Dual Orthogonal Switching of the âSchizophrenic ... - ACS Publications

Article Cite This: Macromolecules XXXX, XXX, XXX−XXX

Dual Orthogonal Switching of the “Schizophrenic” Self-Assembly of Diblock Copolymers Natalya S. Vishnevetskaya,† Viet Hildebrand,‡ Margarita A. Dyakonova,† Bart-Jan Niebuur,† Konstantinos Kyriakos,† Konstantinos N. Raftopoulos,† Zhenyu Di,§ Peter Müller-Buschbaum,† André Laschewsky,*,‡,∥ 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 § Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science (JCNS) at MLZ, Lichtenbergstr. 1, 85747 Garching, Germany ∥ Fraunhofer Institut für Angewandte Polymerforschung, Geiselbergstr. 69, 14476 Potsdam-Golm, Germany S Supporting Information *

ABSTRACT: Based on diblock copolymers, a pair of “schizophrenic” micellar systems is designed by combining a nonionic and thermoresponsive block with a zwitterionic block, which is thermoresponsive and salt-sensitive. The nonionic block is poly(N-isopropylacrylamide) (PNIPAM) or poly(N-isopropylmethacrylamide) (PNIPMAM) and exhibits a lower critical solution temperature (LCST) behavior in aqueous solution. The zwitterionic block is a polysulfobetaine, i.e., poly(4-((3-methacrylamidopropyl)dimethylammonio)butane-1-sulfonate) (PSBP), and has an upper critical solution temperature (UCST) behavior with the clearing point decreasing with increasing salt concentration. The PSBP-b-PNIPAM and PSBP-b-PNIPMAM diblock copolymers are prepared by successive reversible addition−fragmentation chain transfer (RAFT) polymerizations. The PSBP block is chosen such that the clearing point of the homopolymer is significantly higher in pure water than the cloud point of PNIPAM or PNIPMAM. Using turbidimetry, 1H NMR, and small-angle neutron scattering, we investigate the overall phase behavior as well as the structure and interaction between the micelles and the intermediate phase, both in salt-free D2O and in 0.004 M NaBr in D2O in a wide temperature range. We find that PSBP-b-PNIPAM at 50 g L−1 in salt-free D2O is turbid in the entire temperature range. It forms spherical micelles below the cloud point of PNIPAM and cylindrical micelles above. Similar behavior is observed for PSBP-b-PNIPMAM at 50 g L−1 in salt-free D2O with a slight and smooth increase of the light transmission below the cloud point of PNIPMAM and an abrupt decrease above. Upon addition of 0.004 M NaBr, the UCSTtype cloud point of the PSBP-block is notably decreased, and an intermediate regime is encountered below the cloud point of PNIPMAM, where the light transmission is slightly enhanced. In this regime, the polymer solution exhibits behavior typical for polyelectrolyte solutions. Thus, double thermosensitive and salt-sensitive behavior with “schizophrenic” micelle formation is found, and the width of the intermediate regime, where both blocks are hydrophilic, can be tuned by the addition of electrolyte.

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INTRODUCTION Micelle formation by amphiphilic diblock copolymers in selective solvents has been amply investigated.1−4 Proposed applications of amphiphilic diblock copolymers include the encapsulation, transport, and release of hydrophobic substances.4,5 In particular, diblock copolymers featuring two thermoresponsive blocks offer more possibilities to fulfill these tasks,6−8 especially if a block with upper critical solution temperature (UCST) behavior is combined with a block with lower critical solution temperature (LCST) behavior. Such diblock copolymers are expected to be able to form core−shell micelles of both types, and these structures may be switched by a change in temperature, thereby causing a so-called “schizophrenic self-assembly” which is gaining increasing interest.8−17 The transition between these types of micelles © XXXX American Chemical Society

may proceed via a molecularly dissolved phase or via precipitation, depending on the relative positions of the UCST and the LCST type transition.18 Poly(N-isopropylacrylamide) (PNIPAM, Figure 1a) and, to a lesser degree, poly(N-isopropylmethacrylamide) (PNIPMAM, Figure 1b) have been frequently used as LCST block in thermoresponsive block copolymers. PNIPAM and PNIPMAM have cloud points, CPLCST, at ca. 32 °C19,20 and 44 °C,21−23 respectively, in aqueous solution. Among the potential UCST blocks, polyzwitterions featuring sulfobetaine moieties have attracted interest since they have the additional advantage of Received: January 15, 2018 Revised: March 9, 2018

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DOI: 10.1021/acs.macromol.8b00096 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

Figure 1. Chemical structures of the LCST and UCST polymers used to create schizophrenic diblock copolymers: (a) PNIPAM, (b) PNIPMAM, (c) PSPP, and (d) PSBP.

being highly biocompatible.24,25 CPUCST of polysulfobetaines depends strongly on molar mass. Furthermore, higher values are reported for D2O as compared to H2O.26−28 Moreover, their CPUCST is sensitive to the type and concentration of added low molar mass salts in a nonlinear and complex fashion.26−31 The hitherto for “schizophrenic” thermoresponsive systems mostly employed polysulfobetaine poly(N,N-dimethyl-N-(3(methacrylamido)propyl)ammoniopropanesulfonate) (PSPP, Figure 1c)10,11,17,32−34 features UCST behavior with a clearing point, CPUCST, which is lower than CPLCST of PNIPAM and PNIPMAM.26 In our previous work, we investigated PSPP432-bPNIPAM200 and PSPP498-b-PNIPMAM144 diblock copolymers in dilute aqueous solution, using turbidimetry, dynamic light scattering, and small-angle neutron scattering (SANS).32,33 For PSPP432-b-PNIPAM200, we observed three regimes in dependence on temperature in salt-free conditions (Figure 2a): In

