Monovalent cation binding to model systems and the macrocyclic depsipeptide, emodepside.

This study focuses on the systematic exploration of the emodepside conformations bound to monovalent K + ion using quantum mechanical density functional theory (DFT) calculations at the M06-2X/6-31+G(d,p) level of theory. Nine conformers of emodepside and their complexes with K + ion were characterized as stationary points on the potential energy surface. The conformational isomers were examined for their 3D structures, bonding, energetics, and interactions with the cation. A cavitand-like structure (CC) is identified to be the energetically most stable arrangement. To arrive at a better understanding of the K + ion binding, calculations were initially performed on complexes formed by the K + and Na + ions with model ligands (methyl ester and N,N-dimethyl acetamide). Both the natural bond orbital (NBO) method and the block-localized wavefunction (BLW) energy decomposition approach was employed to assess the bonding and energetic contributions stabilizing the ion-bound model complexes. Finally, the solvent effect was evaluated through complete geometry optimizations and energy minimizations for the model ion-ligand complexes and the emodepside-K + bound complexes using an implicit solvent model mimicking water and DMSO.