Concentration Fluctuations near Lower Critical Solution Temperature

Sep 7, 2017 - Although DLS data clearly show that aggregates can form as precursors in the homogeneous one-phase region depending on the TMAO concentr...
0 downloads 8 Views 2MB Size
Download PDF
Article pubs.acs.org/Macromolecules

Concentration Fluctuations near Lower Critical Solution Temperature in Ternary Aqueous Solutions Di Jia,†,‡ Murugappan Muthukumar,§ He Cheng,*,†,‡ Charles C. Han,*,∥ and Boualem Hammouda⊥ †

China Spallation Neutron Source (CSNS), Institute of High Energy Physics (IHEP), Chinese Academy of Sciences (CAS), Dongguan 523803, China ‡ Dongguan Institute of Neutron Science (DINS), Dongguan 523808, China § Department of Polymer Science and Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States ∥ Institute for Advanced Study, Shenzhen University, Shenzhen, 518060, China ⊥ Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899-6102, United States S Supporting Information *

ABSTRACT: The effects of osmolytes, such as trimethylamine N-oxide (TMAO), on the phase transition in an aqueous solution of polymer, protein, or DNA are very complex, and several phase transitions can occur. In order to explore such effects, we take a simple ternary system of poly(N,N-diethylacrylamide) and a favorable solvent pair TMAO and water to monitor the reduction in the miscibility of the polymer using small-angle neutron scattering (SANS) and dynamic light scattering (DLS). The result shows that the LCST of PDEA solutions is significantly depressed by TMAO. Although DLS data clearly show that aggregates can form as precursors in the homogeneous onephase region depending on the TMAO concentration, after removing the low-q aggregate region, the three-component system still obeys the mean-field theory. Based on the ternary random phase approximation (RPA) theory, three Flory−Huggins interaction parameters, i.e., χD2O−TMAO, χPDEA−TMAO, and χPDEA−D2O, are obtained to reveal the microscopic origin of this shift in LCST; that is, the strong TMAO−D2O interaction leads to the decrease of LCST. Our study opens up many directions to explore effects such as the interference between aggregation and microphase separation.

1. INTRODUCTION Adding the cosolvent can either enhance or decrease the solvation of polymers. Cosolvency and co-nonsolvency are two extreme phenomena. If a mixture of two nonsolvents forms a good solvent for a polymer, that is cosolvency; reversely, if a mixture of two good solvents forms a poor one for a polymer, that is co-nonsolvency. The origin of co-nonsolvency has been argued for decades. Currently there are two classes of explanations: the strong solute−solvent interactions and the strong solvent−solvent interactions. For example, Kremer et al. applied the adaptive resolution scheme (AdResS) method with a Metropolis particle exchange criterion to the reentrant behavior of PNIPAM in water/methanol mixture solvents and found that the origin of such a re-entrance is due to the preferential solute−solvent interactions. In the concentration range where polymer collapses into globule, the average number of hydrogen bonds between PNIPAM and solvent molecules decreases about 20%.1−3 Another example is “competitive adsorption”,4−8 which focuses on the cooperative competition between polymer−water hydrogen bonds and polymer−organic solvent hydrogen bonds. Note that this assumption assumes the solvent−solvent interaction is much weaker than the solvent−polymer interaction, so that they can © XXXX American Chemical Society

be neglected. However, others point out that the strong solvent−solvent interactions such as concentration fluctuation can prevent the solvent−polymer interaction, leading to the cononsolvency. For example, Hao et al. combined the small-angle light scattering (SANS), light scattering, and viscometry to prove that the collapse of PNIPAM-co-PEG microgel in the THF−water mixture solvent happens when the composition fluctuation in THF−water mixture get maximum at 20 mol % THF content, and such a composition fluctuation leads to the co-nonsolvency phenomena.9 Moreover, Zhang et al. used light scattering to prove that the coil−globule−coil transition of PNIPAM chains in water/methanol mixtures with increasing methanol content is induced by the formation of water/ methanol complexation; that is, the solvent−solvent interaction is so strong that a stoichiometric compound/complexation between them is formed and can be considered as a new “bad solvent”.10,11 However, direct evidence of such complexation still lacks. Freed et al. refined the classic Flory−Huggins (FH) theory to consider the mutual association of the solvent Received: July 14, 2017 Revised: August 24, 2017