amount of salt (0.004 M NaBr) resulted only in slight structural changes in all regimes, presumably because the salt concentration was very low. In the present work, we extend our studies on “schizophrenic” block copolymers by designing systems that aim at a richer phase behavior, as sketched in Figure 2b. In addition to the regimes I−III described above, it features also the state where both blocks are water-insoluble, named regime II′. Thus, it could represent a more versatile system because switching between the inverted amphiphilic states can proceed via aggregates or via molecularly dissolved copolymers. To achieve this goal, we replace the UCST block PSPP by another polysulfobetaine having a higher CP, namely, with poly(4-((3methacrylamidopropyl)dimethylammonio)butane-1-sulfonate) (PSBP, Figure 1d).27 In PSBP, the ammonium and the sulfonate groups are separated by a spacer which is longer by one methylene group as compared to PSPP. This molecular variation effectively raises the CPUCST of PSBP markedly above the one of PSPP.27 Moreover, the CPUCST of PSBP decreases monotonously with increasing salt (sodium halide) concentration;27 i.e., a general salting-in effect is observed, in contrast to the nonlinear behavior encountered for PSPP.26 Thus, to achieve the phase behavior sketched in Figure 2b, we combine PSBP with either PNIPAM or PNIPMAM, which both feature LCST behavior (Figure 3). Their coil-to-globule phase transition temperatures are only weakly sensitive to the addition of salts,35−38 different from the behavior of PSPP and PSBP. Note that, counterintuitively, the cloud point of PNIPAM is about 12 °C lower than the one of PNIPMAM,39,40 probably due to steric effects.41 We investigate comparatively aqueous solutions of the diblock copolymers PSBP80-bPNIPAM100 and PSBP80-b-PNIPMAM115, and also address the effect of NaBr on the phase behavior of the latter. Compared to the previously investigated diblock copolymers, PSPP432-b-PNIPAM200 and PSPP498-b-PNIPMAM144,32,33 the overall molar masses of the present, PSBP-based diblock copolymers are lower. In particular, the PSBP block is kept considerably smaller than the PSPP blocks used previously in order to adjust CPUCST below 100 °C.27 Consequently, the fractions of the zwitterionic PSBP blocks are lower than the ones of the PSPP blocks in our previous studies, which renders the diblock copolymers more symmetric; i.e., the lengths of the zwitterionic and the nonionic blocks are more similar. This design is expected to facilitate the formation of both micelles and reverse micelles and possibly to lead to anisotropic micelles. Finally, taking the strong salting-in effect for the homopolymer PSBP into account, we intend to realize orthogonal switching via the addition of low molar mass salt. To characterize the overall phase behavior, we use turbidimetry on aqueous solutions of the two diblock copolymers and relate them to the cloud/clearing points

Figure 2. Schematic phase diagrams of aqueous solutions of diblock copolymers from a zwitterionic block having UCST behavior (red) and a nonionic block having LCST behavior (blue). (a) Observed for PSPP432-b-PNIPAM200 and PSPP498-b-PNIPAM144.32,33 (b) Phase behavior envisaged with the PSBP-b-PNIPAM and PSBP-b-PNIPMAM systems. Red dashed line: CPUCST of the PSPB block; blue dashdotted line: CPLCST of the PNIPAM/PNIPMAM block.

regime I below the CPUCST of the PSPP block, small spherical micelles were present which were correlated with each other. These micelles were homogeneous and did not exhibit the expected core−shell structure, which may be due to attractive interactions between the PSPP and PNIPAM segments. In regime II, between the CPUCST of the PSPP block and the CPLCST of the PNIPAM block, molecularly dissolved polymers were encountered at intermediate temperatures. The solution structure resembled the one of polyelectrolyte solutions, which we attributed to the now water-soluble PSPP blocks. In regime III, above the CPLCST of the PNIPAM block, spherical core− shell micelles with a PNIPAM core and a PSPP shell were formed.32 A very similar behavior was found for PSPP498-bPNIPMAM144.33 In both systems, the addition of a small B


