Prof. Werner Nau
Jacobs University Bremen

Supramolecular chemists have explored and developed a large portfolio of noncovalent driving forces to understand and ultimately control assembly formation. The formation of discrete host-guest complexes in aqueous solution has proven particularly instructive in this respect, also due to its biological implications. Besides electrostatic interactions between host and guest, the driving force portfolio in water has been limited to two attractive interactions. These include the hydrophobic effect and dispersion interactions, which are additionally difficult to dissect. We present results which - conceptually - expand the portfolio of noncovalent driving forces in aqueous host-guest chemistry. First, besides the classical, entropically driven hydrophobic effect related to guest desolvation, a nonclassical, enthalpically driven counterpart related to the desolvation of intermediary sized host cavities needs to be considered, which can be traced back to the removal of high-energy cavity water as the driving force. Second, the hydrophobic effect can be further dissected into two separate components, one related to differential cavitation energies, the other one related to differential dispersion interactions. In supramolecular design, both need to be optimized separately, with the result that very small, non-solvated cavities contribute an extra driving force in the binding of very small guests such as gases; this can be exploited, for example, for gas-storage materials. Finally, through recent studies in the binding of large, so-called superchaotropic, anions to hydrophobic cavities, the chaotropic effect has emerged as a thermodynamically orthogonal driving force to the hydrophobic effect. The two effects derive from a different aqueous solvation pattern of hydrophobic and chaotropic guest molecules, which ultimately drives their desolvation and binding to hydrophobic cavities either entropically (hydrophobic) or enthalpically (chaotropic). Most recently, the first biological application of the chaotropic effect has been introduced, which related to the use of superchaotropic ions for transmembrane transport of amino acids, peptides, and drugs.

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