structure, Pcore−shell(q), in regime III. The form factor of polydisperse, homogeneous spheres, Psphere(q), is given by74 Psphere(q) =

⎛ 4π ⎞2 2 ⎜ ⎟ N (Δρ) ⎝ 3 ⎠ 0

∫0

∞

f (r )r 6F 2(q) dr

(8)

where N0 is the total number of particles per unit volume. Δρ is the difference in scattering length density of the sphere and the solvent: D


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Macromolecules Δρ = ρsphere − ρsolvent (values used see below). f(r) is the normalized Schulz distribution:75

f (r ) = (z + 1)z + 1u z

exp[− (z + 1)u] r avg Γ(z + 1)

values for PNIPAM and PSPP and the penetration of D2O into the micellar shells, the SLD values of the sphere, ρsphere in eq 5, were kept in the range (0.79−1.35) × 10−4 nm−2. In the case of core−shell structures (eq 8), taking into account the density gradient from surface to the central part of the micelles, together with the above-described reasons, the SLD values were kept in the order ρcore < ρshell < ρD2O, namely (0.8−1.5) × 10−4 nm−2 for ρcore, (1.5−5.0) × 10−4 nm−2 for ρshell, and 6.34 × 10−4 nm−2 for ρD2O. The SANS curves were modeled using the SANS Data Reduction and Analysis software provided by the NIST Center for Neutron Research within the IGOR Pro software environment.80

(9)

u = r/ravg, where ravg denotes the average radius, Γ(n) is the Gamma function, and z is related to the polydispersity by z = 1/(p2 − 1). p = σ/ravg, where σ2 is the variance of the distribution. F(q) is the scattering amplitude of a sphere having a radius r:

F(q) =

3[sin(qr ) − qr cos(qr )] (qr )3

■

(10)

RESULTS The section is structured as follows: First, the design of the diblock copolymers is explained. Then, we discuss the behavior of the cloud points for the homopolymer and diblock copolymer in salt-free solution and in the presence of electrolyte, as determined using turbidimetry. Subsequently, the structural studies with SANS in salt-free solution and in the presence of electrolyte are discussed. Finally, the results are summarized. Polymer Design. The doubly thermoresponsive diblock copolymer has been designed to feature both an UCST- and a LCST-type phase transition in aqueous solution, where especially the UCST may be tuned by electrolyte addition. The two transition temperatures in salt-free solution are aimed at being close to each other. In particular, we speculated whether in such a system the salting-in effect upon appropriate NaBr addition might result in an overlap of the two transition processes. As the UCST of PSPP increases notably with molar mass,53 a block copolymer with a relatively long PSPP block together with a shorter PNIPAM block has been synthesized, namely PSPP430-b-PNIPAM200. Different from the first “schizophrenic” block copolymers studied based on PSPP and PNIPAM, which were synthesized in the early days of the RAFT polymerization technology,35 in the present study, the block sequence was chosen as PSPP-b-PNIPAM in order to enhance the blocking efficiency.81 Moreover, a RAFT agent has been chosen that is well-suited for polymerizing methacrylic monomers and that has been additionally labeled with a fluorescent dye via the R-group. This end-group label serves not only as a tracer but also facilitates the a priori difficult molar mass analysis of amphiphilic and zwitterionic block copolymers.53,54 The polymer characteristics are compiled in Table 1. Phase Behavior. The cloud point, CPUCST, of a 50 g L−1 solution of the homopolymer PSPP430 in salt-free D2O has been determined via turbidimetry during a cooling run (not shown). It was found at CPUCST (PSPP430) = 29.6 ± 0.5 °C. The cloud

The form factor of a core−shell particle, Pcore−shell(q), having a polydisperse core and a uniform shell thickness,76 reads

Pcore ‐ shell(q) =

Fcore − shell(q) = +

1 ⟨Vmic⟩

∫0

∞

f (rcore)Fcore − shell 2(q) dr

(11)

3Vcore(ρcore − ρshell )j1 (qrcore) qrcore

3Vmic(ρshell − ρsolv )j1 (qrmic) qrmic

(12)

where j1(x) = (sin x − x cos x)/x and the micellar radius, rmic, is the sum of the core radius, rcore, and the shell thickness, t: rmic = rcore + t. The form factor is normalized by the average micelle volume ⟨Vmis⟩ = 4π⟨rmis3⟩/3. The function f(rcore) is the normalized probability of finding a particle with a core radius between rcore and rcore + dr, and it accounts for the polydispersity of the cores according to a Schultz distribution (eq 9). The polydispersity of the core radius is pcore = σ/ rcore. The correlation between the particles is modeled by the hard-sphere structure factor SHS(q) using the Percus−Yevick approximation:77 2

SHS(q) =

1 1 + 24ηG(2RHSq)/2RHSq

(13)

where RHS is the hard-sphere radius, i.e., half the center-to-center distance between the particles. η is the hard sphere volume fraction, i.e., the fraction of micelles that are correlated, and

