Halogen bonding is an electron density donation-based weak interaction that has so far almost exclusively been investigated in computational and crystallographic studies. It shows high similarities to hydrogen bonding; however, its applicability for molecular recognition processes long remained unappreciated and has not been thoroughly explored.The main goals of this project are (1) to take the major leap from solid state/computational to /solution/ investigations of halogen bonding by developing novel NMR methods, using these (2) perform the first ever systematic physicochemical study of halogen bonding in solutions, and (3) to apply the gained knowledge in structural biology through elucidation of the anaesthetic binding site of native proteins. This in turn is of direct clinical relevance by providing a long-sought understanding of the disease malignant hyperthermia.Model compounds will be prepared using solution-phase and solid-supported organic synthesis; NMR methods will be developed for physicochemical studies of molecular recognition processes and applied in structural biology through the study of the interaction of anaesthetics with proteins involved in cellular calcium regulation.Using a peptidomimetic model system and an outstandingly sensitive NMR technique I will systematically study the impact of halogen bond donor and acceptor sites, and of electronic and solvent effects on the strength of the interaction. The proposed method will quantify relative stability of a strategically-designed, cooperatively folding model system.A second NMR technique will utilize paramagnetic effects and permit simultaneous characterization of bond strength and geometry of weak intermolecular complexes in solution. The technique will first be validated on small, organic model compounds and subsequently be transferred to weak, protein-ligand interactions. It will be exploited to gain an atomic level understanding of anaesthesia.