Polymer Phase Separation in Competition Solvents

Cononsolvency occurs if a mixture of two good solvents causes the collapse or demixing of polymers into a polymer-rich phase in a certain range of compositions of these two solvents. The better solvent is usually called cosolvent and another common solvent is called solvent. So far, the phase-transition mechanism behind cononsolvency is still rather controversially debated in literature. In this thesis, I experimentally investigated the cononsolvency effect of poly(N-isopropylacrylamide) (PNiPAAm) brushes with different grafting density in aqueous alcohol mixtures. I have used Vis-spectroscopic ellipsometry measurements and proved the hypothesis that the cononsolvency transition of PNiPAAm brushes consists of a volume phase-like equilibrium transition. I found a strong collapse transition in PNiPAAm brushes followed by a reentry behavior as observed by ellipsometry measurements. Using a series of alcohols with increasing alkyl-chain length I have demonstrated that the cononsolvency effect is enhanced and shifted to smaller volume fractions of the alcohol. Particularly for the alcohol with increasing hydrophobic property this is correlated with an increasing tendency of demixing between the cosolvent and water. This is apparently in contrast to the hypothesis of strongly associative solvents being the origin of the cononsolvency effect. The hypothesis of preferential adsorption, on the other hand, can account for this case by assuming an increasing hydrophobically driven adsorption of the cosolvent on the polymer chains. The recently proposed adsorption-attraction model based on the concept of preferential adsorption, can be used to predict the corresponding phase-transition behavior. In particularly the model predictions for variation of the grafting density is in agreement with the experimental findings. However, to reflect the imperfect mixing of the longer alcohols in water as well as finite miscibility of the polymers in the common solvent, extensions of the model have to be considered. I have shown that the simplest extension of the model taking into account the Flory-Huggins parameter for polymer and water can account for the qualitative changes observed for temperature changes in my experiments. Both a theoretical analysis and experimental observations show that the phase-transition mechanism of cononsolvency depends on the relative strengths of various interactions in the polymer solutions. A cononsolvency transition can be driven by a strong cosolvent-solvent attraction or by the preferential adsorption of cosolvent onto the polymer. By an extension of the adsorption-attraction model, I report on a comprehensive and quantitative theoretical study of the cononsolvency effect of neutral polymers such as PNiPAAm brushes, macro-gels and single long chains. The extended adsorption-attraction model is able to describe and predict the phase-transition behaviors of these systems in various aqueous alcohol solutions quantitatively. My analysis showed that besides the dominant role of polymer-cosolvent preferential adsorption and the monomer-cosolvent-monomer triple contacts (cosolvent-assisted temporary cross-linking effect) that define the strength of the collapse-transition in the cosolvent-poor region, other effects are shown to be of relevance: The non-ideal mixing between polymer and solvent plays a role in shifting the collapse transition to the lower-concentration region of cosolvent, and an increase of the demixing tendency between cosolvent and solvent on the polymer chains reduces the window width of the cononsolvency transition. Using data from my own experiments and literature I can show that the cononsolvency response of brushes, gels and single long polymer chain can be consistently described with the same model. The model parameters are consistent with their microscopic interpretation. In addition, weakening of the cononsolvency transition in cosolvent-poor aqueous solutions at high hydrostatic pressure can be explained by the suppression of demixing tendency between cosolvent and water, and between polymer and water in the case of PNiPAAm. An investigation of the grafting-density effect in the cononsolvency transition of grafted PNiPAAm polymer, showed that a decrease of grafting density at the collapse state as well as the temperature is fixed, the swollen polymer chains can show various morphologies not limited to collapse brush. In addition, my experimental results clearly showed that the strongest collapse state can be only realized by polymer brushes with moderate grafting densities. My results display the universal character of the cononsolvency effect with respect to series of cosolvents and show that PNiPAAm brushes display a well-defined and sharp collapse transition. This is most pronounced for 1-propanol as cosolvent which is still fully miscible in water. Potential applications are switches built from implementation of brushes in pores and similar concave geometries can be realized by harnessing the cononsolvency effect of stimuli-responsive polymers such as PNiPAAm. As an example of application of cononsolvency effect of grafted polymers, different molecular-weight PNiPAAm polymers are grafted around the rim of solid-state nanopores by using grafting-to method. I demonstrate that small amounts of ethanol admixed