2x sin x + (2 − x 2) cos x − 2 sin x − x cos x + δ x2 x3 4 2 3 − x cos x + 4(3x − 6 cos x + (x − 6x) sin x + 6) +ε x5 (14) where G(x) = γ

γ = (1 + 2η)2 /(1 − η)4 , ε = γη/2

δ = − 6η(1 + η/2)2 /(1 − η)4 , (15)

The Ornstein−Zernike (OZ) term describes the concentration fluctuations in semidilute polymer solutions and the correlation length or mesh size ξ.78 It reads

IOZ(q) =

Table 1. Molecular Characteristics of the Polymers Studied Mn [g/mol]

IOZ 2 2

1+qξ

(16)

where IOZ is the scaling factor. For IAgg(q), again the modified Porod term was used (eq 3). The incoherent background was fixed at 0.06 cm−1. The scattering length density (SLD) of D2O, ρD2O = 6.34 × 10−4 nm−2, was taken from the literature.79 The SLD value of the 0.004 M NaBr solution in D2O was calculated as 6.22 × 10−4 nm−2. The SLD values of the components of our systems were calculated using the mass densities, namely, 1.1 g cm−3 for PNIPAM and assuming 1.0 g cm−3 for PSPP. The following values are obtained: ρPNIPAM = 0.81 × 10−4 nm−2 and ρPSPP ≈ 0.79 × 10−4 nm−2. According to the similarity of the SLD

polymer

theoretically expecteda

via 1H NMRb

by end-group analysisc

PSPP430d PSPP430-b-PNIPAM200

127 000 150 000

149 000

113 000 152 000

a

Calculated from monomer conversion and molar ratios of monomer and CTA. bCalculated from the relative signal intensities of the 1H NMR signals of the PSPP and PNIPAM blocks, assuming that the molar mass of the PSPP block is the same in the macroRAFT and in the block copolymer. cBased on the UV/vis absorbance band at 442 nm of the R group. dEmployed as macro CTA in the synthesis of the block copolymer. E


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the CPUCST of PSPP depends on the polymeric architecture and is altered by the presence of the second block, whereas the CPLCST of PNIPAM is unaffected by the second block. The CPUCST and CPLCST values of PSPP430-b-PNIPAM200 in dependence on polymer concentration in salt-free D2O and in 0.004 M NaBr solution in D2O are shown in Figure 3b. Both cloud points depend on the polymer concentration: In salt-free solution, CPUCST increases from 18.0 ± 0.5 °C at 10 g L−1 to 21.2 ± 0.5 °C at 50 g L−1, whereas CPLCST slightly decreases from 33.4 ± 0.5 °C to 32.3 ± 0.5 °C in the same concentration range. In 0.004 M solutions of NaBr in D2O, the values of CPUCST are slightly higher, with the difference decreasing from 1.2 ± 0.5 K at 10 g L−1 to 0.6 ± 0.5 K at 50 g L−1. This increase of the CPUCST value in dilute salt solutions of PSPP430-bPNIPAM200 is smaller than expected according to the previous studies of the PSPP in aqueous solutions,53 namely an increase by about 10 K. Thus, CPUCST of PSPP is sensitive to the presence of the PNIPAM block, to ionic strength, and to concentration. In contrast, CP LCST is only marginally concentration-dependent and is not sensitive to the presence of salt either. The cloud points of a 50 g L−1 solution of PSPP430-b-PNIPAM200 in 0.004 M NaBr in D2O were found as CPUCST = 21.8 ± 0.5 °C and CPLCST = 32.3 ± 0.5 °C, respectively. Structural Investigations of the Self-Assembled Structures Using SANS. A detailed structural characterization of the 50 g L−1 solution of the diblock copolymer PSPP430-bPNIPAM200 has been carried out using temperature-resolved SANS in a wide q-range. The diblock copolymer has been investigated at a concentration of 50 g L−1 in D2O, both in saltfree solution and in 0.004 M NaBr solution. NaBr is chosen because it shows a stronger effect on the phase behavior than other salts.53 A relatively high polymer concentration is chosen to enhance the scattering intensity. The use of fully deuterated water, D2O, ensures maximum contrast between the polymer and the solvent. Figure 4 presents the SANS curves of the salt-free solution of PSPP430-b-PNIPAM200 in D2O during heating. The three regimes already distinguished by turbidimetry measurements are clearly discernible by the curve shapes. For PSPP430-bPNIPAM200, the SANS curve in regime I (blue squares) features a smooth decay starting at the lowest q values with a shallow maximum at 0.16 nm−1 and becomes flat above ca. 3 nm−1. The curves in regime II (green up and down triangles) rise slightly up to ca. 0.16 nm−1, then decay smoothly, and become flat at ca. 3 nm−1. The curves in regime III (red left and right triangles) decay steeply with a shallow second maximum at ca. 0.15 nm−1, before leveling off at ca. 3 nm−1. The changes in the curves are observed at the values of CPUCST and CPLCST obtained using turbidimetry (Figure 3b). To analyze the structures, model fits are carried out. Figure 5 shows four examples of the best fits to the scattering curves of the PSPP430-b-PNIPAM200 solution using the model described in the Methods section (eqs 2 and 7). The fits, which show good agreement with the data in all regimes, reveal substantial structural changes when CPUCST and CPLCST are crossed. The results of the fits using eq 2, applied in regimes I and II, are summarized in Table 2. The results from fitting eq 7, applied in regimes I (as an alternative) and III, are compiled in Table 3 and in Figure 6. According to the scenario described above (Figure 2), molecularly dissolved polymers are expected in the diblock copolymer solution in regime II. For unimers in dilute solution,

