Selective recognition of bis-imidazoles by complementary bis-metal ion complexes

Metal ion complexes that bind protein surfaces at exposed coordinating ligands can be exploited in selective protein recognition. For example, immobilized metal-affinity chromatography (IMAC), a technique used extensively for protein purification, discriminates proteins based on the nature and multiplicity of surface-exposed ligands, usually the imidazole moiety of histidine. To design complexes capable of selectively recognizing an individual protein or other target molecule, the spatial distribution of metal ions can be matched to the distribution of coordinating ligands on the target molecule. A similar proposal, when used as the basis for template polymerization in the presence of the target molecule, yielded solid, Cu^(2+) -containing polymers that could discriminate bis-imidazole "protein analogs" so similar that they could not be separated by reverse-phase HPLC. The "rationally designed" model system reported here demonstrates that receptor complexes containing as few as two properly-positioned metal ions can selectively recognize target molecules with a complementary spatial distribution of metal-coordinating ligands. Complexes such as these may have applications as receptors for biological molecules that are characterized by unique patterns of surface coordinating ligands.