to an aqueous solution can trigger the translocation of fluorescence DNA through polymer-decorated nanopores. I can identify the cononsolvency effect as being responsible for this observation which causes an abrupt collapse of the brush by increasing the alcohol content of the aqueous solution followed by a reswelling at higher alcohol concentration. For the first time, I provide a quantitative method to estimate hydrodynamic thickness of a polymer layer which is grafted around the rim of nanopores. Regardless of the grafting density of a grafted PNiPAAm polymer layer around the rim of nanopores, in the alcohol-tris buffer mixtures, the polymer layer displays solvent-composition responsive behaviors in the range of metabolic pH values and room temperatures. Although in this study PNiPAAm was chosen as a model synthetic polymer, I believe in that the conclusions made for PNiPAAm can be also in general extended to other synthetic polymers as well as to biopolymers such as proteins. As a proof of concept of using synthetic polymers to mimic biological functions of cell-membrane channels, my study clearly transpired that cononsolvency effect of polymers can be used as a trigger to change the size of nanopores in analogy to the opening and closure of the gates of cell-membrane channels.:Chapter 1 Background and motivation 4 1.1 Liquid-liquid phase separation 4 1.2 Polymer phase separation in a pure solvent 5 1.3 Polymer phase separation in mixtures of two good solvents 10 1.4 Characterizing cononsolvency transition in experimental study 14 1.5 Research motivation 16 Chapter 2 Phase behaviors of PNiPAAm brushes in alcohol/water mixtures: A combined experimental and theoretical study 17 2.1 Introduction 17 2.2 Materials and Methods 17 2.2.1 Materials 17 2.2.2 Preparation of Polymer Brushes 18 2.2.3 VIS-Spectroscopic Ellipsometry Measurement 18 2.2.4 Determining a polymer brush’s overlap grafting density 19 2.2.5 Test of PNiPAAm solubility in short-chain polyols 20 2.3 The adsorption-attraction model 20 2.4 Equilibrium behavior of cononsolvency transition of PNiPAAm brushes 22 2.5 Role of volume of solvent molecules in the swelling of PNiPAAm brushes 24 2.6 Cononsolvency transition of PNiPAAm brushes in aqueous solutions of a series of alcohol 24 2.7 Isomer effect of alcohol in the cononsolvency transition of PNiPAAm brushes 27 2.8 Role of alcohol-water interaction in the cononsolvency transition of PNiPAAm polymers 28 2.9 Temperature effect in the cononsolvency transition of PNiPAAm brushes 30 2.10 Grafting-density effect in the cononsolvency transition of PNiPAAm brushes 33 2.11 Octopus-shape-micelle morphology of grafted PNiPAAm polymers 34 2.12 Chapter summary 35 2.13 Chapter appendix 37 2.13.1 Data extraction and reprocessing for the molar Gibbs free energy of mixing 37 2.13.2 Temperature effect in the cononsolvency transition of PNiPAAm gels 37 Chapter 3 The extended adsorption-attraction model 41 3.1 Introduction 41 3.2 An extension of the adsorption-attraction model 43 3.3 Numerical solution of the extended adsorption-attraction model 47 3.4 Validation of the extended adsorption-attraction model 50 3.4.1 Cononsolvency transition of polymer brushes and macro-gels in different alcohol-water mixtures 51 3.4.2 An analysis of the enthalpic interaction between cosolvent and solvent 57 3.4.3 The window width of the cononsolvency transition 60 3.4.4 Pressure effect in the cononsolvency transition of PNiPAAm polymers 61 3.4.5 Cononsolvency transition of a single long polymer 65 3.5 Chapter summary 66 3.6 Chapter appendix 67 3.6.1 Chemical potential change of mixing two components 67 3.6.2 The Enthalpic Wilson model 68 3.6.3 Estimation of effective Flory-interaction parameter 73 3.6.4 Crosslink-density effect in the cononsolvency transition of poly(N-isopropylacrylamide) micro-gel and macro-gel 74 3.6.5 Pressure effect on the dimensionless chemical potential change (μ) 75 3.6.6 Pressure effect on the cosolvent-solvent interaction (χcs) 76 3.6.7 Pressure effect on the polymer-solvent interaction (χps) 77 3.6.8 Chemical potential change of DMSO/water mixtures 78 Chapter 4 Gating the translocation of DNA through poly(N-isopropylacrylamide) decorated nanopores using the cononsolvency effect in aqueous environments 80 4.1 Introduction 80 4.2 Methods 80 4.2.1 Preparation of polymer-grafted gold membrane 80 4.2.2 Translocation experiments of fluorescence λ-DNA through nanopores 82 4.2.3 Method of identification and counting of DNA translocation events 84 4.3 Results and discussion 86 4.3.1 Grafting density effect on the swollen behaviors of PNiPAAm polymers around the rim of nanopores 86 4.3.2 Switching effect of polymer chains around the rim of nanopores in the tri-buffer/ethanol mixtures 88 4.3.3 Switching effect of polymer brushes on the flat surface in the tri-buffer/ethanol mixtures 92 4.3.4 An attempt of numerical fit of experimental data using the extended adsorption-attraction model 94 4.4 Chapter summary 95 4.5 Chapter appendix 96 4.5.1 An estimation of grafting density 96 4.5.2 The method of processing data 97 Chapter 5 Concluding remarks and outlooks 100 5.1 Concluding remarks 100 5.2 Outlooks: A preliminary discussion of the cononsolvency transition of polymer solutions 102 References and notes 108 List of figures 119 List of tables 128 Acknowledgements 130 List of publications 131 Erklärung 13