point CPLCST of PNIPAM in D2O is known from literature to be about 32 °C.47,48 Accordingly, the gap between the UCST and the LCST transition in the diblock copolymer is expected to be small, as intended. Figure 3a shows a representative light transmission curve of PSPP430-b-PNIPAM200 in D2O at 10 g L−1. Prior to the

Figure 3. (a) Light transmission curve of a 10 g L−1 solution of PSPP430-b-PNIPAM200 in salt-free D2O. The red dashed and blue dash-dotted lines indicate the UCST and LCST values, respectively. (b) Concentration dependence of the cloud points of PSPP430-bPNIPAM200 in salt-free D2O (closed symbols) and in 0.004 M NaBr (open symbols). Red spheres and blue squares represent the UCST and LCST values, respectively. The dashed lines are guides to the eye. The black up and down triangles mark the cloud points of a 50 g L−1 solution of PSPP430 and the literature value of PNIPAM47,48 in salt-free D2O, respectively.

measurements, the sample was equilibrated at 25 °C for 2−3 h. The measurements have been performed during heating and cooling runs from 25 °C to 50 °C and from 25 °C to 5 °C, as described in the Methods section. Figure 3b shows the concentration dependence of the resulting cloud points in salt-free D2O and in 0.004 M NaBr solution in D2O. Three regimes are distinguished in the transmission curve (Figure 3a) indicated as I, II, and III. In regimes I and III, the solution is turbid. However, in regime III, some light is still transmitted, while in regime I, the transmission of light is blocked. Moreover, the increase in turbidity at CPUCST is abrupt, whereas in regime III, the transmission decreases more gradually with increasing temperature. This difference suggests the presence of different self-assembled structures in regimes I and III. Remarkably, in the entire temperature range studied, the maximum transmission is significantly lower than 100%, even in regime II, where both blocks are expected to be in a molecularly dissolved state. When comparing the cloud points of the 50 g L−1 solutions of the homopolymers PSPP430 and PNIPAM with the ones of the diblock copolymer PSPP430-b-PNIPAM200, interesting differences are revealed. The CPUCST of the diblock copolymer is 21.2 ± 0.5 °C, thus about 8 K lower than the one of the homopolymer PSPP430 solution; this is a marked reduction. The CPLCST value of the diblock copolymer is 32.3 ± 0.5 °C, i.e., equal to the CPLCST of the PNIPAM homopolymer. Thus, F


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Figure 4. SANS curves from a 50 g L−1 salt-free solution of PSPP430-bPNIPAM200 in D2O (symbols), where only every third data point is shown for clarity, together with the model fits (black lines) (a). In (b), the curves are shifted in intensity by factors of 80 with respect to each other for better visibility. Regimes I, II, and III are indicated by the blue, green, and red color, respectively.

single chain scattering, described by the Debye form factor, would be expected or, for more concentrated solutions, scattering of the Ornstein−Zernike type. However, as tested by fitting these models to the curves, none of these behaviors are observed in the experiments. Instead, the SANS curves display a peak at a rather high q value, which is typical of polyelectrolytes in salt-free solution.82 In these systems, the spatial distribution of the chains results in a characteristic correlation peak with a maximum at q0, corresponding to an average distance d0 = 2π/q0 between the scattering objects (such as spherical particles) or between charged domains.83,84 Thus, we analyze the SANS curves in regime II using the model described in eq 2, where the solvation term (eqs 4−6) is used to describe the correlation peak and scattering at high q values, whereas the Porod term (eq 3) is not needed since no forward scattering is observed (Figure 5c). The solvation term reveals that the correlation length, ξ, which can be regarded as the distance between the neighboring entanglement points, decreases from 6.5 ± 0.2 nm at 22 °C to 6.0 ± 0.1 nm at 29 °C (Table 2). This decrease of the correlation length may be due to the different properties of the two blocks: polymer− polymer intermolecular interactions dominate over the interactions with water molecules for the PSPP block at 22 °C, which is very close to its CPUCST, whereas for the PNIPAM block, both types of interactions are equal in strength, and PNIPAM may form a hydrophilic shell around PSPP, which is at the origin of the higher ξ value. In contrast, at 29 °C, both blocks are in theta solvent conditions, and ξ reflects the molecular conformation of the entire polymer. The solvation Porod exponent, m, is 2.00 ± 0.03 and 1.93 ± 0.02 at 22 and 29 °C, respectively, indicating that the system is close to theta solvent conditions with the higher value at 22 °C again being

Figure 5. Representative SANS curves from a 50 g L−1 PSPP430-bPNIPAM200 solution in D2O, where only every third data point is shown for clarity, together with the model fits (black full lines). The symbols show the experimental data at 15 °C (regime I, a, b), 29 °C (regime II, c), and 49 °C (regime III, d). The other lines represent the contributions to the models as described in the graphs.