A

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

(RAFT) according to the literature.21,26 The molar ratio of the monomer DEA:chain transfer agent cumyl dithiobenzoate (CDB):initiator AIBN was 600:1:0.2. 9.9500 g of DEA, 0.0355 g of CDB, and 0.0043 g of AIBN were dissolved in 10 mL of DMF and then put in a polymerization tube. After being frozen and thawed three times in order to remove oxygen, the tube was then put in an oil bath at 60 °C and stirred for 5.6 h. After the reaction, the mixture was cooled to room temperature and dissolved in 30 mL of acetone and then precipitated from 600 mL of hexane. Finally, the product was dried in a vacuum oven at room temperature overnight. 2.2. Dynamic Light Scattering (DLS). Dynamic light scattering (DLS) measurement was carried out on a commercial LS spectrometer equipped with a multi-τ digital time correlator (ALV5000) and four lasers with different wavelengths.27 A cylindrical 22 mW UNIPHASE He−Ne laser (λ0 = 632.8 nm) was used to perform the test. The sample cell is held in a thermostat index matching vat filled with purified and dust-free toluene, with the temperature controlled to within 0.1 °C. The scattering angle is 30°. The baseline-normalized intensity−intensity time correlation function g2(t) − 1 in the selfbeating mode was measured. The CONTIN program was used to calculate the hydrodynamic radius distribution.28 From the translational diffusion coefficient, the hydrodynamic radius Rh can be determined from the Stokes−Einstein relation Rh = kBT/6πηD, where kB, T, and η are the Boltzmann constant, the absolute temperature, and the mixed solvent viscosity, respectively.29 2.3. Ultraviolet−Visible (UV−Vis) Spectroscopy. A UV-2450 UV−vis spectrophotometer equipped with a San Ace 60 temperature control unit was used to measure the absorbance and transmittance of the solutions. The wavelength was scanned from 200 to 800 nm for the absorption study, and then the wavelength was set at 632.8 nm for the transmittance experiment. Standard quartz cuvettes with a path length of 10 mm were used.21 2.4. Small-Angle Neutron Scattering (SANS). SANS was performed on the NGB30 instrument at the National Institute of Standards and Technology, Center for Neutron Research (NCNR, Gaithersburg, MD). It was taken for three sample-to-detector distances of 1, 4, and 13 m. The neutron wavelength is 6 Å at 1 and 4 m and 8.4 Å at 13 m sample-to-detector distances. The different wavelength at the 13 m sample-to-detector distance is due to the use of lenses to focus the neutron. In SANS, the essential measurement length scale is the reciprocal of the scattering vector 1/q, with q = 4π/λ sin(θ/2), where θ is the scattering angle and q is in the range of 0.001−0.4 Å−1 in our measurement.

molecules and found that a large negative solvent−solvent interaction parameter is a necessary condition for the occurrence of co-nonsolvency in ternary polymer solutions.12,13 Because of the co-nonsolvency effect, several phase transitions can occur. For example, semidilute poly(ethylene oxide) (PEO) solutions in water phase separate upon heating and therefore obey a lower critical solution temperature (LCST) phase behavior, while they exhibit an upper critical solution temperature (UCST) phase behavior in ethanol. When PEO dissolved in ethanol/water mixtures, there is a transition from UCST to LCST as the water fraction in the solvent mixture increases.14 Reddy et al. combined fluorescence spectroscopy, viscosity meter, light scattering, and Fourier transform infrared spectroscopy to study the phase behavior of poly(N-isopropylacrylamide) (PNIPAM) in trimethylamine Noxide (TMAO)/water mixture solvent, and they found the LCST value decreases with increasing TMAO concentration, which is mainly attributed to the direct hydrogen bonding of TMAO with the water molecules that are bound to the amide functional groups of the PNIPAM and thus the breakage of the hydrogen bonding between PNIPAM and the bounded water molecules.15 However, some all-atom molecular dynamics simulations showed that the hydrogen bonds between water molecules and PNIPAM would be strengthened in the presence of TMAO.16 Note that since the polymer−mixed-solvent solution is a single system, not only the entropy variation of the bound water around the polymer but also the structure change of the whole solvent should be considered.17 Although lots of experiments and simulations have been conducted for the co-nonsolvency phenomena in ternary polymer solutions,18−22 how the third component influences the liquid−liquid phase separation still remains unknown. In order to explore such an effect and clarify the above diverging argument, the phase behavior of poly(N,N-diethylacrylamide) (PDEA) in the TMAO/water mixture was studied by combined SANS and DLS measurements and the implementation of random phase approximation theory. PDEA lacks active hydrogen atom compared to PNIAPM23 so that we can monitor clearly how the cosolvent influences the phase behavior of the polymers. Our results show that there is a simultaneous occurrence of aggregation and significant composition fluctuations near the LCST of the liquid−liquid phase separation. We have quantified the sizes of aggregates and the nature of composition fluctuations and also have determined the molecular origin behind this phenomenon by determining the various Flory−Huggins chi parameters. Although aggregates are observed as precursors in the homogeneous phase with controllable amount of TMAO, after removing the low-q aggregation region, the threecomponent system still obeys the mean-field theory of an essentially two-component Ising system24 by fitting the SANS data. Our study opens up many directions to explore effects such as the interference between aggregation and microphase separation and might also help understand how TMAO acts as a protective osmolyte25 to stabilize the protein native structures.