Hydrogen bonds in blends of poly(N-isopropylacrylamide), poly(n-ethylacrylamide) homopolymers, and carboxymethyl cellulose

Recently, it was reported that the physical crosslinking exhibited by some biopolymers could provide multiple benefits to biomedical applications. In particular, grafting thermoresponsive polymers onto biopolymers may enhance the degradability or offer other features, as thermothickening behavior. Thus, different interactions will affect the different hydrogen bonds and interactions from the physical crosslinking of carboxymethyl cellulose, the lower critical solution temperatures (LCSTs), and the presence of the ions. This work focuses on the study of blends composed of poly(N-isopropylacrylamide), poly(N-ethylacrylamide), and carboxymethyl cellulose in water and water/methanol. The molecular features, thermoresponsive behavior, and gelation phenomena are deeply studied. The ratio defined by both homopolymers will alter the final properties and the gelation of the final structures, showing that the presence of the hydrophilic groups modifies the number and contributions of the diverse hydrogen bonds.The authors want to acknowledge the funding obtained from the National Science Foundation of China (21574086), Shenzhen Fundamental Research Funds (No. KC2014ZDZJ0001A), Shenzhen Sci & Tech research grant (ZDSYS201507141105130), and China Postdoctoral Science Foundation Grant (2018M633119)