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Figure 3. Chemical structures of the diblock copolymers investigated: (a) PSBP80-b-PNIPAM100 and (b) PSBP80-b-PNIPMAM115. orange reaction mixture was polymerized at 75 °C for 90 h. The reaction was stopped by allowing air into the flask and cooling to ambient temperature. After withdrawing a small amount for the analysis of monomer conversion by 1H NMR, the reaction mixture was precipitated into diethyl ether (repeated thrice); the diblock copolymer PSBP80-b-PNIPMAM115 was isolated by filtration and dried under high vacuum. FT-IR (selected bands, cm−1): 3387 ν(NH), 2971 ν(N+−CH3), 2938 ν(CH2), 1633 ν(amide I), 1523 ν(amide II), 1197 νas(SO3−), 1037 νs(SO3−). UV−vis absorbance maxima: in trifluoroethanol (λmax = 263, 292, and 442 nm) and in water (λmax = 285 and 440 nm). Fluorescence emission maxima: in trifluoroethanol (λPL = 538 nm) and in water (λPL = 538 nm). PSBP80-b-PNIPAM100 was synthesized analogously, engaging PSBP80 (1.500 g, 6.1 × 10−5 mol), NIPAM (0.690 g, 6.1 × 10−3 mol), and V-501 (0.0034 g, 1.2 × 10−5 mol) and polymerizing at 75 °C for 5 h. The synthesis of reference PNIPMAM195 was described before (Mnapp = 32 kg mol−1 with a dispersity index Đ = 1.2 by SEC with respect to PMMA standards).33 Determination of Cloud Points. The cloud points of the diblock copolymers were determined using a Cary 50 UV−vis spectrometer (Varian Inc., Palo Alto, CA) equipped with a single cell Peltier thermostat. Quartz glass cells (Hellma Analytics) with a light path of 10 mm were used. Transmittance measurements were carried out at a wavelength of 500 nm. The measurements were carried out during heating from 35 to 65 °C and during cooling from 35 to 15 °C in steps of 0.5 °C with a thermal equilibration time of 5 min at each temperature. The data were normalized to the absorption of the solvent-filled cell. Sample Preparation for SANS. Diblock copolymer solutions were prepared in salt-free D2O or in 0.004 M NaBr in fresh D2O (Deutero GmbH, purity 99.98%). The polymer concentration was 50 g L−1. All solutions were equilibrated for about 2 days in a thermoshaker at 35 °C (PSBP80-b-PNIPAM100) or 40 °C (PSBP80-bPNIPMAM115), where the polymers are expected to be molecularly dissolved. Small-Angle Neutron Scattering (SANS). SANS measurements of PSBP80-b-PNIPAM100 and PSBP80-b-PNIPMAM115 were carried out at instrument KWS-1 of the JCNS outstation at the Maier-Leibnitz-

from the corresponding homopolymers. Moreover, we investigate the effect of 0.002 and 0.004 M NaBr. Detailed structural studies are carried out using SANS in dependence on temperature in salt-free D2O and, at the example of PSBP80-bPNIPMAM115, in the presence of 0.004 M NaBr in D2O. D2O is chosen to increase the scattering contrast between the polymer and the solvent in neutron scattering. This way, we construct the phase diagram and characterize the micelles formed in regimes I and III.

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EXPERIMENTAL SECTION

Synthesis. Monomers N-isopropylacrylamide (NIPAM, TCI, 98%) and N-isopropylmethacrylamide (NIPMAM, Sigma-Aldrich, 97%) were crystallized from hexane. The initiator 4,4′-azobis(4-cyanopentanoic acid) (V501, Wako) was crystallized from methanol. Trifluoroethanol (TFE, Roth, 99.8%), sodium chloride (ChemSolute, 99%), sodium bromide (Sigma-Aldrich, 99%), and deuterated water (D2O, Armar, 99.9 atom % D for synthesis and characterization during synthesis, Deutero GmbH, purity 99.98% for structural characterizations) were used as received. Water was purified by a Millipore Milli-Q Plus water purification system (resistivity 18 MΩ cm−1). The synthesis of macro-chain-transfer agent PSBP80 (number-average degree of polymerization DP n = 80 by end-group analysis, corresponding to a number-average molar mass Mn of 25 kg mol−1 and Mnapp = 29 kg mol−1 with a dispersity index Đ = 1.3 by SEC with respect to PMMA standards) by the RAFT method using the fluorophore-labeled 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 described in ref 27. Diblock copolymers PSBP80-b-PNIPMAM115 and PSBP80-b-PNIPAM100 were obtained by chain extension of PSBP80 with NIPMAM and NIPAM, respectively, in analogy to the synthesis of corresponding block copolymers using PSPP as macro-chain-transfer agent.32,33 In more detail, PSBP80 (1.500 g, 6.1 × 10−5 mol), NIPMAM (3.110 g, 2.4 × 10−2 mol), and V-501 (0.0034 g, 1.2 × 10−5 mol) were dissolved in TFE (8 mL), purged with N2 for 30 min, and sealed. Then, the yellowC


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Macromolecules Table 1. Molecular Characteristics of the Polymers Studied Mn [kg mol−1] polymer PSBP80-bPNIPAM100 PSBP80-bPNIPMAM115

conversion of NIPAM/ NIPMAM [%]a

theoretically expectedb

via 1H NMRc

by UV/vis end-group analysisd

Mnapp [kg mol−1] by SECe

dispersity Đ by SECe

100

36

38

32

57

1.5

29

39

36

32

70

1.3

a

Determined by 1H NMR analysis of the crude reaction mixtures. bCalculated from the molar ratio of the converted nonionic monomer and the engaged PSBP macro-chain-transfer agent, assuming no chain termination and no change of DPn of PSBP after chain extension. cBy comparing the integrals of signals of the PSBP block with integrals of the signals of the PNIPMAM or PNIPAM block, respectively, assuming that DPn of PSBP is unchanged after chain extension. dCalculated from the maximum absorbance in TFE, using the extinction coefficient εmax of 1.87 × 104 L mol−1 cm−1 determined for the naphthalimide label on the polysulfobetaine in TFE. eBy SEC in hexafluoroisopropanol/50 mM CF3COONa, apparent values according to calibration with poly(methyl methacrylate) standards. For SEC elugrams and IR spectra of the polymers, see Supporting Information, Figures S1 and S2. Zentrum (MLZ) in Garching, Germany.42 The neutron wavelength was λ = 0.45 nm with a spread of 10%. Using sample−detector distances of 1.5, 8.0, and 20.0 m, a q range of 0.03−4.7 nm−1 was covered. q = 4π sin(θ/2)/λ is the momentum transfer where θ is the scattering angle. Samples were mounted in quartz glass cells (Hellma Analytics) with a neutron path of 1 mm. Measuring times were 5 min at 1.5 m, 15 min at 8 m, and 30 min at 20 m. Boron carbide was used for measurement of the dark current, and poly(methyl methacrylate) for the detector sensitivity, and measurement of the dark current. The scattered intensity was azimuthally averaged and corrected for background scattering from the solvent-filled cell and parasitic scattering, taking the transmissions into account. All operations were carried out using the software QtiKWS provided by JCNS. The diblock copolymers PSBP80-b-PNIPAM100 and PSBP80-bPNIPMAM115 were measured in pure D2O and PSBP80-b-PNIPMAM115 additionally in 0.004 M NaBr in D2O. Heating scans were carried out from 10 or 20 °C to 50 or 60 °C in steps of 5 or 10 °C with thermal equilibration times of 15 min. Analysis of SANS Curves. The SANS curves were analyzed by model fitting. The data from both diblock copolymers in regimes I and III were modeled using the following function:

I(q) = I0P(q)S(q) + Iagg(q) + Ifluct(q) + Ibg

For the form factor, different expressions were found to be appropriate. For both diblock copolymers in regime I, the form factor of polydisperse, homogeneous spheres was used with a Schulz distribution of radii.49 It contains the average radius, rsph, and the polydispersity, psph, as well as the difference of the scattering length densities (SLD) of the sphere, ρsph, and the solvent, ρsolvent (values used see below). In regime III, the form factor of flexible cylinders with polydisperse radius was applied, the latter also following a Schulz distribution.50,51 This form factor features the cross-sectional radius, rcyl, and its polydispersity, pcyl, the contour length, L, the Kuhn length, b, as well as the difference of the scattering length densities (SLD) of the cylinder, ρcyl, and the solvent, ρsolvent. The scattering length densities (SLD) of PSBP, PNIPAM, PNIPMAM, and D2O were calculated at 7.3 × 10−5, 8.1 × 10−5, 6.8 × 10−5, and 6.3 × 10−4 nm−2, assuming mass densities of 1.0 g cm−3 for PSBP and 1.1 g cm−3 for PNIPAM and PNIPMAM. The SLD values of the spherical or cylindrical particles in regimes I and III were kept in the range (7.3− 8.1) × 10−5 nm−2 for PSBP80-b-PNIPAM100 and (6.8−7.3) × 10−5 nm−2 for PSBP80-b-PNIPMAM115. For the solutions of PSBP80-b-PNIPMAM115 in 0.004 M NaBr in regime II, the curves were modeled by I(q) = Iagg(q) + Isolv(q) + Ibg

(1)

(2)

In all cases, the background was fixed at 0.6 cm−1. 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.52

I0 is a scaling factor, P(q) the form factor of the micelles, and S(q) the structure factor describing the correlations of the micelles. Iagg(q) denotes the scattering from large aggregates formed by the micelles, and Ifluct(q) describes concentration fluctuations. Ibg denotes the constant background. For S(q), the Percus−Yevick hard-sphere structure factor was used.43 It comprises the hard-sphere radius, RHS, i.e., half the center-tocenter distance between the particles, and the hard-sphere volume fraction, η, i.e., the fraction of micelles which are correlated. For Iagg(q), the Porod form factor44 was used, which gives a scaling factor, IP, and the Porod exponent, α, 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.45 For Ifluct(q), in most cases, the Ornstein−Zernike term was used, which describes concentration fluctuations in solutions of noncharged polymers.46 It contains a scaling factor, IOZ, and a correlation length, ξOZ. In some cases, the solvation term, Isolv(q), was instead used for Ifluct(q). It describes concentration fluctuations in semidilute polyelectrolyte solutions and features a maximum at a finite q value for charged solutions.47 It contains the parameter C characterizing the solvation intensity, the solvation Porod exponent, m, which is expected to be 5/3 for a polymer coil in a good solvent in the case of noncharged polymers, while m = 2 corresponds to a Gaussian coil in a theta solvent;48 a correlation length, ξsolv; and the peak position, q0, which 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.

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RESULTS Molecular Characteristics of the Block Copolymers. The block copolymers PSBP80-b-PNIPAM100 and PSBP80-bPNIPMAM115 (Figure 3) have been obtained by straightforward chain extension polymerization of the polysulfobetaine block in homogeneous solution in trifluoroethanol by the RAFT method. As acrylamides polymerize much faster than their analogous methacrylamides, the chain extension polymerization of NIPMAM was conducted with a higher monomer concentration and for a longer time than for NIPAM under otherwise identical conditions. Still, the conversion of the latter was much higher so that comparable lengths of the nonionic blocks were obtained (Table 1). Because of the use of the naphthalimide-functionalized low molar mass RAFT agent for producing the PSBP block, the block copolymers are also labeled by this solvatochromic fluorophore. Despite its rather hydrophobic character, the dye end group was shown to affect the only weakly the cloud point of polysulfobetaines only weakly.26,32 The molecular characteristics of the copolymers are summarized in Table 1. D