3. RESULTS AND DISCUSSION 3.1. Dynamic Light Scattering. PDEA was calibrated first. Figure 1a is the intensity−intensity time correlation function of PDEA in pure D2O at 23 °C. It clearly demonstrates that there is only one mode in PDEA aqueous solution below LCST. The Laplace transform of the correlation function is the corresponding hydrodynamic radius distribution, which is monodisperse and centers at Rh = 4.6 nm. Then TMAO concentration dependence of hydrodynamic radius was measured. When TMAO is introduced into the aqueous solution, a slow mode emerges, as shown in Figure 1b. Note that the hydrodynamic radius is dependent on the inverse of the mixed-solvent viscosity, so the viscosity correction has to be made.30,31 The fast mode is due to the Brownian diffusion of the PDEA coil, and the slow mode may be due to the PDEA aggregates.32 The hydrodynamic radius of the unaggregated PDEA coil shrinks little from 4.6 to 4.2 nm, once TMAO is added, and then it keeps constant with the increase of TMAO concentration until 0.9 mol/L at the same temperature. The further increase of TMAO concentration leads to the precipitation of PDEA, and we will discuss this later. The fact that the hydrodynamic radius of polymer coil is independent of TMAO concentration implies that there is no direct interaction

2. EXPERIMENTAL SECTION 2.1. Material. D2O and trimethylamine N-oxide (d9, 98%) were bought from Cambridge Isotope Lab, Inc., and used as received. The excess volume of solvent mixing can be ignored since TMAO is powder and its mass fraction is very low. PDEA was synthesized by reversible addition−fragmentation chain transfer polymerization B

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 1. (a) Typical normalized intensity−intensity time correlation function g(2)(t) − 1 of 2.94 mg/mL PDEA in pure D2O at 23 °C at θ = 30°. The inset is the corresponding hydrodynamic radius distribution. (b) TMAO concentration dependence of two-mode hydrodynamic radius in 2.94 mg/mL PDEA/TMAO/D2O mixture at 23 °C, where M denotes mol/L.

Figure 2. SANS profiles of 4% mass fraction PDEA in TMAO-d9/ D2O mixtures. (a) Temperature dependence of PDEA at CTMAO = 0.28 M; the arrow is used to guide the eye, indicating the increase of concentration fluctuations with temperature. (b) TMAO concentration dependence at 15 °C when TMAO concentrations are 0, 0.1, 0.28, 0.44, 0.58, 0.76, 0.90, 1.13, and 1.25 M. The red lines are the best fits to eq 1.

between TMAO and PDEA polymer chains. At the same time, the slow mode increases from 86 to 98 nm, indicating that the aggregate size becomes larger with TMAO concentration. 3.2. Mapping the Phase Diagram. DLS gives us a general feature of the effects of TMAO on the structure variation of PDEA aqueous solution. On one hand, TMAO may not directly interact with PDEA because ⟨Rh⟩ of the PDEA coil has no TMAO concentration dependence. On the other hand, the PDEA aggregates form in the one-phase region before liquid− liquid phase separation happens (phase diagram shown in Figure 5). The TMAO−D2O interaction may be so strong that the mixture solvent becomes a poorer solvent for PEDA; therefore, part of the polymer forms aggregates. To further reveal thermodynamics in the ternary mixture, detailed phase behavior of PDEA in TMAO/D2O mixtures was studied by SANS. As temperature increases, the amplitude of concentration fluctuation increases (Figure 2a). When it is close to the phase boundary at 27 °C, concentration fluctuation becomes larger. TMAO concentration dependence of SANS profiles at 15 °C is presented in Figure 2b; the amplitude of fluctuations increases continuously with TMAO concentration when it is close to the phase boundary. We should note that the upturn in the low-q region might due to the PDEA aggregates. In the one-phase region, a simple empirical model is used to fit the SANS profiles. d Σ(Q ) I(0) A = n + + background dΩ Q 1 + (Qξ)m

fluctuations, which has nothing to do with the real size of PDEA coils in solution; and m is the Porod exponent. The first term A/Qn is used to fit the low-q region data. The second term is the modified Ornstein−Zernike equation. It is used to fit the intermediate and high-q region data and reveal thermodynamics. Nonlinear least-squares fits are performed for all SANS data and the fitting parameters are obtained for the various measuring temperatures and TMAO concentrations (the red fitting lines in Figure 2). The quantities most relevant to demixing thermodynamics are the characteristics of thermodynamics (namely, this given by susceptibility) I(0) and the correlation length ξ. By fitting the SANS data using eq 1, we can get six fitting paramters, that is, A, n, I(0), ξ, m, and background. In order to remove the lowQ aggregation region, I(0) in the second term is used to do the extrapolation. Therefore, plotting I(0)−1 as a function of T−1, where T is the absolute temperature, shows a linear behavior in the one-phase region, as shown in Figure 3. A positive slope represents a LCST type of behavior. Extrapolation of this linear behavior to 1/I(0) → 0 can yield the spinodal temperature. The correlation length ξ increases with temperature (inset of Figure 4). At the same temperature, the correlation length ξ also increases significantly with TMAO concentration. Theoretically, one expects that both I(0) and the correlation length ξ will diverge at the spinodal temperature. The relation between correlation length ξ and temperature based on the mean-field prediction is as follows:33

(1)

where dΣ(Q)/dΩ is the differential scattering cross section; I(0) is the characteristic of thermodynamics (susceptibility); ξ is the correlation length or the length of the concentration

ξ ∼ |Ts − T |−0.5 C

(2) DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 3. I(0)−1 vs T−1 of PDEA in D2O/TMAO mixtures at various TMAO concentrations. The PDEA mass fraction is fixed at 4%. Figure 5. Resultant LCST phase diagram. The open red circles are spinodal points, and the black triangles are cloud points measured by UV−vis. The PDEA mass fraction is fixed at 4%.

