Poly(cyclic imino ether)s : from chiral poly(2-oxazoline)s to thermo-responsive polymers

Poly(cyclic imino ether)s: From chiral poly(2-oxazoline)s to thermo-responsive polymers In nature, most polymers are chiral and form a defined secondary structure like helices or sheets. However, synthetic chiral polymers that form such secondary structures are less common. 2-Oxazolines can be polymerized via a living cationic ring-opening polymerization process. Since this monomer can become chiral when the 4th or 5th position is substituted, the goal of this research was to evaluate whether polymerization of such monomers yield chiral polymers that form secondary structures. Chapter 2 describes the synthesis and living polymerization of chiral 2-butyl-4-ethyl-2-oxazolines (BuEtOx) under microwave-assisted conditions to decrease the polymerization time and to optimize the polymerization process. The difference in solution properties between the racemic and the enantiopure polymers was investigated by solubility tests, optical rotation, circular dichroism (CD) and small angle neutron scattering (SANS) measurements. The combined results revealed that the racemic poly-RS-2-butyl-4-ethyl-2-oxazoline (p-RS-BuEtOx) is optically inactive and forms a random coil in solution making the polymer soluble in most organic solvents while the enantiopure p-R-BuEtOx and p-S-BuEtOx are only soluble in a small range of solvents. The enantiopure polymers are optically active and form a flexible structure that fluctuates around an ordered secondary structure with only a part of the monomeric units in an ordered conformation at the same time like observed for natural polyproline II type helices. The solid state properties of the polymers were studied by differential scanning calorimetry (DSC), x-ray diffraction (XRD) and CD measurements of polymer films revealing that the enantiopure polymers form chiral crystalline structures while the racemic polymer is completely amorphous. How the alkyl side-chain length on the 2-position of the chiral monomer influences the polymer properties was investigated in Chapter 3. P-R-2-ethyl-4-ethyl-2-oxazoline (p-R-EtEtOx) and poly-R-2-octyl-4-ethyl-2-oxazoline (p-R-OctEtOx) have approximately the same optical properties in solution as p-R-BuEtOx; however, when the side-chain length is increased further to nonyl-chains the secondary structure measured by CD changed significantly in the solid state. P-R-EtEtOx was completely amorphous while poly-R-2-nonyl-4-ethyl-2-oxazoline (p-R-NonEtOx), p-R-OctEtOx and poly-R-2-undecyl-4-ethyl-2-oxazoline (p-R-UndeEtOx) are semi-crystalline like p-R-BuEtOx, although with a much lower melting temperature. The crystals formed were found to be chirally ordered. The thermal properties and the CD results suggest that main-chain crystallization occurs in p-R-BuEtOx, while only side-chain crystallization takes place in the chiral polymers with longer alkyl side-chains. In the first part of Chapter 4 the presence of the majority rule effect is investigated by copolymerizing R-BuEtOx with S-BuEtOx in different ratios. Optical rotation and CD measurements of the copolymers revealed that the chiral polymer is not rigid enough to force the enantiomer that is in the minority to rotate in the same direction as the major enantiomer. Nonetheless, the thermal properties of these copolymers could be controlled by the ratio of the monomers. In the second part of Chapter 4 amphiphilic statistical and block copolymers are discussed based on the hydrophilic 2-etyl-2-oxazoline (EtOx) and the hydrophobic chiral R-BuEtOx or racemic RS-BuEtOx. The statistical copolymerization resulted in the formation of a gradient copolymer where the monomer composition gradually changed from EtOx rich to pure BuEtOx. These gradient copolymers as well as block copolymers with different block ratios self-assembled into water as determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). It was found that the type of structure formed depends on whether the racemic block or the enantiopure block is used and on the R-BuEtOx to EtOx ratio. Besides chiral poly(2-oxazoline)s also a new thermo-responsive poly(2-oxazoline), namely poly-2-cyclopropyl-2-oxazoline was developed which revealed a significantly faster polymerization rate compared to other 2-oxazolines and a thermal response in aqueous solution at a slightly higher temperature compared to poly-2-n-propyl-2-oxazoline measured by turbidity measurements, viscometry and DLS. The obtained polymer is amorphous with a glass transition temperature (Tg) of 80 °C, desirable for potential biomedical applications. The influence of a series of Hofmeister salts was investigated on the cloud point temperatures of various thermo-responsive poly(2-oxazoline)s using turbidimetry. The ionic response decreased with the decrease in hydrohilicity of the poly(2-oxazoline). Furthermore, the influence of the monomer ring-size on the thermal response of the polymers was investigated by synthesizing and polymerizing a series of 2-oxazines. The obtained polymers have a lower cloud point temperature compared to the corresponding poly(2-oxazoline)s. The alkyl side-chain length had a stronger influence on the cloud point temperature than the number of methylene units in the backbone. These thermo-responsive polymers are described in Chapter 5. In general it can be concluded that the enantiopure polymers are chirally ordered and form a more compact structure compared to the racemic polymer. Copolymerizing the enantiopure monomer with a hydrophilic comonomer results in amphiphilic self-assembled structures in water, which might be useful for separating enantiomeric mixtures in aqueous solution or for drug delivery applications. Furthermore, the synthesized thermo-responsive poly(2-oxazoline)s and poly(2-oxazine)s will be potentially interesting building blocks for applications requiring easy control over the cloud point temperature. Due to the amorphous nature and desirable high Tg of poly(2-cyclopropyl-2-oxazoline), this polymer has a significant potential as material for biomedical applications

