Supramolecular Anchoring of NCN-Pincer Palladium Complexes into a β-Barrel Protein Host: Molecular-Docking and Reactivity Insights

Several prochiral NCN-pincer complexes of palladium(II), with hemilabile ligands and a long aliphatic chain, were synthesized and characterized spectroscopically. In some of the complexes, the presence of two different substituents on the N donor atoms made them stereogenic, so that they were isolated as a mixture of diastereoisomers, which could be differentiated by 1H NMR spectroscopy. Binding of some of these complexes to bovine β-lactoglobin by insertion within its inner cavity was theoretically investigated by molecular-docking simulations and was experimentally confirmed by CD spectroscopy. Adjunction of H-bond donor substituents on the ligand framework gave more-stable supramolecular protein–complex assemblies. These constructs were shown to catalyze aldol condensation reactions in aqueous media, affording, in some cases, the less-favorable cis product. Since the corresponding complexes exclusively gave the trans product in the absence of β-lactoglobulin, this unusual diastereoselectivity was ensued by the second sphere of coordination brought by the protein host.