chains themselves are unperturbed. Before the SANS experiment, we found the rough phase boundaries by making the UV−vis measurement first to get the cloud points, as shown in Figure 5 (black triangles); they are generally consistent with the spinodal result obtained by SANS within experimental error bars. But we are not sure whether our system is a line of critical points or a collection of first-order transitions (with a finite difference between the binodal and spinodal lines). Besides, the solubility of TMAO-d9 in D2O is about 1.5 mol/L at 17.5 °C, which prohibits any further increase of TMAO concentration in the solution. Note that throughout this paper error bars for the fitting parameters correspond to one standard deviation. 3.3. Ternary Random Phase Approximation. The ternary radom phase approximation (TRPA) is used to analysis the SANS data in the one-phase region, when it is not very close to the critical point, to obtain the three effective interaction parameters, i.e., χD2O−TMAO, χPDEA−TMAO, and χPDEA−D2O. RPA is an approximate model here, but it is proven to be a useful tool to investigate the mixing/demixing thermodynamics of binary homopolymer and copolymer solutions.34 In the article, A/Qn in eq 1 contributes little to the low Q scattering profile; its effects on concentration fluctuactions can thereby be neglected because the scaling behaviors of both I(0) and ξ obey RPA theory well. The ternary RPA model is described briefly as follows. The three components are defined as (1) TMAO, (2) D2O, and (3) PDEA, the degree of polymerization as n1, n2, and n3; the volume fractions as ϕ1, ϕ2, and ϕ3; and the specific volumes as v1, v2, and v3 for the three components. The bare structure factors (when interactions are not included) are expressed as S011 = n1ϕ1ν1, S022 = n2ϕ2ν2, and S033 = n3ϕ3ν3P(Q), where P(Q) is the single chain form factor. Note that the cross-terms such as S012 do not contribute. The following parameters are defined as

Figure 4. Correlation length ξ as a function of (Ts − T)−0.5 at different TMAO concentrations. Inset is the correlation length ξ as a function of temperature at different TMAO concentrations. The PDEA mass fraction is fixed at 4%.

The ξ vs (Ts − T)−0.5 is plotted in Figure 4. The spinodal temperature Ts in eq 2 at different TMAO concentrations is obtained from the extrapolation of I(0)−1 vs T−1 plot in Figure 3. We can see that all the data at different TMAO concentrations collapse to one master curve and fit the relation well. This indicates that the spinodal temperature Ts obtained from divergence of I(0) and divergence of correlation length ξ are consistent with each other. It is convenient to get Ts first from I(0)−1 vs T−1 because it is a linear fit. Although PDEA coils and aggregates coexist in the one-phase region, after removing the low-q aggregation region, the three-component system still obeys the mean field theory of an essentially twocomponent Ising system.24 Although the experimental data with error bars is not sufficient to discriminate between the mean-field and critical behavior, our experiments show that the range of temperature where fluctuations dominate are very narrow and the exponent of divergence of correlation length with ΔT is 0.5, which is the mean field value. The polymer aggregates can act as precursors in the homogeneous phase before liquid−liquid phase separation happens, which needs further investigation. The extrapolated spinodal temperatures and the resultant phase diagram are drawn in Figure 5. It is a LCST type of phase diagram; i.e., below the spinodal temperature the ternary mixture is stable and uniform, and above the spinodal point, the solution undergoes phase separation and it turns turbid. The LCST of the ternary mixture decreases with TMAO concentration, which proves that the addition of TMAO significantly destabilizes the solution, although the polymer D

V11 =

2χ 1 − 13 0 ν13 S33

V22 =

2χ 1 − 23 0 ν23 S33

V12 =

2χ 2χ 2χ 1 + 12 − 13 − 23 0 ν12 ν13 ν23 S33

(3) DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules Table 1. Best Fitting Results for the RPA Model According to Eq 5a E12

TMAO (M) 0 0.10 0.28 0.44 0.58 0.76 0.90 1.13 a

−4.25 −3.01 −2.25 −2.34 −2.15 −2.13 −2.25

± ± ± ± ± ± ±

F12 (K) 0.08 0.00 0.00 0.13 0.19 0.20 0.20

614.03 521.64 347.11 404.20 387.19 414.41 457.27

± ± ± ± ± ± ±

E13

9.87 0.12 0.18 19.00 54.30 35.8 22.30

9.96 6.53 4.52 4.46 3.94 4.03 3.92

± ± ± ± ± ± ±

F13 (K) 0.11 0.00 0.00 0.61 0.28 0.63 0.41

−1421.60 −1070.50 −731.70 −826.83 −736.11 −757.98 −805.32

± ± ± ± ± ± ±

21.40 0.58 0.19 126.00 57.10 29.70 86.90

E23 2.19 0.78 0.88 0.78 0.89 0.91 0.98 1.11

± ± ± ± ± ± ± ±

F23 (K) 0.00 0.02 0.00 0.00 0.08 0.11 0.09 0.77

−240.75 −104.87 −145.29 −113.57 −152.81 −158.27 −181.23 −225.12

± ± ± ± ± ± ± ±

0.00 1.35 0.09 0.06 28.20 13.30 12.6 16.3

Note: (1) TMAO; (2) D2O; (3) PDEA.