Main-chain chiral poly(2-oxazoline)s:Influence of alkyl side-chain on secondary structure formation in the solid state

\u3cp\u3eThe influence of the side-chains of main-chain chiral poly(2-oxazoline) s on their thermal properties was investigated using differential scanning calorimetry (DSC) and the nature of the obtained melting endotherms was further investigated by thermal annealing of the polymers. Poly(R-2-ethyl-4-ethyl-2-oxazoline) (p-R-EtEtOx) was found to be amorphous, while polymers with longer side-chains are semicrystalline. Previously we reported that the chirally ordered crystals of poly(R-2-butyl-4-ethyl-2-oxazoline) (p-R-BuEtOx) have a high melting temperature of more than 200°C. in this work we demonstrate that elongation of the side-chains frombutyl to octyl results in a decrease in the crystallization rate and melting temperature suggesting that the chirally ordered crystals of p-R-BuEtOx are based on close packing of the mainchain enhancing diploar interactions between the tertiary amide moieties. Crystallizaiton of chiral polymers with longer side-chains resultsmay then be driven by close packing of the side-chains. This is supported by the observation that further elongation of the sidechain length increases the crystallization rate. Moerover, an additional melting endothermappears for thesepolymers at a lower temperature upon annealing ascribed to a dual crystal size population. Circular dichroism (CD) measurements of the semicrystalline main-chain chiral polymer films revealed the presence of chirally ordered crystals while X-ray diffraction (XRD) patterns revealed a closer packing of the chiral poly(2-alkyl-2-oxazoline) s compared to the non-chiral polymers, suggested to result form the chiral ordering in the crystals. Grazing incidence wide angle x-ray scattering (GIWAXS) patterns indicated that the chiral crystals of p-R-BuEtOx do not form a helical structure, however, the substrate does influence the type of structure formed.\u3c/p\u3

Microwave-assisted cationic ring-opening polymerization of 2-oxazolines

More than any other polymer class, the synthesis of (co-) poly (2-oxazoline) s has benefited tremendously from the introduction of microwave reactors into chemical laboratories. This review focuses on research activities in the area of (co-) poly(2-oxazoline) s prepared by microwave-assisted syntheses and summarizes the current state-of-the-art for microwave-assisted syntheses of 2-oxazoline monomers, microwave-assisted ring-opening (co-)polymerizations of 2-oxazolines, and prominent examples of post-polymerization modifications of (co-)poly(2-oxazoline) s. Special attention is paid to kinetic analyses of the microwave-assisted polymerization of 2-oxazolines and to the discussion of non-thermal microwave effects