The interaction of small molecules with phospholipid membranes studied by ¹H NOESY NMR under magic-angle spinning

The interaction of small molecules with lipid membranes and the exact knowledge of their binding site and bilayer distribution is of great pharmacological importance and represents an active field of current biophysical research. Over the last decade, a highly resolved ¹H solid-state NMR method has been developed that allows measuring localization and distribution of small molecules in membranes. The classical solution ¹H NMR NOESY technique is applied to lipid membrane samples under magic-angle spinning (MAS) and NOESY cross-relaxation rates are determined quantitatively. These rates are proportional to the contact probability between molecular segments and therefore an ideal tool to study intermolecular interactions in membranes. Here, we review recent ¹H MAS NOESY applications that were carried out to study lateral lipid organization in mixed membranes and the interaction of membranes with water, ethanol, small aromatic compounds, peptides, fluorescence labels, and lipophilic nucleosides.