in terms of the Flory−Huggins interaction parameters χ12, χ13, and χ23 and the reference volumes ν12 = (ν1ν2)1/2, ν13 = (ν1ν3)1/2, and ν23 = (ν2ν3)1/2. Then the fully interacting system structure factors can be expressed as S11(Q ) =

0 0 (1 + V22S22 ) S11 Δ

S22(Q ) =

0 0 (1 + V11S11 ) S22 Δ

S12(Q ) =

0 0 (1 + V12S22 ) S11 Δ

(4)

The denominator is given by Δ = (1 + + − V212S011S022. The relation Δ = 0 yields the spinodal condition. The SANS macroscopic scattering cross section is given by V11S011)(1

V22S022)

d Σ(Q ) = (ρ1 − ρ2 )2 S11(Q ) + (ρ2 − ρ3 )2 S22(Q ) dΩ + 2(ρ1 − ρ3 )(ρ2 − ρ3 )S12(Q )

Figure 6. Temperature and TMAO concentration dependence of three interaction parameters χTMAO−D2O, χPDEA−TMAO, and χPDEA−D2O. The PDEA mass fraction is fixed at 4%.

(5)

where ρ1, ρ2, and ρ3 are the neutron scattering length density of the different species. For the PDEA/D2O/TMAO mixture, the following parameters are used:

system: when χTMAO−D2O is negative, LCST of PDEA is lowered with the addition of TMAO. χTMAO−D2O increases with TMAO concentration and decreases with temperature; both of them prove that the solubility of TMAO in water is limited, and it increases with temperature. As TMAO concentration increases, TMAO will be more unstable in the water and finally lead to phase separation. The larger χPDEA−TMAO (in Figure 6b) indicates that PDEA−TMAO interaction is extremely weak, so PDEA prefers not to interact directly with TMAO, and it is consistent with DLS observation in Figure 1. Moreover, as TMAO concentration increases, both χPDEA−TMAO and χPDEA−D2O decrease, indicating only when TMAO−D2O interaction becomes weaker, then PDEA has the chance to form stronger interaction with solvent molecules. TMAO concentration and temperature dependence of χPDEA−D2O are interesting. There is an abrupt change when the two-component system becomes a three-component system with the addition of TMAO, which proves that TMAO−D2O interaction will greatly affect PEDA−D2O interaction. At the θ condition, the Flory−Huggins parameter χθ = 1/2 in an ideal binary blend where the partial volumes of the polymers and solvent are assumed to be the same.35 While for PDEA/D2O binary system, χθ is about 1.33 according to our previous calculation in PDEA aqueous solutions.21 Therefore, PDEA is a frustrated coil in water because hydrophobic interactions between polymers tend to repel water molecules, and polymer−polymer attractive interaction is preferred.36 In the

n1 = n2 = 1, n3 = 220, v1 = 9.4 × 10−23 cm 3, v2 = 3.00 × 10−23 cm 3, v3 = 2.11 × 10−22 cm 3, ρ1 = 1.01 × 1011 cm−2, ρ2 = 6.34 × 1010 cm−2, ρ3 = 6.20 × 109 cm−2

Recalling the component numbering (1) TMAO, (2) D2O, and (3) PDEA, the volume fractions of the three components are calculated according to the mass fraction and the density of the mixture: ϕ3 = 0.044, ϕ1 = ϕTMAO(1 − ϕ3), and ϕ2 = 1 − ϕ1 − ϕ3, where ϕTMAO is the TMAO relative fraction in the D2O/ TMAO mixture. Note that the 1/T dependence of the interaction parameters warrants the splitting χij = Eij + Fij/T for all the three χ parameters, for a total of six fitting variables in the ternary RPA fitting process. The fitting results are listed in Table 1. Note that M stands for mol/L. The ternary RPA results are shown in the Figure 6. Generally, smaller negative χ means stronger attractive interactions. In all of the temperature and concentration ranges, χTMAO−D2O are negative and are much smaller than χPDEA−TMAO and χPDEA−D2O (Figure 6a). Freed et al. used simulations to study the effect of cosolvent on the phase transition in ternary polymer solutions, and they found that cononsolvency can happen when solvent−solvent interaction parameters are negative.12 Here, we also proved this in our E