Table 2. Best Fit Parameters of Eq 2 for the SANS Data of a 50 g L−1 PSPP430-b-PNIPAM200 Solution in D2O in Regimes I and II regime I

regime II

15 °C IP α C ξ [nm] m d0 [nm]

22 °C

29 °C

4.2 ± 0.1 6.5 ± 0.2 2.00 ± 0.03 52 ± 3

3.5 ± 0.1 6.0 ± 0.1 1.93 ± 0.02 50 ± 3

−10

(3.2 ± 0.1) × 10 4.1 ± 0.1 5.8 ± 0.1 8.6 ± 0.2 1.94 ± 0.03 48 ± 2

related to the shell. The scaling factor of the solvation term, C, decreases from 4.2 ± 0.1 at 22 °C to 3.5 ± 0.1 at 29 °C. As expected, the value increases as CPUCST is approached. The G


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Table 3. Best Fit Parameters of Eq 7 for the SANS Data of a 50 g L−1 PSPP430-b-PNIPAM200 Solution in D2O in Regimes I and III regime I

regime III

15 °C ravg [nm] P rmic [nm] rcore [nm] pcore RHS [nm] η IP α IOZ ξ [nm] SLD sphere/core [nm−2] SLD shell [nm−2]

39 °C

49 °C

4.4 ± 0.1 0.48 ± 0.03

18 ± 2 0.12 ± 0.01 (1.5 ± 0.5) × 10−10 4.1 ± 0.2 1.9 ± 0.2 4.0 ± 0.3 (8.0 ± 0.3) × 10−5

86 ± 4 67 ± 4 0.26 ± 0.02 52 ± 3 0.17 ± 0.02

92 ± 4 73 ± 4 0.26 ± 0.03 54 ± 3 0.17 ± 0.01

8.6 ± 0.7 7.9 ± 0.9 (8.0 ± 0.3) × 10−5 (3.7 ± 0.2) × 10−4

6.2 ± 0.5 6.7 ± 0.5 (8.1 ± 0.2) × 10−5 (4.8 ± 0.2) × 10−4

terms are needed, including the Porod term to describe the scattering at low q values (Figure 5a). The solvation term reveals the correlation length ξ = 8.6 ± 0.3 nm (Table 2). Analogous to the correlation length in regime II at 22 °C, it describes the correlation in the hydrophilic PNIPAM shell, surrounding the collapsed PSPP in the core, and it is larger than at higher temperatures. The solvation Porod exponent is m = 1.94 ± 0.03, indicating that the solvent is still close to a theta solvent for the PNIPAM block. The scaling factor is C = 5.8 ± 0.1, which is 1.4−1.7 times higher than in regime II, which is an indication of the onset of phase separation.72 d0 is 48 nm, i.e., similar to the values obtained in regime II. The size of the large aggregates cannot be resolved by the SANS instrument, but the upturn of the intensity at q values below 0.08 nm−1 can be approximated by the Porod law, IP(q) (eq 3). The Porod exponent is α = 4.1 ± 0.1, which indicates the presence of compact aggregates with smooth surfaces. According to the scenario for the system depicted in Figure 2, in regime I, micelle formation is expected at temperatures below the CPUCST. Therefore, the curve in regime I (at 15 °C) has been additionally fitted using the model described in eq 7, based on spheres (eqs 8−10) correlated by a hard-sphere structure factor (eqs 13−15), plus an Ornstein−Zernike term (eq 16) describing the concentration fluctuations in the noncompact shell and Porod scattering due to very large aggregates (Figure 4b). The fitting curve fits the data equally well and allows gaining additional structural information. The polydisperse spherical particles at 15 °C have an average sphere radius ravg = 4.4 ± 0.1 nm with a polydispersity p = 0.48 ± 0.03 (the polydispersity can be enhanced due to aggregation) (Table 3 and Figure 6). The hard-sphere radius (or half the interparticle distance) is RHS = 18 ± 2 nm, which is slightly smaller than d0/2 = 24 nm obtained by the solvation model. The decay of the scattering intensity at high q values is described by the Ornstein−Zernike (OZ) structure factor, which reveals ξ = 4.0 ± 0.3 nm, which is half the value from the solvation model and may comprise both the inner part and the shell of the particles. The SLD value of the spherical particles was fixed in the range (0.79−0.82) × 10−4 nm−2, which corresponds to the range of SLD values of the PSPP and PNIPAM blocks. The forward scattering at low q values is again described by the Porod law with an exponent α = 4.1 ± 0.2, which confirms the presence of compact aggregates with smooth surfaces. Altogether, in regime I, small spheres seem to

