Steric Effects on the Chelation of Mn²⁺and Zn²⁺by Hexadentate Polyimidazole Ligands: Modeling Metal Binding by Calprotectin Site 2

Abstract

Recently, there has been increasing interest in the design of ligands that bind Mn 2 + with high affinity and selectivity, but this remains a difficult challenge. It has been proposed that the cavity size of the binding pocket is a critical factor in most synthetic and biological examples of selective Mn 2 + binding. Here, we use a bioinspired approach adapted from the hexahistidine binding site of the manganese-sequestering protein calprotectin to systematically study the effect of cavity size on Mn 2 + and Zn 2 + binding. We have designed a hexadentate, trisimidazole ligand whose cavity size can be tuned through peripheral modification of the steric bulk of the imidazole substituents. Conformational dynamics and redox potentials of the complexes are dependent on ligand steric bulk. Stability constants are consistent with the hypothesis that larger ligand cavities are relatively favorable for Mn 2 + over Zn 2 + , but this effect alone may not be sufficient to achieve Mn 2 + selectivity.

Synthesis and Characterization of Bipyridyl-(Imidazole)n Mn(II) Compounds and Their Evaluation as Potential Precatalysts for Water Oxidation

“…Although we have not yet attempted to study in detail the speciation and decomposition of the complexes under catalytic conditions at various pHs, we can hypothesize some reasons for their apparently low stability. It is well known that the binding affinity of chelating ligands to manganese(II) in aqueous solution tends to be relatively low (compared with other divalent first-row transition metals) [50,57]. The stability of this type of compound tends to be particularly low at non-neutral pH; under acidic conditions, it is possible that competitive protonation of the accessible basic sites on the ligand) results in the dechelation of the ligand.…”