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules PDEA/D2O binary system, χPDEA−D2O is about χθ = 1.33 at room temperature. However, once with the addition of TMAO, χPDEA−D2O decreases abruptly below 1.33, and all the χPDEA−D2O of the PDEA/D2O/TMAO ternary system is within the θregion (Figure 6c). We should also note that χPDEA−D2O increases with temperature and decreases with TMAO concentration (Figure 6c). This is because once TMAO is added, TMAO−D2O interaction competes with both PDEA− D2O and PDEA−TMAO interactions, thus changing the Gibbs free energy of the whole mixture, leading to the decrease of the LCST of polymers. Once TMAO is added in PDEA aqueous solution, it prefers to interact with D2O first (Figure 6a). On the other hand, when TMAO concentration is 0.1 M, χPDEA−TMAO is about 5, which is much larger than χPDEA−D2O or χTMAO−D2O, implying the interaction between TMAO and PDEA polymer chains is rather weak. Moreover, Schild et al.34 studied the co-nonsolvency phenomena and found that the phase behavior of poly(N-isopropylacrylamide) (PNIPAM) in water−methanol mixtures is insensitive to a 200-fold variation in polymer concentration, and the phase behaviors of PNIAPM solutions and gels are similar, which means the co-nonsolvency phenomenon does not rely on polymer concentration. So the PDEA concentration is fixed at 4%, and only the TMAO concentration is changed in this work. As temperature increases, χTMAO−D2O will decrease, which indicates the solubility of TMAO increasing with temperature and contributes to the better interaction of D2O and TMAO. The positive value of χPDEA−TMAO and χPDEA−D2O indicates that PDEA likes neither TMAO nor D2O. χPDEA−TMAO and χPDEA−D2O increasing with temperature indicates that it is a LCST type of phase diagram, so as the temperature increases, the system approaches the phase boundary and becomes unstable. Besides, there is no minimum of χTMAO−D2O as TMAO concentration increases, indicating no stable stoichiometric TMAO−D2O compound or complex structures are present. The aggregate structures of PDEA can be schematically illustrated in Figure 7. Since χTMAO−D2O is negative, the solvent−solvent interaction is so strong that the solvent mixture becomes a poorer solvent for PDEA chains; therefore, part of the PDEA chains will form aggregates. While χPDEA−TMAO and χPDEA−D2O are positive, which indicates weaker polymer−solvent interactions. Meersman et al.37 using neutron scattering proved that the oxygen atom of TMAO can form strong hydrogen bonds with, on average, two or three water molecules while methyl groups have few interactions with water. The structure of the water hydrogen-bond network is little affected with the addition of TMAO38 because TMAO molecules can poorly fit into the hydrogen-bond network of water; they just exist as defects in the hydrogen-bond network of water and make the network tighter than in pure water.39,40 Since the TMAO−D2O interaction is very strong, active dissolution of PDEA chains by either TMAO or D2O becomes weaker. As a result, PDEA polymer chains tend to aggregate, as sketched in Figure 7. Hofmann et al.41 also studied Nisopropylacrylamide (NIPAM) and N,N-diethylacrylamide microgels in water/methanol mixture and found that the favored interaction of methanol and the amide proton of the NIPAM is the key to the co-nonsolvency phenomenon, which indicates that the active hydrogen atom can change the polymer−solvent and solvent−solvent interactions in a ternary

Figure 7. Cartoon of PDEA polymer chains forming aggregates for temperatures below the LCST. The size of polymers and solvent molecules in the cartoon is not their real size; they are magnified just for clarity.

system. All these imply that some preferred interaction can induce the co-nonsolvency effect. Our observation is akin to the phenomenon of interference of slow mode on liquid−liquid phase separation in polyelectrolyte solutions, although our system is uncharged.32 Whether the aggregates in the homogeneous phase can act as precursors before phase separation happens still needs further investigation in our future work.

4. CONCLUSIONS The coil-to-aggregate transition of PDEA polymer chains in TMAO/D2O solvent was studied by SANS and dynamic light scattering. It was found that the addition of TMAO decreases the LCST transition temperature of the PDEA solution. Although DLS results clearly show that aggregates can form in the homogeneous phase, SANS data show that the threecomponent system still obeys the mean-field theory after removing the low-q aggregate region. The ternary RPA is used to obtain three Flory−Huggins interaction parameters, i.e., χD2O−TMAO, χPDEA−TMAO, and χPDEA−D2O, which reveal that the strong solvent−solvent interaction may lead to the decrease of the LCST. Our study shed light on the molecular mechanism of phase transitions in ternary systems, such as the interference between aggregation and microphase separation.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b01502. Figures S1−S3 and Table S1 (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

