Chirality in Supramolecular Polymers

Abstract

Whereas the role of cooperativity in various self-assembly processes observed in Nature (such as protein aggregation, protein folding and DNA hybridization) is widely recognized, the effect of cooperativity in synthetic supramolecular polymers has received little attention to date. This Thesis addresses the supramolecular polymerization mechanisms of synthetic self-assembled systems, with particular attention on the effect of cooperativity on the supramolecular polymerization process. The self-assembling chiral monomer, a benzene-1,3,5-tricarboxamide derivative, forms helical stacks as a result of intermolecular hydrogen bonding. Because the chirality in the monomer can be expressed at the supramolecular level, this system also allows us to study amplification of chirality in supramolecular polymers. In Chapter 1 an overview was given of supramolecular polymers that self-assemble by formation of hydrogen bonds. Special attention was paid to the mechanisms by which the supramolecular polymers self-assemble. Two general self-assembly mechanisms are recognized: the isodesmic and the cooperative mechanism. First the thermodynamic aspects of these mechanisms were presented, after which examples from literature of hydrogen-bonding driven supramolecular polymerizations were discussed. Finally, the phenomenon of amplification of chirality was introduced, which can be studied for a variety of systems, including supramolecular polymers. In Chapter 2 the supramolecular polymerization of a chiral and an achiral benzene-1,3,5-tricarboxamide monomer, as studied with temperature-dependent circular dichroism (CD) and UV-vis spectroscopy, was discussed. The self-assembly of these monomers was found to be highly cooperative and could be quantified by modeling the temperature-dependent absorption data. The origin of this cooperativity could be ascribed to electronic effects, as revealed by DFT calculations. Time-dependent two-component mixing experiments, revealed a fast exchange (on the time scale of seconds) between aggregates and monomers, indicative of the formation of a dynamic supramolecular polymer. The use of vibrational CD (VCD) spectroscopy as an additional technique to characterize the helical stacks of chiral benzene-1,3,5-tricarboxamide monomers was described in Chapter 3. This revealed that the amide groups in the assemblies are in a chiral (i.e. helical) organization and that the handedness of the helical stacks can be related to the stereoconfiguration of the side chains present in the monomer. In Chapter 4 the synthesis of an N-alkylated benzene-1,3,5-tricarboxamide derivative that was designed to act as a chain stopper in the cooperative self-assembly of the benzene-1,3,5-tricarboxamide monomers, was presented. The modification of the molecular structure reduced the efficiency of the chain stopper to such a degree that it only worked effectively at high concentrations. This is most likely the result of an anti-parallel arrangement of the amide groups in the chain stopper molecule, as was concluded from DFT calculations. This demonstrated that for electronically coupled monomers, the design of a chain stopper is not trivial, as modification at one side of the molecule can affect the binding strength of the other side of the molecule. A description of a study of chiral amplification of symmetrical benzene-1,3,5-tricarboxamide monomers, which is facilitated by the dynamic nature of the assemblies, was presented in Chapter 5. A model was developed to describe the Sergeant-and-Soldiers and Majority-Rules phenomena in terms of two energy penalties: the helix reversal penalty and the mismatch penalty. We observed that the temperature had a strong influence on the degree of amplification and that opposite effects for the two phenomena were present. This could be related to the temperature dependence of the mismatch penalty. The helix reversal penalty was related to the strong intermolecular hydrogen bonds and was constant over the investigated temperature range. As a result, it was possible to influence the degree of amplification by changing the temperature. In Chapter 6 the synthesis of asymmetrically substituted benzene-1,3,5-tricarboxamide derivatives was presented. These molecules were prepared in order to investigate the role of molecular structure on the degree of chiral amplification. It was observed that the mismatch energy penalty depends on the number of stereocenters in the molecule and thereby affects the degree of chiral amplification. By studying the temperature dependence of the asymmetrical derivatives, the limits of chiral amplification have been investigated, revealing an optimal mismatch penalty for a given helix reversal penalty. In the final Chapter, investigations of other supramolecular polymers were described. It was shown that for an unambiguous determination and characterization of the supramolecular polymerization mechanisms, temperature-dependent experiments are essential. Also, for a cooperative supramolecular polymer, based on a chiral oligo(p-phenylene vinylene) (OPV) derivative, the self-assembly kinetics were studied using a stopped-flow setup. A lag phase, indicative for a cooperative mechanism, was observed and an estimate of the nucleus size was made based on the kinetic data.