Temperature-responsive polymer

Thermoresponsive polymers are polymers that change their physical properties drastically and discontinuously with temperature. The term is most often used when the affected property is the solubility in a particular solvent, but need not be limited to it. Thermoresponsive polymers belong to the class of stimulus-responsive materials, in contrast to sensitive materials, which only continuously adapt their properties to the surrounding conditions.

Thermoresponsive polymers in the narrower sense have in their temperature-composition diagram of a miscibility gap. Depending on whether the miscibility gap occurs at high or low temperature, there is a lower or upper critical solution temperature ( engl. lower or upper critical solution temperature, LCST or UCST abbreviated ). After the common English abbreviation, the polymers in question are often referred to briefly as LCST or UCST polymers.

The focus of the research are mainly polymers having thermosensitivity in aqueous solution. As a promising application fields of tissue engineering, chromatography, drug delivery and bioseparation be seen. Commercial applications, there has been few. One example is the cell culture plates which are coated with an LCST polymer.

• 5.1 Cloud point ( engl. cloud point )
• 5.2 hysteresis
• 5.3 Further properties

• 6.1 thermosensitivity in organic solvents
• 6.2 thermosensitivity in water

The ball globules transition

Thermoresponsive polymers are in solution as an open-chain ball. In the phase separation temperature collapse these into compact globules (English -to- coil transition globules ). Through methods of static and dynamic light scattering, this process can be observed directly. Indirectly, the decrease in viscosity can be tracked. If there are no mechanisms in place to minimize the surface tension between globules and solvent, it comes to the aggregation of the globules, which initially ultimately manifests itself in the formation of visible particles in increasing turbidity of the solution and.

The phase diagram of thermoresponsive polymers

The phase separation temperature (and thus the cloud point ) is dependent on the polymer concentration. Therefore, temperature-composition diagram can be used to represent the thermoresponsive behavior over a wide concentration range. Phase separation takes place in a polymer-poor and polymer-rich phase. In strictly binary mixtures, the composition of the coexisting phases could be determined by forming the tie line (see critical solution temperature). Since polymers generally have a molecular weight distribution, this simple procedure is only partly applicable.

During the phase separation, it may happen that the polymer rich phase solidifies like glass, before the equilibrium state has been reached. This is dependent on the glass transition temperature of the particular composition of the mixture. It is convenient to represent the development of the glass transition temperatures in the phase diagram, even though it is not a state of equilibrium. The intersection point between the glass curve and cloud point curve is called Berghmans point. In the case of above the UCST polymer Berghmans point phase separation is carried out in two liquid phases, under a liquid polymer-poor phase and a polymer-rich phase became glassy. For LCST polymers, the inverse behavior is observed.

Thermodynamics

Polymers dissolve in a solvent, if doing so reduces the Gibbs free energy of the system, ie the change in the Gibbs free energy (? g ) is negative. From the known Legendre transform of the Gibbs - Helmholtz equation shows that the enthalpy of mixing from? G ( AH ) and entropy of mixing (? S ) is composed.

If no interactions between the participating materials exist, so no enthalpy of mixing would be present and the entropy of mixing would be ideal. The ideal entropy of mixing of several pure substances is always positive ( the term T ∙? S then negative) and? G would be negative at any mixing ratio. It would be given complete miscibility. It follows that gaps mixture must be explained by interaction between the components. In the case of a polymer solution, polymer - polymer, solvent, solvent, and polymer -solvent interactions must be taken into account. A phenomenological model for the description of polymer phase diagrams was developed by Flory and Huggins (see Flory -Huggins theory). The resulting expression for the change in the Gibbs free energy is based on an adapted for polymers term for the ideal entropy of mixing and interaction parameter, which describes the sum of all interactions.

With

• R = universal gas constant
• M = number of occupied lattice positions per molecule ( for the polymer solutions m1 approximate the degree of polymerization and m 2 = 1)
• φ is the volume fraction of the polymer and of the solvent
• χ = interaction parameter

From the Flory -Huggins theory follows, for example, that the UCST (if any) increases with increasing molecular weight and a simultaneous shift in the solvent-rich zone. Whether a polymer having an LCST and / or UCST behavior, can be calculated from the temperature dependence of the interaction parameter can be derived ( see figure). It should be noted that the interaction parameter contains not only enthalpic elements, but also the non-ideal entropy of mixing (eg the very strong hydrophobic effect in aqueous solution). Since the interaction parameter contains both enthalpic and entropic also elements which in turn are composed of many components, the classical Flory -Huggins theory is difficult to draw conclusions about the molecular cause of miscibility gaps.

Applications

Bioseparation

Thermoresponsive polymer can be provided with functional groups which specifically bind to certain biomolecules. These biomolecules can then be precipitated by a slight change in temperature along with the polymer. Isolation is possible by filtration or centrifugation.

