Bicyclo[3.3.1]nonanes as Scaffolds in Supramolecular Chemistry: From Host-Guest Systems to Hydrogen-Bonded Aggregates

This thesis describes the use of bicyclo[3.3.1]nonane and its heteroanalogue 1,5- diazabicyclo[3.3.1]nonane as scaffolds in different supramolecular systems. The thesis is divided into two parts, with the first part (chapter 2–4) focusing on the development and applications of a synthetic receptor based on a Tröger’s base motif fused with 18-crown-6 moieties. In chapter 3, NMR titration methodology was used to determine relative association constants and binding energies of the binding between the receptor and differently substituted bisammonium ligands. A small but evident discrimination based solely on the substituent was found, with phenyl- and methyl-substituted ligands forming stronger receptor-ligand complexes than ligands with no or larger substituents. By combining the estimated relative binding energies with results from conformational analyses of the receptor-ligand complexes, the free binding energies between a methyl or a phenyl group and an aromatic cavity were estimated to -0.40 and -0.80 kcal/mol, respectively, which is comparable to previously reported values for similar CH-π and π-π interactions.

In chapter 4, the consecutive binding of potassium ions to the same ditopic receptor in water is studied. ITC experiments revealed a counterintuitive result: that the binding of the second potassium ion is enthalpically favored compared to the binding of the first. A combination of experiments and simulations were employed to investigate how different factors influence the thermodynamics of the binding process, resulting in the finding that both the counterion and intrinsic favorable interactions between the two potassium-bound crown-ethers contribute to the observed thermodynamic trends. Although further investigations are needed to fully elucidate the different contributions, the herein presented study offers valuable insights into factors affecting receptor/ligand interactions in water.

The second part of the thesis (chapter 5–6) describes hydrogen-bonding monomers capable of self- assembling into cyclic and tubular aggregates. With the aim of developing amphiphilic monomers, polyethylene glycol (PEG) chains were introduced to the bicyclic backbone of the monomers. The synthesis and self-assembly of two new PEGylated monomers is described and compared to previously reported alkylated analogues. Both new monomers were capable of forming hydrogen-bonded cyclic aggregates. The effect of the PEG chains on the aggregate stability was found to depend on the hydrogen bond strength. One of the monomers exhibited the desired amphiphilicity and could be extracted from an aqueos solution into a chloroform solution, where self-assembly into cyclic tetramers occurred.