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Macromolecules The 1H NMR spectra of diblock copolymer PSBP80-bPNIPMAM115 and of the underlying homopolymers in aqueous solution are illustrated in Figure 4. The spectra show the broadened signals typical for polymers. As the sharp signals of

the monomers are missing in the spectra, the polymers are clean and free from residual monomer. The overlay of the temperature-dependent spectra of the block copolymer in Figure 4c is instructive but also surprising. In fact, the signals characteristic for the PNIPMAM block (e.g., the signal of the methine signal of the isopropyl group at about 3.9 ppm) are well visible at low temperatures (cf. Figure 4b) but become increasingly broadened and attenuated above 45 °C. In contrast, the signals characteristic for the PSBP block (e.g., the signal of the methylammonium groups at about 3.2 ppm) are well resolved only in brine (Figure 4a). For the block copolymer in pure D2O, the PSBP signals are broadened throughout the whole temperature window studied from 25 to 85 °C. The signals are broadest and most attenuated in the intermediate temperature range of about 55−75 °C. Such a signal broadening and attenuation can be caused by reduced mobility and/or reduced hydration of the polymer chains. While the temperature profile of the evolution of the PNIPMAM-derived proton signals may be easily accounted for by the passage through the coil-to-globule collapse LCST transition, the temperature profile of the PSBP-derived signals is less obvious. Presumably, the complex evolution of the PSBP signals with increasing temperature is the consequence of two counteracting effects that superimpose. On the one hand, increasing temperature will favor hydration of the zwitterionic chains and thus reduces signal broadening and attenuation. This scenario corresponds to the one reported recently for “schizophrenic” block copolymers made of sulfobetaine methacrylates and PNIPMAM.18 On the other hand, the increasingly dehydrating PNIPMAM blocks seem to interact notably with the PSBP blocks, thus counteracting the effect of the passage through the UCST transition and immobilizing the zwitterionic blocks. Such an attractive interaction seems to be particularly strong for the combination of the PSBP and PNIPMAM blocks, possibly due to the increased content of hydrophobic fragments in these polymers compared to e.g. the previously studied combination of PSPP and PNIPAM, for which temperature-dependent NMR spectra did not show a comparable effect.10 Also, an attractive interaction between the zwitterionic and the nonionic blocks seems to be favored by the simultaneous presence of secondary amide moieties in both blocks, enabling mutual H-bonding, as the temperaturedependent NMR spectra of structurally similar block copolymers of sulfobetaine methacrylates and PNIPMAM did behave as may be expected. For the latter, the signals of the zwitterionic and nonionic blocks are most narrow and intense above CPUCST and below CPLCST, respectively.18 Overall Phase Behavior. The CPUCST value of PSBP80 at 50 g L−1 is 78.2 ± 0.5 °C in salt-free D2O, as determined using turbidimetry in a cooling run.27 This value is significantly higher than the CPLCST values of PNIPAM (∼32 °C) and PNIPMAM (∼44 °C), and thus, we do not expect to observe an intermediate regime II (Figure 2) with high light transmission as in the PSPP-b-PNIPAM or PSPP-b-PNIPMAM systems.32,33 Indeed, the light transmission of a 50 g L−1 salt-free solution of PSBP80-b-PNIPAM100 in D2O remains below 3% throughout the entire temperature range (Figure 5a). Upon addition of 0.004 M NaBr, the transmission is slightly enhanced (to ca. 4.0%) in the range 27.0−34.5 °C, which we attribute to a shift of CPUCST of the PSBP block to lower temperatures. This intermediate increase of transmission with temperature is presumably due to the onset of the dissolution of the PSBP blocks; however, the LCST of the PNIPAM block sets in before

Figure 4. 1H NMR spectra of (a) PSBP80 in dilute aqueous NaCl (0.9 g L−1) in D2O at 25 °C, (b) PNIPMAM195 in D2O at 25 °C, and (c) PSBP80-b-PNIPMAM115 in D2O (5 wt %) at different temperatures (25−85 °C). E


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the UCST transition is completed. In analogy to our previous studies on aqueous solutions of PSPP-b-PNIPAM and PSPP-bPNIPMAM, we denote the three regimes as I, II, and III, taking into account the polymers are presumably not molecularly dissolved in regime II. Using PNIPMAM as the LCST block has the advantage that its CPLCST is higher than the one of PNIPAM, which might enlarge regime II. The solutions (salt-free or with 0.002 or 0.004 M NaBr) show in general very low transmission values, but nevertheless, all feature a sharp decrease at 43 °C which is attributed to CPLCST of PNIPMAM (Figure 5b). In salt-free D2O, the transmission increases smoothly from ca. 3.2% to 3.7% when heating from 15 to 43 °C, whereas the solutions containing 0.002 or 0.004 M NaBr show a plateau at 3.5% between 33 and 43 °C or at 3.8% between 27 and 43 °C, respectively. Thus, the onset of the UCST transition of the PSBP block decreases with increasing NaBr concentration, in line with the known salt sensitivity of PSBP.27 Again, we define regimes I, II, and III, as indicated in Figure 4b. To summarize, characteristic changes in the light transmission are encountered: In narrow regions (few °C) close to the CPLCST of the nonionic block, the transmission values are slightly increased. Temperature-Dependent Morphologies. To characterize the structural changes in the three regimes in detail, we carried out SANS measurements in wide temperature ranges around this region. We discuss first the effect of the nature of the nonionic block (PNIPAM or PNIPMAM). Then, the effect of salt on PSBP80-b-PNIPAM100 and PSBP80-b-PNIPMAM115 is investigated. Finally, we derive partial phase diagrams for these samples. Effect of the Nature of the Nonionic Block. To characterize the structural changes in dependence on temperature, SANS investigations of PSBP80-b-PNIPAM100 and

Figure 5. (a) Transmittance of PSBP80-b-PNIPAM100 and (b) PSBP80b-PNIPMAM115 at a concentration of 50 g L−1 in salt-free D2O (black squares), in 0.002 M NaBr in D2O (pink circles), and in 0.004 M NaBr (green triangles) in D2O. The dashed lines indicate the onset of the CPUCST in 0.002 M NaBr (pink) and in 0.004 M NaBr (green) and the CPLCST in all solutions (blue). The three regimes are indicated by Roman letters at the top.