*(H.C.) E-mail: [email protected]. *(C.C.H.) E-mail: [email protected]. F

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules ORCID

(14) Hammouda, B. Probing Nanoscale Structures-The SANS Toolbox, Chapter 54, http://www.ncnr.nist.gov/staff/hammouda/ the_sans_toolbox.pdf. (15) Reddy, P. M.; Taha, M.; Venkatesu, P.; Kumar, A.; Lee, M. J. Destruction of hydrogen bonds of poly(N-isopropylacrylamide) aqueous solution by trimethylamine N-oxide. J. Chem. Phys. 2012, 136, 234904. (16) Schroer, M. A.; Michalowsky, J.; Fischer, B.; Smiatek, J.; Grubel, G. Stabilizing effect of TMAO on globular PNIPAM states: preferential attraction induces preferential hydration. Phys. Chem. Chem. Phys. 2016, 18, 31459−31470. (17) Wang, T.; Liu, G.; Zhang, G.; Craig, V. S. J. Insights into Ion Specificity in Water−Methanol Mixtures via the Reentrant Behavior of Polymer. Langmuir 2012, 28, 1893−1899. (18) Wang, F.; Shi, Y.; Luo, S.; Chen, Y.; Zhao, J. Conformational Transition of Poly(N-isopropylacrylamide) Single Chains in Its Cononsolvency Process: A Study by Fluorescence Correlation Spectroscopy and Scaling Analysis. Macromolecules 2012, 45, 9196− 9204. (19) Chen, Q.; Kooij, E. S.; Sui, X.; Padberg, C. J.; Hempenius, M. A.; Schon, P. M.; Vancso, G. J. Collapse from the top: brushes of poly(N-isopropylacrylamide) in co-nonsolvent mixtures. Soft Matter 2014, 10, 3134−3142. (20) Scherzinger, C.; Schwarz, A.; Bardow, A.; Leonhard, K.; Richtering, W. Cononsolvency of poly-N-isopropyl acrylamide (PNIPAM): Microgels versus linear chains and macrogels. Curr. Opin. Colloid Interface Sci. 2014, 19, 84−94. (21) Jia, D.; Zuo, T.; Rogers, S.; Cheng, H.; Hammouda, B.; Han, C. C. Re-entrance of Poly(N,N-diethylacrylamide) in D2O/d-Ethanol Mixture at 27 °C. Macromolecules 2016, 49, 5152−5159. (22) Hore, M. J. A.; Hammouda, B.; Li, Y.; Cheng, H. CoNonsolvency of Poly(n-isopropylacrylamide) in Deuterated Water/ Ethanol Mixtures. Macromolecules 2013, 46, 7894−7901. (23) Pang, X.; Cui, S. Single-Chain Mechanics of Poly(N,Ndiethylacrylamide) and Poly(N-isopropylacrylamide): Comparative Study Reveals the Effect of Hydrogen Bond Donors. Langmuir 2013, 29, 12176−12182. (24) Flory, P. J.; Volkenstein, M. Statistical mechanics of chain molecules. Biopolymers 1969, 8, 699−700. (25) Yancey, P.; Clark, M.; Hand, S.; Bowlus, R.; Somero, G. Living with water stress: evolution of osmolyte systems. Science 1982, 217, 1214−1222. (26) Hashimoto, C.; Nagamoto, A.; Maruyama, T.; Kariyama, N.; Irisa, Y.; Ikehata, A.; Ozaki, Y. Hydration States of Poly(Nisopropylacrylamide) and Poly(N,N-diethylacrylamide) and Their Monomer Units in Aqueous Solutions with Lower Critical Solution Temperatures Studied by Infrared Spectroscopy. Macromolecules 2013, 46, 1041−1053. (27) Jia, D.; Yang, J. F.; Cheng, H.; Han, C. C. Basic Principle of SLS/DLS Measurements in Fluorescent/Phosphorescence Solutions. Acta Polym. Sin. 2015, 5, 564−570. (28) Jia, D.; Hollingsworth, J. V.; Zhou, Z.; Cheng, H.; Han, C. C. Coupling of gelation and glass transition in a biphasic colloidal mixture-from gel-to-defective gel-to-glass. Soft Matter 2015, 11, 8818− 8826. (29) Han, C. C.; Akcasu, A. Z. Fluctuations, Correlation, and Static/ Dynamic Scattering. In Scattering and Dynamics of Polymers; John Wiley & Sons (Asia) Pte Ltd: 2011; pp 27−102. (30) Hunger, J.; Ottosson, N.; Mazur, K.; Bonn, M.; Bakker, H. J. Water-mediated interactions between trimethylamine-N-oxide and urea. Phys. Chem. Chem. Phys. 2015, 17, 298−306. (31) Sinibaldi, R.; Casieri, C.; Melchionna, S.; Onori, G.; Segre, A. L.; Viel, S.; Mannina, L.; De Luca, F. The Role of Water Coordination in Binary Mixtures. A Study of Two Model Amphiphilic Molecules in Aqueous Solutions by Molecular Dynamics and NMR. J. Phys. Chem. B 2006, 110, 8885−8892. (32) Kanai, S.; Muthukumar, M. Phase separation kinetics of polyelectrolyte solutions. J. Chem. Phys. 2007, 127, 244908.

Murugappan Muthukumar: 0000-0001-7872-4883 He Cheng: 0000-0001-8718-4110 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The financial support from National Natural Scientific Foundation of China No. 21474119 and No. 21674020 is gratefully acknowledged. The identification of commercial products does not imply endorsement by the National Institute of Standards and Technology nor does it imply that these are the best for the purpose. This work is based upon activities supported in part by the US National Science Foundation under Grant DMR-1508249.