Figure 6. Results from fitting of the model in eq 7 to the SANS curves in regimes I and III (Figure 4). Temperature dependence of (a) the micellar radius, ravg (closed squares), the micellar radius of the core− shell structure, rmic (closed triangles up), and the core radius, rcore (closed triangles down), the hard-sphere radius, RHS (open spheres); (b) the correlation length, ξ (closed diamonds), (c) the volume fraction, η (closed spheres), and (d) the SLD values of the polymer spheres (stars) and the core (closed triangles left) and the shell (closed triangles right) of the core−shell micelles. In (a) and (b), a logarithmic axis is used. In some cases, the symbol size is larger than the error bar. Red dashed and blue dash-dotted lines represent the CPUCST and CPLCST values from turbidimetry. Regimes I, II, and III are indicated on top of the graph.

average distance between the charged domains, d0, is 52 ± 3 and 50 ± 3 nm at 22 and 29 °C, respectively. At this large length scale the system is rather unaffected by the proximity of CPUCST. The heterogeneities observed in regime II are the origin of the reduced transmission (significantly below 100%) in this regime (Figure 3a). The shape of the curve in regime I at high q values is similar to those in regime II (Figure 4), but the overall scattering intensity is higher, which may be due to a higher contrast, due to aggregation. At low q values, the scattering curve indeed differs strongly: The increased forward scattering confirms the assumption of the presence of large aggregates. The curve in regime I can be fitted using the same model eq 2. This time, all H


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solubility of the PSPP block is driven by the electrostatic interactions between water and the charged polymer chains. In regimes I and III, the diblock copolymer is amphiphilic, but with reversed hydrophilic and hydrophobic blocks, and forms micelles, presumably of the core−shell type. In regime I, the PSPP coils overlap with each other, thus mimicking the molecularly crowded environment, and the solubility is driven by the PNIPAM block. The spherical particles detected in regime I are comparably small with radii of about 5 nm but form very large aggregates as well. The core−shell structure of the micelles expected in regime I could not be resolved. This may be due to the aggregation governed by electrostatic interactions in the PSPP block together with the relatively short PNIPAM block. An alternative reason might be that the PSPP and PNIPAM blocks interact with each other, rather forming homogeneous micelle-like associates than distinct core−shell micelles. In contrast to regime III, at the LCST transition of the PNIPAM block, the particle radius increases abruptly to values of about 90 nm, and a core−shell structure is evident. No aggregation was observed, which may be hindered by the thick hydrophilic PSPP shell, creating a steric hindrance for the further aggregation and keeping the system in the solvated state. The self-assembly behavior was confirmed in temperatureresolved DLS experiments in backscattering geometry on the 10 g L−1 diblock copolymer solution in D2O (for experimental details and results see the Supporting Information). In good agreement with turbidimetric and SANS measurements, DLS reveals very large aggregates (Rh > 1000 nm) in regime I, unimers with Rh < 10 nm in regime II, and aggregates having radii of ca. 130 nm in regime III. Electrolyte Effect. Turbidimetry revealed changes of the cloud points of the diblock copolymer in D2O upon addition of NaBr (Figure 3). In a 50 g L−1 solution of PSPP430-bPNIPAM200 in 0.004 M NaBr in D2O, the CPUCST is found to increase by about 0.6 K compared to the one in salt-free D2O. To gain information about the structural changes caused by electrolyte addition, temperature-dependent SANS measurements of a 50 g L−1 solution of PSPP430-b-PNIPAM200 in 0.004 M NaBr in D2O have been performed (Figure 8). The SANS curves of PSPP430-b-PNIPAM200 in 0.004 M NaBr in D2O show a significantly increased forward scattering at q values below ca. 0.07 nm−1 in regime I (Figure 8b) and weakly increased forward scattering in regime II below ca. 0.16 nm−1 (Figure 8c). Above these q values, the curves stay virtually unchanged compared to the ones in salt-free D2O. The shape of the curves in regime III (red) remains unchanged over the entire q range, and only at q values below 0.03 nm−1, the intensity is 1.5 times lower compared to the one in salt-free solution (Figure 8c). The same fitting models are used for the curves with and without salt, and the resulting parameters are compiled in Table 4 (using eq 2) and in Table 5 and Figure 8 (using eq 7). In regime II, again none of the models describing single chain scattering fit the curves, and the model described in eq 2 is applied. The solvation term reveals that the correlation length changes from 8.3 ± 0.3 nm at 22 °C to 6.5 ± 0.2 nm at 29 °C. Similarly to the observation in salt-free conditions at 22 °C, ξ describes the correlations in the hydrophilic shell, and its decrease at 29 °C indicates weakening of the repulsive interactions. The solvation Porod exponent, m, is around 2.0, indicating good solvent quality. The scaling factor C decreases from 7.7 ± 0.2 at 22 °C to 5.5 ± 0.1 at 29 °C, indicating the