Figure 6. SANS curves from 50 g L−1 salt-free solutions of PSBP80-b-PNIPAM100 (a, c) and PSBP80-b-PNIPMAM115 (b, d) in D2O (symbols). For clarity, only every third point is shown. Full lines: fitting curves obtained using eq 1. In (c, d), the curves are shifted vertically by a factor of 50 with respect to each other. Blue and red color indicate regimes I and III, respectively. F


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Figure 7. Symbols: representative SANS curves from 50 g L−1 PSBP80-b-PNIPAM100 (a, c) and PSBP80-b-PNIPMAM115 (b, d) solutions in D2O at the temperatures given in the graphs. For clarity, only every third point is shown. Full black lines: overall model fits. The broken lines indicate the contributions to the models as described in the graphs.

The contributions are shown separately in Figure 7. Excellent fits are obtained in all cases (Figure 6). We note already here that between regimes I and III, a change of micellar shape occurs for both systems. The most important fitting parameters for both samples are given in Figure 8; complete sets are compiled in Tables S1−S4 of the Supporting Information. For PSBP80-b-PNIPAM100 in regime I (10−30 °C), the radius of the spherical micelles is ravg = 14 ± 2 nm with a polydispersity of 0.22−0.28 (Figure 7, left panel). The hardsphere radius, RHS, is 25 ± 4 nm, which is almost twice ravg. The volume fraction of correlated micelles, η, decreases from ∼0.15 at 10 °C to ∼0.04 at 30 °C. The initially weak correlation between the micelles becomes even weaker upon heating toward CPLCST. The Ornstein−Zernike correlation length, ξOZ, increases from 1.5 ± 0.2 nm at 10 °C to 3.6 ± 0.3 nm at 30 °C. Thus, the polymer structure loosens up upon heating. The forward scattering is very weak, indicating a low fraction of large aggregates. The Porod exponent, α, is 4.0 ± 0.3, indicating that their surfaces are smooth. In regime III, the curve shapes are complex and differ markedly from the ones in regime I. The micelles are now flexible cylinders with radii, rcyl, of 10.6−11.9 nm with a moderate polydispersity, the contour length, L, increasing from 23 ± 2 nm at 40 °C to 36 ± 4 nm at 50 °C, and the Kuhn length, b, increasing from 10 ± 1 to 15 ± 2 nm. Since the ratio L/b is constant (∼2.3), the cylinder stiffness is independent of the temperature in this range. Also, RHS increases upon heating, namely, from 19 ± 2 nm at 40 °C to 22 ± 2 nm at 40 °C, i.e., it lies between rcyl and L. η is ∼0.48. As this value is much higher than in regime I, the micelles are more strongly correlated. This points to the fact that now PSBP forms the shell, in contrast to regime I, where PNIPAM is expected to form the shell of the micelles. The presence of a PSBP shell is in accordance with the fact that the solvation term has to be used instead of the Ornstein−Zernike term. The correlation length, ξsolv, increases from 4.7 ± 0.4 nm at 40 °C to 7.9 ± 0.8 nm at 50 °C, which reflects a loosening of the PSBP shell. The distance of correlations, d0, is ∼15 nm, i.e., similar to rcyl. The solvation

PSBP80-b-PNIPMAM115 in salt-free D2O were carried out. The curves are shown in Figure 6. In both sample systems, two regimes are discernible, which are attributed to regimes I and III in accordance with the turbidity measurements (Figure 5). In regime I, the SANS curves of the PSBP80-b-PNIPAM100 solution feature a smooth decay with a shallow maximum at q ∼ 0.1 nm−1. In regime III, a strong decay is present up to ∼0.09 nm−1 (named forward scattering) along with a pronounced peak at 0.16−0.17 nm−1 and two weak peaks at ∼0.30 and 0.44 nm−1. As detailed below, these peaks are due to the hard-sphere structure factor and the solvation term. The curves of the PSBP80-b-PNIPMAM115 solution are similar, except for two differences: (i) The intensity of the shallow maximum in regime I decreases upon heating to 45 °C. (ii) In regime III, only two peaks are observed (a pronounced one at 0.14 nm−1 and a weak one at 0.4 nm−1) with the second peak gaining intensity upon heating to 65 °C. In the curve of the PSBP80-b-PNIPAM100 solution, the change from regime I to III is observed in the region of 30−40 °C, in agreement with the CPLCST found at ∼34 °C using turbidimetry. In the PSBP80-b-PNIPMAM115 solution, the change of the SANS curve shape is found at 45−50 °C, i.e., at a temperature slightly higher than the value of CPLCST = 43 °C found by turbidimetry. This slight mismatch may be due to different temperature protocols in turbidimetry and SANS (see the Experimental Section). To analyze the structures, model fits were carried out (see the Experimental Section). For all curves, the structure factor, reflecting the interaction between the micelles, is well described by a hard-sphere structure factor. The forward scattering at low q values is described by the Porod law, i.e., very large aggregates are present, especially in regime III, with their size exceeding the resolution of the instrument. The model in eq 1 fits the curves well when the sphere form factor along with the Ornstein−Zernike structure factor are used in regime I (10−30 °C for PSBP80-b-PNIPAM100 and 20−45 °C for PSBP80-bPNIPMAM115). At higher temperatures, i.e., in regime III, the cylinder form factor and the solvation term are used instead. G