■

REFERENCES

(1) Mukherji, D.; Kremer, K. Coil−Globule−Coil Transition of PNIPAm in Aqueous Methanol: Coupling All-Atom Simulations to Semi-Grand Canonical Coarse-Grained Reservoir. Macromolecules 2013, 46, 9158−9163. (2) Fritsch, S.; Poblete, S.; Junghans, C.; Ciccotti, G.; Delle Site, L.; Kremer, K. Adaptive resolution molecular dynamics simulation through coupling to an internal particle reservoir. Phys. Rev. Lett. 2012, 108, 170602. (3) Mukherji, D.; Marques, C. M.; Kremer, K. Polymer collapse in miscible good solvents is a generic phenomenon driven by preferential adsorption. Nat. Commun. 2014, 5, 4882. (4) Tanaka, F.; Koga, T.; Winnik, F. M. Temperature-Responsive Polymers in Mixed Solvents: Competitive Hydrogen Bonds Cause Cononsolvency. Phys. Rev. Lett. 2008, 101, 028302. (5) Walter, J.; Sehrt, J.; Vrabec, J.; Hasse, H. Molecular Dynamics and Experimental Study of Conformation Change of Poly(N-isopropylacrylamide) Hydrogels in Mixtures of Water and Methanol. J. Phys. Chem. B 2012, 116, 5251−5259. (6) Kojima, H.; Tanaka, F.; Scherzinger, C.; Richtering, W. Temperature dependent phase behavior of PNIPAM microgels in mixed water/methanol solvents. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1100−1111. (7) Kyriakos, K.; Philipp, M.; Adelsberger, J.; Jaksch, S.; Berezkin, A. V.; Lugo, D. M.; Richtering, W.; Grillo, I.; Miasnikova, A.; Laschewsky, A.; Müller-Buschbaum, P.; Papadakis, C. M. Cononsolvency of Water/ Methanol Mixtures for PNIPAM and PS-b-PNIPAM: Pathway of Aggregate Formation Investigated Using Time-Resolved SANS. Macromolecules 2014, 47, 6867−6879. (8) Scherzinger, C.; Balaceanu, A.; Hofmann, C. H.; Schwarz, A.; Leonhard, K.; Pich, A.; Richtering, W. Cononsolvency of mono- and di-alkyl N-substituted poly(acrylamide)s and poly(vinyl caprolactam). Polymer 2015, 62, 50−59. (9) Hao, J.; Cheng, H.; Butler, P.; Zhang, L.; Han, C. C. Origin of cononsolvency, based on the structure of tetrahydrofuran-water mixture. J. Chem. Phys. 2010, 132, 154902. (10) Zhang, G.; Wu, C. The Water/Methanol Complexation Induced Reentrant Coil-to-Globule-to-Coil Transition of Individual Homopolymer Chains in Extremely Dilute Solution. J. Am. Chem. Soc. 2001, 123, 1376−1380. (11) Zhang, G.; Wu, C. Reentrant Coil-to-Globule-to-Coil Transition of a Single Linear Homopolymer Chain in a Water/Methanol Mixture. Phys. Rev. Lett. 2001, 86, 822−825. (12) Dudowicz, J.; Freed, K. F.; Douglas, J. F. Communication: Cosolvency and cononsolvency explained in terms of a Flory-Huggins type theory. J. Chem. Phys. 2015, 143, 131101. (13) Dudowicz, J.; Freed, K. F.; Douglas, J. F. Solvation of polymers as mutual association. II. Basic thermodynamic properties. J. Chem. Phys. 2013, 138, 164902. G

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules (33) Shibayama, M.; Tanaka, T.; Han, C. C. Small angle neutron scattering study on poly(N−isopropyl acrylamide) gels near their volume−phase transition temperature. J. Chem. Phys. 1992, 97, 6829− 6841. (34) Schild, H. G.; Muthukumar, M.; Tirrell, D. A. Cononsolvency in mixed aqueous solutions of poly(N-isopropylacrylamide). Macromolecules 1991, 24, 948−952. (35) Hiemenz, P. C.; Lodge, T. P. Polymer Chemistry; CRC Press: 2007. (36) Hammouda, B.; Ho, D.; Kline, S. SANS from Poly(ethylene oxide)/Water Systems. Macromolecules 2002, 35, 8578−8585. (37) Meersman, F.; Bowron, D.; Soper, A. K.; Koch, M. H. J. Counteraction of Urea by Trimethylamine N-Oxide Is Due to Direct Interaction. Biophys. J. 2009, 97, 2559−2566. (38) Laage, D.; Stirnemann, G.; Hynes, J. T. Why Water Reorientation Slows without Iceberg Formation around Hydrophobic Solutes. J. Phys. Chem. B 2009, 113, 2428−2435. (39) Munroe, K. L.; Magers, D. H.; Hammer, N. I. Raman Spectroscopic Signatures of Noncovalent Interactions Between Trimethylamine N-oxide (TMAO) and Water. J. Phys. Chem. B 2011, 115, 7699−7707. (40) Rezus, Y. L. A.; Bakker, H. J. Destabilization of the HydrogenBond Structure of Water by the Osmolyte Trimethylamine N-Oxide. J. Phys. Chem. B 2009, 113, 4038−4044. (41) Hofmann, C. H.; Plamper, F. A.; Scherzinger, C.; Hietala, S.; Richtering, W. Cononsolvency Revisited: Solvent Entrapment by NIsopropylacrylamide and N,N-Diethylacrylamide Microgels in Different Water/Methanol Mixtures. Macromolecules 2013, 46, 523−532.

H

DOI: 10.1021/acs.macromol.7b01502 Macromolecules XXXX, XXX, XXX−XXX