Force Spectroscopy of Metal-Crown Ether Multivalency: Effect of Local Environments on Energy Landscape and Sensing Kinetics

Sandwich complexation involving alkali or alkaline‐earth metals, multivalency, and effects associated with local environments is widely encountered in biological and synthetic systems yet the mechanic properties remain unexplored. Herein, AFM (atomic force microscopy)‐based single‐molecule force spectroscopy is employed to investigate a classical model of Mn+[15C5]2, a metal cation hosted jointly by two 15‐crown‐5 moieties immobilized on both the substrate and the AFM tip. Factors reportedly promoting the recognition performance are examined. The rupture force required to break apart Mn+[15C5]2 is found to be in the order of tens of pico‐Newton, e.g., fβ=31 pN for K+[15C5]2. The presence of a second functional group, carboxylate, confers K+[15C5]2 with a longer lifetime (from 13 to 16 ms), faster association (from 0.4 to 1.3×106 M−1 s−1), and slower dissociation (from 77 to 62 s−1). The effect of local environments is significant on association yet less critical on dissociation pathways. Break it up! The mechanical strength of metal–crown ether multivalent interactions is unveiled quantitatively by single‐molecule force spectroscopy. The rupture force is on the order of tens of pico‐Newton. Dynamic force spectroscopy shows that the effect of local environments is distinct on affinity association yet relatively insignificant on the dissociation reaction.