The properties of molecules in solution are of great interest for the investigation of biological systems or the development of new therapeutics. Pharmacological properties such as aqueous solubility or passive membrane permeability are important for the latter , with guidelines such as Lipinski's rule of five (Ro5) or Veber's rule presenting recommendations for the rational design of orally available drugs. However, these rules can often not be fulfilled by larger compounds. While newer drugs increasingly exceed the Ro5 limits (especially in terms of molecular weight ), it is still challenging to obtain drug-like properties and especially oral bioavailability with larger compounds . It has been observed that macrocyclic compounds (i.e., compounds with a ring of 12 or more atoms) can exhibit a favorable combination of passive membrane permeability , binding affinity, and solubility compared to their acyclic counterparts of similar size and composition . This makes them promising candidates for the development of novel therapeutics. Although several de novo designed scaffolds have been reported , most macrocyclic drugs so far are derived from natural products , in part because of the difficulty of predicting the binding affinity and pharmacological properties of novel compounds .