Synthesis, characterization and applications of quadruple hydrogen bonded polymers

The field of supramolecular polymer chemistry has expanded rapidly since the development of the first supramolecular polymers by Jean-Marie Lehn and coworkers in 1990. Inspired by the intriguing new properties of this new class of polymers, many researchers explored the potential of supramolecular polymers based on various non-covalent interactions. Arrays of multiple hydrogen bonds are currently one of the most widely applied non-covalent interactions in supramolecular chemistry and supramolecular polymers due to their high directionality and strength. In Chapter 1 a literature overview on multiple hydrogen bonded supramolecular polymers is given. The translation from chemical structure to bulk material properties appears to be dominated by the presence of additional interactions and phase separation, which results in a change of polymerization mechanism from isodesmic to cooperative. For the 2-ureido-pyrimidinone (UPy) telechelic polymers developed in our group, the presence of lateral hydrogen bonding moieties is known to result in phase separated nano-fibrillar crystallites. The macroscopic properties of the bulk material are highly depending on the presence and stability of these nano-fibers. To evaluate the applicability and processeability of UPy functionalized poly(e-caprolactone) (PCl) polymers for potential use as biomaterials, the macroscopic properties of bis-(UPy-U)-poly(e-caprolactone) supramolecular polymers were investigated in Chapter 2. First, the reproducibility of the macroscopic properties was evaluated. The macroscopic properties vary from batch to batch, which is attributed to small differences in crystallinity of the PCl block at room temperature when cast from chloroform. Crystallization of the PCl block results in a higher Young’s modulus and a reduction of the ultimate tensile strength and maximum strain. The presence of small amounts of monofunctional impurities significantly influences the macroscopic properties of the materials. This illustrates the importance of full functionalization during synthesis. Ageing of the material resulted in changes of the macroscopic properties of the materials, which is attributed to an increase of the crystallinity of the PCl block in time. The material retains sufficient mechanical properties for the use at physiological temperature. Finally, the influence of processing conditions on the macroscopic properties was evaluated. Casting from hexafluoro-isopropanol HFIP resulted in materials with a higher Young’s modulus and a higher melting point of the UPy-urea nano-fibers compared to materials cast from chloroform. Significant degradation of the UPy moieties was observed above 135 °C, which implies that melt-processing is not feasible. The results show that many factors affect the macroscopic properties of bis-(UPy-U)-poly(e-caprolactone) supramolecular polymers. Therefore, care should be taken when characterizing the macroscopic properties of supramolecular polymers. The macroscopic properties of bis-(UPy-urea) supramolecular polymers were further investigated in Chapter 3 by changing the molecular structure or by the use of additives. The polymer backbone was changed from the semi-crystalline poly(e-caprolactone) (PCl) block to the amorphous poly(ethylene-butylene) (PEB) block. The PEB materials cast from chloroform show a remarkable resemblance with PCl materials cast from chloroform in which the PCl block is amorphous at room temperature. Since the urea lateral hydrogen bonding is known to be important for the nano-fiber formation, the linker between the UPy and urea moieties was changed from a flexible 1,6-hexyl spacer to a 1,4-trans-cyclohexyl spacer. The more rigid 1,4-trans-cyclohexyl spacer was expected to prearrange the urea moieties to result in better stacking and subsequent crystallization. However, the aggregates were found to be shorter and thinner according to AFM measurements and infrared measurements revealed weaker hydrogen bonding. The Young’s modulus is decreased significantly compared to the hexyl materials, revealing the importance of the long nano-fibers on the macroscopic properties of bis-(UPy-urea) materials. PCl and PEB polymers comprising anthracene-bisurea moieties were designed to be incorporated into the UPy-urea nano-fibers to act as covalent cross links between the nano-fibers. The PEB anthracene-bisurea additive revealed no significant changes in macroscopic properties when 10% of the anthracene-bisurea polymer was incorporated in the bis-(UPy-urea) material. Although it was not possible to enhance the mechanical properties of the materials by the approaches described here, the experiments show that it is possible to change the molecular structure of the bis-(UPy-urea) polymer without a loss of its macroscopic properties. Next to changing the polymer backbone and the spacer in between the UPy and urea moieties, also the effect of small variations of the UPy moiety were investigated. The influence of substituents at the 5- and 6-position of the UPy on the aggregation of bis-(UPy-urea)-poly(ethylene-butylene) polymers into nano-fibers is described in Chapter 4. Using a small library of polymers with various substituents, the aggregation pathway towards the UPy-urea nano-fibers was elucidated. A change in the substituents at the 5- or 6-position of the UPy strongly influences the aggregation and subsequent crystallization. Using a wide variety of techniques, the different stages in the aggregation pathway were assessed. The presence of a substituent at the 5-position was found to hamper the interaction between stacks and hence nano-fiber crystallization. This study demonstrates that minimal molecular changes can result in a large difference in aggregation behavior. The bis-UPy supramolecular polymers allow for a modular approach for the incorporation of bioactive moieties. In Chapter 5, an RNase S assay was developed to serve as a model system to evaluate the influence of processing parameters on the activity of the material. UPy-urea functionalized S-peptide was incorporated into a bis-(UPy-U)-poly(e-caprolactone) supramolecular polymer by casting from different solvents. The solvent strongly influences the anchoring of the UPy functionalized peptide into the material as detected by release experiments. Although significant release is observed, the materials remain active according to the RNase S assay. The results of the assay demonstrate a large influence of the solvent on the activity of the material. The developed RNase S assay was also applicable on materials electrospun from HFIP, which revealed that the materials remain active after electrospinning. The development of hydrogen bonding motifs with a high dimerization constant is an important step towards complex macromolecular structures based on multiple non-covalent interactions due to their high directionality. Therefore, the ureido-benzoic acid (UBA) self-complementary hydrogen bonding motif is introduced and characterized in Chapter 6. The motif shows a strong and self-complementary quadruple hydrogen bonding with a dimerization constant in the order of 109 M-1 in chloroform. A supramolecular UBA polymer showed a vast increase in mechanical properties compared to its unfunctionalized counterpart, revealing its applicability in supramolecular chemistry. The UBA motif displays orthogonal self-assembly with UPy molecules and the strong quadruple hydrogen bonding can be reversibly switched ‘off’ and ‘on’ by the addition of base and acid, respectively. One of the UBA molecules was designed to have the ability to hydrogen bond to NaPy molecules at high concentration. Upon dilution, the equilibrium is completely shifted from the UBA:NaPy heterodimer to the UBA homodimers. The orthogonal self-assembly, the reversible off- and on- switching using base and acid and the dilution induced deprotection of the UBA motif show the broad promise of this new self-complementary hydrogen bonding motif in supramolecular chemistry. In conclusion, the results in this thesis show the potential of quadruple hydrogen bonded supramolecular polymers. The introduction of the UPy group resulted in the development of supramolecular thermoplastic elastomers with good macroscopic properties, which allows for a wide variety of possible applications as exemplified in this thesis. Although the UPy hydrogen bonding motif as well as other hydrogen bonding motifs earned their marks in the field of supramolecular chemistry, the development of new hydrogen bonding motifs can nonetheless introduce new features that are crucial for the full exploitation of this exciting field. The advanced self-assembly properties of the UBA motif as described in the final chapter of this thesis can be a beginning of a wide variety of future applications in supramolecular chemistry and supramolecular polymers