Thermoresponsive surfaces in tissue engineering and chromatography

For some polymers could be demonstrated that thermoresponsive behavior on surfaces can be transferred. For this purpose, the surface, the polymer chains are covalently bonded to the surface either with a polymer film or coating. The wetting of the surface with the solvent can be controlled by small changes in temperature. This behavior can be exploited, for example in tissue engineering, because the adhesion of cells to surfaces depends strongly on the hydrophilicity / hydrophobicity of the surface. Thus it is possible, cells detach without the usual application of enzymes, by a small temperature change of a corresponding coated cell culture plate. Corresponding products are already commercially available.

Also explored is the use of thermoresponsive polymers as stationary phase in liquid chromatography. The polarity of the stationary phase can here be extremely affected by a temperature change, so that the separation efficiency for different classes of compounds can be varied without changing columns.

Thermoresponsive gels

Three-dimensional polymer networks are insoluble in all solvents, they may have only a swelling. Thermoresponsive polymers show a discontinuous course of the degree of swelling with temperature. In the volume phase transition temperature (german volume phase transition temperature, VPTT ) enters a strong change in the degree of swelling. Numerous research try this behavior for the temperature-induced drug release to use, as previously can diffuse easily embedded agents in the swollen state of gel.

Characterization of thermoresponsive polymer solutions

Cloud point ( engl. cloud point )

Experimentally, the phase separation can be easily examined by Turbidimitrie. There is no procedure for determining the cloud point, which is equally appropriate for all systems. Therefore, no standard definition exists. It is often defined as the temperature at which turbidity is first to detect ( the onset ) and the temperature at the inflection point of the transmission curve or the temperature at a defined transmission ( for example, 50 %). Also undefined is the name for the temperature during re aware of the solution, since the term clearing point is already used for phase transitions in liquid crystals.

Hysteresis

The cloud points (or " clearing points " ) on cooling and heating of a thermoresponsive polymer solution are not identical, because the equilibration takes time. The temperature interval between the cloud points in cooling and heating phase is called hysteresis. The cloud points are dependent on the cooling or heating rate used and the hysteresis is reduced with decreasing rates. It is thought that the hysteresis is a function of the temperature, viscosity, glass transition temperature and the ability to form additional intra-and inter-molecular bonds in phasenseparatierten state.

Other properties

It is of very great importance for potential applications, how much the polymer content of the two phases after separation differs. For most applications, a phase separation into pure solvent and pure polymer is desirable, but this is not practically possible. The course of the phase separation will depend on the exact shape of the phase diagram.

Example: The phase diagram of a solution of polystyrene (molecular weight 43,600 g / mol) can be derived in the solvent cyclohexane, that at a total polymer concentration of 10% upon cooling from 25 to 20 ° C, a polymer-poor phase with about 1 % polymer and a polymer-rich phase is formed with about 30 % polymer.

Also desirable for many applications is a sharp phase transition, which manifests itself in an abrupt drop of the transmission curve. The sharpness of the phase transition is related to the strength of the phase separation, but is additionally influenced whether all present in the blend polymer chains have the same cloud point. This is dependent on the polymer end, the dispersity and possibly of varying copolymer compositions countries.

Examples of thermoresponsive polymers

Thermosensitivity in organic solvents

Due to the low entropy of mixing occur miscibility gaps in polymer solutions on relatively common. There are known a large number of polymers which exhibit in organic solvents UCST and / or LCST behavior. As examples of organic polymer solutions with UCST polystyrene in cyclohexane, polyethylene may be mentioned in diphenyl ether or polymethyl methacrylate in acetonitrile. A LCST can be found, for example, the systems polypropylene in n- hexane, polystyrene or polymethylmethacrylate in butyl acetate in 2- propanone.

Thermosensitivity in water

Polymer solutions, which show thermosensitivity in water are of particular importance, since the solvent water is cheap, safe and biologically relevant. In science is tried for some time to make water-soluble thermoresponsive polymers for drug release or intelligent materials in tissue engineering available. Many polymers with LCST in water are known. Is best studied poly (N- isopropylacrylamide). Other examples include hydroxypropyl cellulose, poly ( vinyl caprolactam) and polyvinyl methyl ether.

A number of large engineered polymers show next LCST and UCST behavior in water. However, the UCST is usually in temperature ranges outside the 0-100 - ° C spectrum and thus can be detected only under extreme test conditions. Examples are polyethylene, polyvinyl methyl ether and polyhydroxyethylmethacrylate. There are also examples of polymers having UCST behavior is in the range between 0 and 100 ° C. There are, however, large differences in ionic strength, can be observed in the UCST behavior. Some polyzwitterions show UCST behavior in pure water, but not in saline water. Polyacrylic acid, however, shows UCST behavior only at high ionic strengths. Examples of polymers that may exhibit UCST behavior both in pure water as well as under physiological conditions, are poly (N- acrylglycinamid ), urea -functionalized polymers and copolymers of acrylamide and acrylonitrile. However, applies to the determination of cloud points in pure water, the polymers must not contain ionic groups.

In the examples referred to is to be noted that the UCST is dependent on the molecular weight of the polymers. At the LCST, this is not necessarily the case, as shown for poly ( N-isopropylacrylamide).