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This may be due to attractive interactions between the blocks in regime III, in analogy to the discussion of the temperaturedependent NMR spectra above. The Porod exponent related to the large aggregates, α, is ∼4.8, indicating compact aggregates with a concentration gradient near the surface. These aggregates are prominent, as evident from the strong forward scattering. We conclude that in salt-free D2O PSBP80-bPNIPAM100 forms spherical micelles, which are only weakly correlated, in regime I, whereas short, flexible, cylindrical micelles with PSBP at the surface are encountered in regime III above CPLCST of PNIPAM. These are strongly correlated and form large aggregates. A very similar picture emerges for PSBP80-b-PNIPMAM115 (Figure 8, right panel), with the following differences: In regime I, ξOZ is larger than in PSBP80-b-PNIPAM100. It describes probably the correlations among the LCST block, which is different in the two diblock copolymers. The average sphere radius, ravg, is however, the same in both diblock copolymers and thus rather related to the core formed by the PSBP blocks. In regime III, the contour length of the cylinders, L, increases strongly with increasing temperature (from 25 ± 2 nm at 50 °C to 54 ± 5 nm at 65 C), whereas the Kuhn length stays 16−18 nm. This results in a ratio L/b which increases from 1.7 at 50− 60 °C to 3.0 at 65 °C. Therefore, the cylinders become more flexible at this highest temperature, probably due to a weakening of the attractive interactions among the PSBP blocks as a consequence of the crossing of the CPUCST of PSBP in this temperature range (60−65 °C). The core−shell structure of the micelles expected in regimes I and III could not be resolved. This may be due to ionic interactions between the PSBP blocks in regime I and the interactions between the PSBP and the PNIPAM/PNIPMAM blocks in regime III, as found using 1H NMR (Figure 4). Still, the interactions between the micelles are different in the two

Figure 8. Fitting results from the SANS curves in Figure 6. (a−e) PSBP80-b-PNIPAM100; (f−j) PSBP80-b-PNIPMAM115 in salt-free D2O in dependence on temperature. (a, f) Micellar radius, ravg (closed square), cylinder radius, rcyl (open square), cylinder contour length, L (filled triangle right), and the hard-sphere radius, RHS (open circle). (b, g) Ornstein−Zernike correlation length, ξOZ, (c, h) polydispersity of the micellar/cylinder radius, p, (d, i) hard-sphere volume fraction, η, (e, j) Porod exponent, α. Blue dashed lines: CPLCST values from turbidimetry. Regimes I and III are indicated at the top.

Porod exponent, m, decreases from 1.4 ± 0.1 at 40 °C to 0.9 ± 0.1 at 50 °C, which indicates worsening solvent conditions.

Figure 9. (a) SANS curves from 50 g L−1 solutions of PSBP80-b-PNIPMAM115 in salt-free D2O (open symbols) and in 0.004 M NaBr in D2O (closed symbols). For clarity, only every third point is shown. Full lines: fitting curves obtained using eq 1. The curves are shifted vertically by a factor of 50 with respect to each other. Blue, green, and red color indicate regimes I, II, and III. (b−f) Fitting results in salt-free D2O (black symbols) and in 0.004 M NaBr in D2O (red symbols). Same designations as in Figure 7. Red dashed line: onset of CPUCST; blue dash-dotted line: CPLCST from Figure 5b. Regimes I, II, and III are indicated in the top. H


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correlated micelles is slightly higher (Figure 9e). ξOZ is slightly lower lower (Figure 9c) and and may contain contributions not only from the PNIPMAM shell (as in regime I) but also from the inside of the spheres. In regime III, all fitting parameters are very similar to those in salt-free D2O: Only ξsolv is a little larger, which reflects the screening effect of salt on the chain conformation of the PSBP block forming the shell. The temperature range 35−45 °C may be identified as regime II, where the attractive interactions between PSBP are weakened compared to lower temperatures. As previously found with the PSPP-b-PNIPAM and PSPP-b-PNIPMAM systems,32,33 the model in eq 2 may also be used to fit the curves in regime II (Figure 10b and Table S7). These fits describe the data equally well. The model comprises the Porod term to describe scattering from large aggregates and the solvation term which gives detailed information about the correlations. The correlation length, ξsolv, decreases from 8.6 ± 0.6 nm at 35 °C to 5.1 ± 0.3 nm at 45 °C. While at 35 °C, the scattering from the shell dominates, at 45 °C, also the PSBB core may contribute to ξsolv. The solvation Porod exponent, m, is 2.0 ± 0.2, indicating theta solvent conditions. d0 increases from 85 ± 7 nm at 35 °C to 105 ± 10 nm at 45 °C. These large values indicate a dissolved state of both blocks, which is the result of weakened ionic attractions between the PSBP blocks and of the stiff chain conformation of the PNIPMAM block below CPLCST.41

regimes, in agreement with different blocks being present at the surface of the spheres/cylinders. Electrolyte Effect. For both diblock copolymers, the addition of NaBr has an impact on the transmission curves (Figure 5): A temperature range with slightly increased transmission (27.0−34.5 and 27.0−43.0 °C for PSBP80-bPNIPAM100 and PSBP80-b-PNIPMAM115, respectively) is observed. We investigate here the structural changes of PSBP80-b-PNIPMAM115 in 0.004 M NaBr in D2O using SANS in a temperature window around the region of enhanced light transmission, with the aim of detecting whether regime II is encountered in this region. The SANS curves of PSBP80-b-PNIPMAM115 in 0.004 M NaBr in D2O are shown in Figure 9a along with the ones in salt-free D2O. At 20−45 °C, the curves show significantly decreased scattering at q < 0.2 nm−1. This is especially pronounced at 35−45 °C, and we refer to this temperature range as regime II, even though the UCST transition of the PSBP block has not been completed. At 45−65 °C, the curves are nearly unchanged by the addition of NaBr. We used for the salt-containing solutions the same fitting model as for the curves in salt-free D2O (Figure 10a). The most important fitting parameters for both samples are given in Figure 9b−f, while complete sets are compiled in Tables S5 and S6. In regime I (referring to salt-free D2O), i.e., at 20−30 °C, the main difference is that 0.004 M NaBr, ξOZ is 2−3 nm higher. At 30−45 °C, the sphere radius, ravg, is significantly smaller (2−3 nm, Figure 9b), and the polydispersity is higher (Figure 9d). RHS is by 6 nm smaller (Figure 9b), and the volume fraction of

