Grid‐Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions
Florian Nachon, Xavier Brazzolotto, José Dias, Charlotte Courageux, Wojciech Drożdż, Xiaoyu Cao, Artur R. Stefankiewicz, Jean‐Maríe Lehn
Abstract
We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.