form with a highly polydisperse radius and an inner correlation length of a few nanometers. These spheres are correlated; moreover, they form large aggregates. The correlation peak characteristic of the polyelectrolyte systems, which is clearly seen in the scattering curves in regimes I and II, it is not evident in regime III, i.e., at temperatures far above the CPUCST (Figure 4). In regime III, the curves cannot be fitted using the same model (eq 2) because additional scattering is observed in a large q range (up to 0.1 nm−1), which points to self-assembly of the diblock copolymers on length scales not much higher than the mesh size of the polymer solution. The model described in eq 7 is more applicable in regime III, where the form factor for core−shell spheres (eqs 11 and 12) together with the hard-sphere and the Ornstein− Zernike structure factors were used, while the Porod term was not needed (Figure 5d). Thus, in regime III, spherical core− shell particles with a polydisperse core are formed. The average core radius is 67 ± 4 and 73 ± 4 nm at 39 and 49 °C, respectively, with a moderate polydispersity p = 0.26 ± 0.03 and the shell thickness t = 19 ± 1 nm (Table 3). Thus, the micellar radii are rmic = 86 ± 4 nm at 39 °C and 92 ± 4 nm at 49 °C. The hard-sphere structure factor reveals the correlation between the micelles whose distance 2RHS is 104 ± 6 nm at 39 °C and 108 ± 6 nm at 49 °C. The hard-sphere volume fraction of correlated micelles, η, is slightly higher than the one in regime I, namely about 0.17. RHS is smaller than the micelle radius but follows the same trend. This may be attributed to different species being present at the micellar surface in regimes I and III. The PSPP block is about 3 times longer than PNIPAM block, and in regime III, the strong attractive interactions in the PNIPAM block lead to the formation of a hydrophobic core and allow interpenetration of the hydrophilic PSPP shells. The SLD value of the core varies in the range of (0.79−0.82) × 10−4 nm−2, which is again comparable to the values of PSPP and PNIPAM, whereas the SLD of the shell is in the range (3.7−4.8) × 10−4 nm−2, indicating a high amount of D2O in the hydrophilic shell of the micelles, namely 54−74% of D2O. The correlation length ξ in regime III is 7.9 ± 0.7 nm at 39 °C and 6.7 ± 0.5 nm at 49 °C, thus slightly higher than in regimes I and II. In regime III, ξ describes the correlation in the hydrophilic PSPP shell. The slight increase of ξ at CPLCST indicates a decrease of the osmotic compressibility and hence the shrinkage of the core due to the reinforced repulsive interaction in the PSPP shell. No forward scattering is observed in the SANS curves in regime III, which is in agreement with the results from turbidimetry; namely, the solution is not completely turbid. The structures in the three regimes, according to SANS and expectations relating to the (aggregated) behavior, are depicted in Figure 7. In regime II, both of the blocks are soluble; the

Figure 7. Schematic representation of the micelles/polymer coils in the three regimes as indicated. Red: PSPP block; blue: PNIPAM block. I


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the electrostatic screening. In contrast to the salt-free polymer solution, the Porod law has to be applied at 22 °C to describe the increased forward scattering. The Porod exponent α = 3.1 ± 0.1 indicates the presence of aggregates with rough surfaces. The Porod amplitude is more than 10 times lower than in regime I, meaning that only few aggregates are formed. Since the solution starts to phase separate at 22 °C, the SANS model described in eq 7 can be applied as well. The fitting results (Table 5) are compared to the ones obtained in salt-free solution at 15 °C, i.e., in regime I. The spherical particles about 1.2 nm smaller in radii and have a higher polydispersity p = 0.64 ± 0.07. The other parameters reveal no or only minor changes. The Porod law has to be applied to describe increased forward scattering, and it reveals the same parameters as when using the solvation model (eq 2). The curve in regime I can also be fitted using the two models described in eqs 2 and 7. Comparison of the resulting fitting parameters in regime I using eq 2, with and without NaBr addition, reveals the following changes: With NaBr, the solvation term displays a slightly increased ξ value (on average about 0.4 nm higher). The solvation Porod exponent, m, is 1.86, indicating a decline of the solvent quality. The scaling factor is lower (C = 4.8 ± 0.1), which is consistent with the shift of the phase separation to regime II to a higher temperature. d0 is about 3 nm higher. The Porod exponent, α, is 4.3 ± 0.1 with its amplitude being about 2 times higher than the one in salt-free solution. Comparison of the resulting fitting parameters in regime I with and without NaBr addition when using eq 7 reveals the following changes: ravg is only 0.2 nm higher with a similar polydispersity, p = 0.45 ± 0.04. 2RHS is 4 nm lower, indicating more closely spaced spheres, but which have a lower volume fraction η = 0.09 ± 0.1. The correlation length ξ is unchanged. The Porod law reveals α = 4.4 ± 0.2 with the amplitude being about 4 times higher than the one in salt-free solution, indicating stronger aggregation, possibly due to the screening effect. The SLD values are again unchanged. In regime III, the core−shell micelles are smaller than in saltfree solution and characterized by a more stable size within this temperature range: rcore = 58 ± 3 nm, and the core polydispersity stays unchanged within the error, p = 0.28 ± 0.03, the shell thickness is t = 20 ± 1 nm, and thus rmic = 79 ± 4 nm. The micelles are correlated as well, 2RHS is 100 ± 10 nm, and the volume fraction is about 0.19. Thus, the interparticle interactions are stronger, and the core−shell micelles are smaller in the presence of electrolyte. The SLD value of the core stays in the range of (0.79−0.82) × 10−4 nm−2, whereas the SLD of the shell is in the range (3.8−4.0) × 10−4 nm−2, indicating 55−59% of D2O, which is less compared to the saltfree conditions. The correlation length ξ in regime III is 8.8 ± 0.3 nm at 39 °C and 8.2 ± 0.4 nm at 49 °C, thus comparably higher than in salt-free conditions. In this regime, ξ describes the correlation in the hydrophilic PSPP shell and may be increased because of the screening effect. Again, no forward scattering is observed. Thus, at low salt concentrations and in the region where the aggregation is induced by the thermoresponsive block, salt addition causes a reduction of the micellar size due to the shrinkage of the hydrophilic PSPP shell which contains charges. One would expect the polyelectrolyte peak to disappear in regime II upon addition of NaBr, due to the screening of the charges, and behavior similar to the one of a neutral polymer solution. The concentration of NaBr, 0.004 M, is too low and the general behavior of the polymer stays unchanged, and only