Manipulating Thermoresponsive Properties of Polycations in Water

This thesis reports the design and study of new series of thermoresponsive polycations with upper critical solution temperature (UCST) and lower critical solution temperature (LCST) type phase separation properties in water. The polymers were synthesized using reversible addition-fragmentation transfer polymerization process in presence of azobisisobutyronitrile (AIBN) as an initiator and 2-cyano-2-propylbenzoditionate (2-c-2-PBDT) as a chain transfer agent. Various solution properties of obtained polymers were studied. Transmittance measurements were utilized to determine the cloud point temperatures of poly[(4-vinylbenzyl)triethyl]ammonium chloride (P-VB-NEt3-Cl), poly[(4-vinylbenzyl)tripropyl]ammonium chloride (P-VB-NPr3-Cl), poly[(4-vinylbenzyl)tributyl]ammonium chloride (P-VB-NBu3-Cl) and poly[(4-vinylbenzyl)tripentyl]ammonium chloride (P-VB-NPen3-Cl) with several counterions (bis(trifluoromethane) sulfonimide, trifluoromethanesulfonate, CH3(CH2)4SO3 and CH3(CH2)11SO3) and anions belonging to Hofmeister series (Cl, NO3, SCN, H2PO4, SO4). P-VB-NEt3-Cl and P-VB-NPr3-Cl demonstrate both UCST and LCST type phase separation behavior depending on the chosen additive, whereas P-VB-NBu3-Cl and P-VB-NPen3-Cl only show LCST type phase transitions independent of the chosen anions. The phase transition temperature could be manipulated by varying the salt concentration of the polymer solutions; increasing the ionic strength causes the appearance of distinguishable transition in systems with no transition at low ionic strength. Combination of different anions in the system causes either increase or decrease of the cloud point temperature. The reversibility of the aforementioned transitions was studied and irreversibility of the transitions of polymer solutions with some anions was determined. Differential scanning calorimetry measurements were conducted to determine the enthalpy of heating of P-VB-NBu3-Cl and P-VB-NPen3-Cl with specific concentrations of counterions. Cononsolvency behaviour of P-VB-NBu3-Cl in water/DMF mixtures was studied, indicating that the turbidity occurs due to addition of either of solvents and remains regardless of temperature variation. Particle size measurements were conducted to explain the formation and behavior of particles depending on the temperature variation for P-VB-NBu3-Cl solutions with counterions

Polymer collapse in miscible good solvents is a generic phenomenon driven by preferential adsorption

Water and alcohol, such as methanol or ethanol, are miscible and, individually, good solvents for poly(N-isopropylacrylamide) (PNIPAm), but this polymer precipitates in water–alcohol mixtures. The intriguing behaviour of solvent mixtures that cannot dissolve a given polymer or a given protein, while the same macromolecule dissolves well in each of the cosolvents, is called cononsolvency. It is a widespread phenomenon, relevant for many formulation steps in the physicochemical and pharmaceutical industry, that is usually explained by invoking specific chemical details of the mixtures: as such, it has so far eluded any generic explanation. Here, by using a combination of simulations and theory, we present a simple and universal treatment that requires only the preferential interaction of one of the cosolvents with the polymer. The results show striking quantitative agreement with experiments and chemically specific simulations, opening a new perspective towards an operational understanding of macromolecular solubility

Equilibrium Swelling of Thermo-Responsive Gels in Mixtures of Solvents

Thermo-responsive (TR) gels of the LCST (lower critical solution temperature) type swell in water at temperatures below their volume phase transition temperature Tc and collapse above the critical temperature. When water is partially replaced with an organic liquid, these materials demonstrate three different types of equilibrium solvent uptake diagrams at temperatures below, above, in the close vicinity of Tc. A model is developed for equilibrium swelling of TR gels in binary mixtures of solvents. It takes into account three types of phase transitions in TR gels driven by (i) aggregation of hydrophobic side groups into clusters from which solvent molecules are expelled, (ii) replacement of water with cosolvent molecules in cage-like structures surrounding these groups, and (iii) replacement of water with cosolvent as the main element of hydration shells around backbone chains. The model involves a relatively small number of material constants that are found by matching observations on covalently cross-linked poly(N-isopropylacrylamide) macroscopic gels and microgels. Good agreement is demonstrated between the experimental data and results of numerical analysis. Classification is provided of the phase transition points on equilibrium swelling diagrams

The evolution of bicontinuous polymeric nanospheres in aqueous solution

Complex polymeric nanospheres in aqueous solution are desirable for their promising potential in encapsulation and templating applications. Understanding how they evolve in solution enables better control of the final structures. By unifying insights from cryoTEM and small angle X-ray scattering (SAXS), we present a mechanism for the development of bicontinuous polymeric nanospheres (BPNs) in aqueous solution from a semi-crystalline comb-like block copolymer that possesses temperature-responsive functionality. During the initial stages of water addition to THF solutions of the copolymer the aggregates are predominantly vesicles; but above a water content of 53% irregular aggregates of phase separated material appear, often microns in diameter and of indeterminate shape. We also observe a cononsolvency regime for the copolymer in THF–water mixtures from 22 to 36%. The structured large aggregates gradually decrease in size throughout dialysis, and the BPNs only appear upon cooling the fully aqueous dispersions from 35 °C to 5 °C. Thus, the final BPNs are ultimately the result of a reversible temperature-induced morphological transition

