Supramolecular system are held together by weak non-covalent bonds. Depending on the solvent environment, different weak interactions account for efficient complex formation. For example, hydrogen bonds are a major design element for supramolecular systems in organic, non-competitive solvents, but are challenging to exploit in water.
In our line of research we are mainly interested in, which weak interactions contribute to efficient binding in water. For example, we have found that the extremely high binding constants of cucurbiturils, which even outcompete the well-known straptavidin-biotin interaction (Ka > 1015 M-1), can be traced back to high-energy water inside the cucurbituril cavity. The main driving force for host-guest binding of cucurbiturils is thus a non-classical hydrophobic effect, i.e. a favorable enthalpic, and an unfavorable entropic contribution to binding.
Another weak interaction, which leads to efficient complex formation in water, is halogen bonding. This interaction is of comparable strength as hydrogen bonding, but is much less attenuated in water, and is thus currently emerging as a fundamental design principle for supramolecular host-guest complex formation in water.
Key references: (a) Angew. Chem. Int. Ed. 2014, 53, 11158-11171; (b) J. Am. Chem. Soc. 2013, 135, 14879-14888; (c) J. Am. Chem. Soc. 2012, 134, 19935-19941; (d) J. Am. Chem. Soc. 2012, 134, 15318-15323.