biostudies-literatureUnknown29(5)Aoun PIn the biomimetic context, many studies have evidenced the importance of the 1^st and 2^nd coordination sphere of a metal ion for controlling its properties. Here, we propose to evaluate a yet poorly explored aspect, which is the nature of the cavity that surrounds the metal labile site. Three calix[6]arene-based aza-ligands are compared, that differ only by the nature of cavity walls, anisole, phenol or quinone (L^OMe , L^OH and L^Q ). Monitoring ligand exchange of their Zn^II complexes evidenced important differences in the metal ion relative affinities for nitriles, halides or carboxylates. It also showed a possible sharp kinetic control on both, metal ion binding and ligand exchange. Hence, this study supports the observations reported on biological systems, highlighting that the substitution of an amino-acid residue of the enzyme active site, at remote distance of the metal ion, can have strong impacts on metal ion lability, substrate/product exchange or selectivity.Chemistry (Weinheim an der Bergstrasse, Germany)e202202934https://www.ebi.ac.uk/biostudies/studies/S-EPMC10107959biostudies-literatureSelective Metal-ion Complexation of a Biomimetic Calix[6]arene Funnel Cavity Functionalized with Phenol or Quinone.PMC10107959Jabin IZhurkin FColasson BReinaud OAoun PNyssen NRichard SfalseSelective Metal-ion Complexation of a Biomimetic Calix[6]arene Funnel Cavity Functionalized with Phenol or Quinone.In the biomimetic context, many studies have evidenced the importance of the 1^st and 2^nd coordination sphere of a metal ion for controlling its properties. Here, we propose to evaluate a yet poorly explored aspect, which is the nature of the cavity that surrounds the metal labile site. Three calix[6]arene-based aza-ligands are compared, that differ only by the nature of cavity walls, anisole, phenol or quinone (L^OMe , L^OH and L^Q ). Monitoring ligand exchange of their Zn^II complexes evidenced important differences in the metal ion relative affinities for nitriles, halides or carboxylates. It also showed a possible sharp kinetic control on both, metal ion binding and ligand exchange. Hence, this study supports the observations reported on biological systems, highlighting that the substitution of an amino-acid residue of the enzyme active site, at remote distance of the metal ion, can have strong impacts on metal ion lability, substrate/product exchange or selectivity.2023-01-01T00:00:00Z2023 Jan2025-04-27T02:36:29.932Z2025-04-06T18:37:59.088ZS-EPMC101079593632164010.1002/chem.202202934