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CONCLUSION Based on the turbidimetry and SANS results, the phase behavior of aqueous solutions of PSBP80-b-PNIPAM100 and PSBP80-b-PNIPMAM115 is established, the latter also in 0.004 M aqueous NaBr (Figure 11). In PSBP80-b-PNIPAM100,

Figure 11. Schematic representations of the phase diagrams of (a) PSBP80-b-PNIPAM100 in dependence on temperature and (b) PSBP80b-PNIPMAM115 in dependence on temperature and NaBr concentration, resulting from SANS. Red: PSBP block; blue: PNIPAM/ PNIPMAM block. Red dashed line: CPUCST of the PSBP block; blue dash-dotted line: CPLCST of the PNIPAM/PNIPMAM block.

spherical micelles with a PNIPAM shell are formed below the CPLCST of PNIPAM and cylindrical micelles with a PSBP shell above (Figure 11a). A similar behavior is encountered for PSBP80-b-PNIPMAM115 (Figure 11b). Upon addition of NaBr, an additional regime (regime II) appears at intermediate temperatures. In this regime, the interactions are weakened, and no micelles are present. It is instructive to compare the behavior of the present systems with the ones of PSPP432-b-PNIPAM200 and PSPP498-bPNIPMAM144 studied before.32,33 At this, one has to keep the

Figure 10. Symbols: representative SANS curves from a 50 g L−1 PSBP80-b-PNIPMAM115 solution in 0.004 NaBr in D2O at 40 °C. Symbols: experimental data. For clarity, only every third point is shown. Full black lines: overall model fits. The broken lines indicate the contributions to the models as described in the graphs. (a) Fit obtained using eq 1; (b) fit obtained using eq 2. I


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following aspects in mind: (i) The PSBP blocks are more hydrophobic than the PSPP blocks, as evident from the higher CPUCST values of the corresponding homopolymers.27 (ii) The PSBP blocks in the present diblock copolymers have lower weight fractions than the PSPP blocks had in the PSPPcontaining diblock copolymers. (iii) The overall molar masses of the PSPB diblock copolymers studied here are much lower than the PSPP-containing diblock copolymers studied previously. One main difference is that regime II (with full dissolution, double hydrophilic state) is not observed in the salt-free solutions of PSBP80-b-PNIPAM100 or PSBP80-b-PNIPMAM115. This is due to the higher CPUCST value of PSBP compared to the one of its homologue PSPP. Thus, the attractive interaction between the PSBP segments may be assumed to be stronger in the entire temperature range investigated than the interaction between the PSPP segments. While nothing can be said about the CPUCST of the PSBP blocks, since it is preempted by the CPLCST of the PNIPAM/PNIPMAM block, the latter seems to be unaffected by the presence of the PSBP block. The structures of the micelles in regimes I and III are different for the two series of “schizophrenic” diblock copolymers as well. In PSPP432-b-PNIPAM200, the micelles in regime I are more disperse and less correlated than the ones in PSBP80-b-PNIPAM100,32 which may be due to the stronger tendency of PSBP to aggregation. In regime III, the shape of the micelles differs significantly: Whereas spherical micelles with a distinct core−shell structure are formed in PSPP432-bPNIPAM200, cylindrical micelles without a detectable core− shell structure are observed for PSBP80-b-PNIPAM100. This may be due to the difference in the relative sizes of the nonionic and the zwitterionic blocks. The correlation between the micelles in PSBP80-b-PNIPAM100 is more pronounced for PSPP432-b-PNIPAM200, corroborating the stronger attractive interaction between the PSBP blocks even at the highest temperatures studied. Similar remarks can be made for the micelles in regimes I and III of PSPP498-b-PNIPMAM144 and PSBP80-b-PNIPMAM115. In PSBP80-b-PNIPMAM115, the addition of NaBr results in the appearance of regime II, where no micelles are present and the behavior is similar to the one of polyelectrolytes. As a consequence, we have realized a truly orthogonally switchable system, where both temperature and salt content may serve as a trigger. We anticipate that a higher fraction of PSBP in PSBP-bPNIPMAM will implement the full scenario depicted in Figure 2b.

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Peter Müller-Buschbaum: 0000-0002-9566-6088 André Laschewsky: 0000-0003-2443-886X Christine M. Papadakis: 0000-0002-7098-3458 Present Address

K.N.R.: Cracow University of Technology, Department of Chemistry and Technology of Polymers, Warszawska 24, 31155 Kraków, Poland. Funding

We thank Deutsche Forschungsgemeinschaft (DFG) for financial support (PA 771/14-1, MU 1487/17-1, LA 611/11-1). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank A. Lieske and M. Walter (Fraunhofer IAP) for support by SEC measurements. This work is based upon experiments performed at the KWS-1 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. We acknowledge beamtime allocation and excellent equipment.

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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.8b00096. Tables with fitting parameters; IR spectra of the diblock copolymers; GPC elution curves for the diblock copolymers (PDF)

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REFERENCES

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


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