Voltammetric Characterization of Redox-Inactive Guest Binding to LnIII[15-Metallacrown-5] Hosts Based on Competition with a Redox Probe



A novel competitive binding assay was implemented to monitor the binding of a redox inactive substrate to a redox inactive metallacrown host based on its competition with ferrocene carboxylate (FcC) using cyclic voltammetry (CV). First, the binding of FcC to LnIII[15-MCmath image-5] (LnMC) hosts was characterized by cyclic voltammetry. It was shown that the voltammetric half wave potentials, E1/2, shifted to more positive potentials upon the addition of LnMC. The explicit dependence of E1/2 with the concentration of LnMC was used to determine the association constants for the complex. The FcC binding strength decreased with larger central lanthanide metals in the LnMC hosts, and substantially weaker binding was observed with LaIII. X-ray crystallography revealed that the hydrophobic host cavity incompletely encapsulated FcC when the guest was bound to the nine-coordinate LaIII, suggesting the LnMC’s ligand side chains play a substantial role in guest recognition. With knowledge of the MC-FcC solution thermodynamics, the binding affinity of a redox inactive guest was then assessed. Addition of sodium benzoate to a LnMC and FcC mixture resulted in E1/2 shifting back to the value observed for FcC in the absence of LnMC. The association constants between benzoate and LnMC’s were calculated via the competitive binding approach. Comparison with literature values suggests this novel assay is a viable method for determining association constants for host–guest systems that exhibit the proper electrochemical behavior. Notably, this CV competitive binding approach does not require the preparation of a modified electrode or a tethered guest, and thus can be generalized to a number of host–guest systems.