Figure 8. (a) SANS curves from 50 g L−1 solutions of PSPP430-bPNIPAM200 in salt-free D2O (open symbols, from Figure 4) and in 0.004 M NaBr in D2O (closed symbols), where only every third point is shown for clarity, together with the fitting curves (black lines). The curves are shifted in intensity as in Figure 4. Zooms of the low q region: curves in regime I at 15 °C (b), in regime II at 22 °C (c), and in regime III at 49 °C (d), where every second point is shown for clarity.

Table 4. Best Fit Parameters of Eq 2 to the SANS Data of a 50 g L−1 PSPP430-b-PNIPAM200 Solution in 0.004 M NaBr in D2O in Regimes I and II regime I IP α C ξ [nm] m d0 [nm]

regime II

15 °C

22 °C

15 °C

(7.4 ± 0.3) × 10−10 4.3 ± 0.1 4.8 ± 0.1 8.2 ± 0.3 1.86 ± 0.03 51 ± 3

(2.1 ± 0.1) × 10−8 3.1 ± 0.1 7.7 ± 0.2 8.3 ± 0.3 1.95 ± 0.04 55 ± 3

5.5 ± 0.1 6.5 ± 0.2 2.00 ± 0.03 59 ± 4

onset of phase separation at 22 °C, which is shifted to a higher temperature than in salt-free D2O due to the presence of NaBr. The average distance between the charged domains, d0, is 55 ± 3 nm at 22 °C and 59 ± 4 nm at 29 °C, i.e., on average about 6 nm higher than in salt-free polymer solution, which is due to J


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Table 5. Best Fit Parameters of Eq 7 for the SANS Data of a 50 g L−1 PSPP430-b-PNIPAM200 Solution in 0.004 M NaBr in D2O in Regimes I and III regime I

regime II

regime III

regime III

22 °C

39 °C

49 °C

15 °C ravg [nm] P rmic [nm] rcore [nm] pcore RHS [nm] η IP α IOZ ξ [nm] SLD sphere/core [nm−2] SLD shell [nm−2]

4.6 ± 0.1 0.45 ± 0.04

16 ± 2 0.09 ± 0.01 (6.0 ± 0.3) × 10−10 4.4 ± 0.2 1.9 ± 0.2 4.0 ± 0.4 (8.0 ± 0.3) × 10−5

3.3 ± 0.1 0.64 ± 0.07

18 ± 2 0.12 ± 0.02 (2.1 ± 0.2) × 10−8 3.1 ± 0.3 3.0 ± 0.4 4.5 ± 0.4 (8.0 ± 0.4) × 10−5