Cononsolvency of the responsive polymer poly(N-isopropylacrylamide) in water/methanol mixtures: a dynamic light scattering study of the effect of pressure on the collective dynamics

The collective dynamics of 25 wt% poly(N-isopropylacrylamide) (PNIPAM) solutions in water or an 80:20 v/v water/methanol mixture are investigated in the one-phase region in dependence on pressure and temperature using dynamic light scattering. Throughout, two dynamic modes are observed, the fast one corresponding to the relaxation of the chain segments within the polymer blobs and the slow one to the relaxation of the blobs. A pressure scan in the one-phase region on an aqueous solution at 34.0 °C, i.e., slightly below the maximum of the coexistence line, reveals that the dynamic correlation length of the fast mode increases when the left and the right branch of the coexistence line are approached. Thus, the chains are rather swollen far away from the coexistence line, but contracted near the phase transition. Temperature scans of solutions in neat H2O or in H2O/CD3OD at 0.1, 130, and 200 MPa reveal that the dynamic correlation length of the fast mode shows critical behavior. However, the critical exponents are significantly larger than the value predicted by mean-field theory for the static correlation length, ν = 0.5, and the exponent is significantly larger for the solution in the H2O/CD3OD mixture than in neat H2O

Cononsolvency of the responsive polymer poly(N-isopropylacrylamide) in water/methanol mixtures: a dynamic light scattering study of the effect of pressure on the collective dynamics

The collective dynamics of 25 wt% poly(N-isopropylacrylamide) (PNIPAM) solutions in water or an 80:20 v/v water/methanol mixture are investigated in the one-phase region in dependence on pressure and temperature using dynamic light scattering. Throughout, two dynamic modes are observed, the fast one corresponding to the relaxation of the chain segments within the polymer blobs and the slow one to the relaxation of the blobs. A pressure scan in the one-phase region on an aqueous solution at 34.0 °C, i.e., slightly below the maximum of the coexistence line, reveals that the dynamic correlation length of the fast mode increases when the left and the right branch of the coexistence line are approached. Thus, the chains are rather swollen far away from the coexistence line, but contracted near the phase transition. Temperature scans of solutions in neat H2O or in H2O/CD3OD at 0.1, 130, and 200 MPa reveal that the dynamic correlation length of the fast mode shows critical behavior. However, the critical exponents are significantly larger than the value predicted by mean-field theory for the static correlation length, ν = 0.5, and the exponent is significantly larger for the solution in the H2O/CD3OD mixture than in neat H2O

The reentrant condensation of polyelectrolytes induced by diluted multivalent salts: A mean-field level revisiting

We study the reentrant condensation of polyelectrolytes in dilute solutions of small multivalent salts, whose phase-transition mechanism remains poorly understood. Motivated by recent full atomic simulation results reported by the Caltech group on phase behaviors of polyelectrolytes in presence of multivalent salts (DOIs: 10.1021/acs.macromol.3c02437 and 10.1021/acs.langmuir.3c03640), in this work we construct a simple but effective mean-field model which can rationalize the essential features of the reentrant condensation including the phase diagram of polyelectrolyte. The model unveils that the strong adsorption between the ionic monomers and multivalent ions can be at the origin of the peculiar phenomenon that rather low concentrations of multivalent salts trigger both collapse and re-entry transitions. For the first time, the analytical solution of the model indicates that a minimum of coupling energy due to sharing multivalent salt ions between ionic monomers is essential for a phase transition to occur, which can explain the enigmatic observation that polyelectrolytes can only show phase transition in a dilute solution of salts with selective multivalency. Our analytical calculations also show that the incompatibility of the uncharged moieties of the polyelectrolytes with water is critical to regulate phase behaviors of polyelectrolytes in aqueous solutions. This is in agreement with recent experimental investigations on solution properties of amphiphilic proteins. The obtained results will contribute to the understanding of liquid-liquid phase separation in biological systems where multivalent ions bound to bio-polyelectrolytes play an essential role.Comment: 37 pages, 11 figure