■

78 ± 3 58 ± 3 0.28 ± 0.02 49 ± 3 0.19 ± 0.03

79 ± 4 60 ± 3 0.28 ± 0.03 51 ± 3 0.18 ± 0.03

12.6 ± 1.1 8.8 ± 0.3 (8.0 ± 0.3) × 10−5 (3.8 ± 0.2) × 10−4

11.5 ± 0.9 8.2 ± 0.4 (8.0 ± 0.4) × 10−5 (4.0 ± 0.2) × 10−4

DISCUSSION We have studied the aggregation behavior of a diblock copolymer consisting of a zwitterionic PSPP block and a nonionic PNIPAM block in D2O, exhibiting both UCST and LCST behavior, respectively. PSPP430-b-PNIPAM200 has been found to feature solubility and double thermoresponsiveness in D2O in the temperature range studied, namely 10−65 °C. Since the UCST of PSPP is lower than the LCST of PNIPAM, both blocks are hydrophilic at intermediate temperatures. The aggregation behavior responds to two stimuli: temperature and, due to the zwitterionic PSPP block, electrolyte concentration. By means of turbidimetry, we elucidated the dependence of the cloud points (CPUCST and CPLCST) solutions of PSPP430-bPNIPAM200 in D2O having concentrations of 10−50 g L−1. The value of CPUCST of the diblock copolymer is decreased compared to the one of a PSPP homopolymer with identical molar mass; i.e., it is altered by the presence of the PNIPAM block. The polymer architecture and particularly the presence of charges in the PSPP block affect the conformation of the diblock copolymer in solution. In good agreement with turbidimetric measurements, temperature-resolved SANS measurements reveal three different regimes in dependence on temperature. Below the LCST-type transition of the PNIPAM block, SANS shows the existence of a well-pronounced broad polyelectrolyte peak in the scattering functions. Because of the properties of the zwitterionic PSPP block, the PSPP430-bPNIPAM200 diblock copolymer in aqueous solution exhibits behavior similar to polyelectrolytes. The electrostatic interactions between the PSPP chains were accounted for by using a model comprising terms for solvation and aggregation, which contain information about the density and composition fluctuations, respectively. Thus, in regime II between the UCST- and LCST-type transitions, although appearing visually clear, SANS reveals that the polymer chains have expanded conformations in solution, where the solvent conditions are good for both blocks. In regime I below the UCST-type transition, SANS reveals phase separation and formation of very large aggregates with a smooth surface, which causes turbidity. Using another fitting model in regime I, describing correlated spheres, small homogeneous spherical particles having a radius of about 5 nm were found, which are correlated and form very large aggregates, as mentioned above. In contrast, in regime III

Figure 9. Results from model fitting to the SANS curves in Figures 5 and 8 from PSPP430-b-PNIPAM200 in salt-free D2O (black symbols) and in 0.004 M NaBr in D2O (red symbols), respectively. Same designations as in Figure 5. The red dashed and the vine dotted lines represent CPUCST in in salt-free D2O and in 0.004 M NaBr in D2O, respectively, and the blue line represents the (unchanged) CPLCST value, all determined by turbidimetry.

a shift of the CPUCST to higher values is observed. The fact that the Porod law applies in regime I and in regime II at 22 °C together with the increase of the solvation scaling factor indicates the shift of the onset of the phase separation to higher temperatures. A small amount of electrolyte causes an increase of the attractive interactions between the polymers and hence an increase of the distance between charged domains, a slight increase of the size of the spherical micelles below the CPUCST, and an enhanced aggregation. The core−shell micelles formed in regime III become more compact in the presence of electrolyte, which is due to the screening effect. The decrease of the SLD value in regime III indicates a lower content of D2O in the micellar shell. Thus, minor structural changes are found in all regimes for PSPP430-b-PNIPAM200 solutions in D2O upon the addition of NaBr at a concentration 0.004 M. We attribute these to the ionic strength sensitivity of PSPP. K


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above the LCST-type transition, the partially turbid solution features spherical core−shell micelles, having a polydisperse core and a radius of about 90 nm; i.e., they are significantly larger than below the UCST-type transition, but these micelles do not form large aggregates. The marked differences of the aggregation in regimes I and III may be partly due to the difference in block lengths, the PSPP block being twice as large as the PNIPAM block, and partly due to their individual properties, such as e.g. dominating electrostatic interactions versus hydrogen bonding with water. Dynamic light scattering in backscattering geometry confirmed the overall behavior. The electrolyte effect on the aggregation behavior of the diblock copolymer solution in D2O is investigated by means of turbidimetry and SANS. The CPUCST has previously been found to increase at salt concentrations up to 0.005 M,53 in contrast to CPLCST, which remains virtually unchanged. SANS reveals slight structural changes in all regimes: enhanced aggregation and increase of the small spheres radius in regime I, an increase of the distance between the charged domains in regime II, and a decrease of the micellar dimensions in regime III, caused by the screening electrostatic effect. The salt concentration (0.004 M NaBr) is too low to alter the general behavior of the polymer. Salt-induced structural changes of PSPP430-b-PNIPAM200 in solution during heating may be assigned to the sensitivity of the PSPP block to ionic strength, as expected. To conclude, the diblock copolymer PSPP430-b-PNIPAM200 has interesting double thermoresponsive properties and is water-soluble in a broad temperature range. It exhibits schizophrenic aggregation behavior with phase transitions from one self-assembled structure to another self-assembled structure through an intermediate, nearly molecularly dissolved state. The UCST-type transition can easily be tuned by changing the diblock copolymer architecture, namely by varying the block length ratio and by adding electrolyte. The tunable thermoresponsive properties of these block copolymers make them promising candidates for a variety of applications, e.g., in the biomedical field and in the development of switchable surfaces and thermo-optical devices.43

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REFERENCES

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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.6b01186. Dynamic light scattering: description of the experimental details; results (PDF)

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Article

AUTHOR INFORMATION

Corresponding Authors

*E-mail [email protected], Ph +49 331 997 5225, Fax +49 331 997 5036 (A.L.). *E-mail [email protected], Ph +49 89 289 12 447, Fax +49 89 289 12 473 (C.M.P.). Funding

We thank Deutsche Forschungsgemeinschaft (DFG) for financial support (Pa771/14-1, Mu1487/17-1, La611/11-1). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Institut Laue-Langevin is acknowledged for beam time allocation and for providing excellent equipment. L


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Aggregation Behavior of Doubly Thermoresponsive Polysulfobetaine

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