Self-Sorting Assembly of Molecular Trefoil Knots of Single Handedness

We report on the stereoselective synthesis of trefoil knots of single topological handedness in up to 90% yield (over two steps) through the formation of trimeric circular helicates from ligand strands containing either imine or, unexpectedly, amide chelating units and metal ion templates of the appropriate coordination character (zinc(II) for imines; cobalt(III) for amides). The coordination stereo chemistry of the octahedral metal complexes is determined by asymmetric carbon centers in the strands, ultimately translating into trefoil knots that are a single enantiomer, both physically and in terms of their fundamental topology. Both the imine-zinc and amide-cobalt systems display self-sorting behavior, with racemic ligands forming knots that individually contain only building blocks of the same chirality. The knots and the corresponding trimeric circular helicate intermediates (Zn(II)(3) complex for the imine ligands; Co(III)(3) complex for the amide ligands) were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and X-ray crystallography. The latter confirms the trefoil knots as 84-membered macrocycles, with each of the metal ions sited at a crossing point for three regions of the strand. The stereochemistry of the octahedral coordination centers imparts alternating crossings of the same handedness within each circular helicate. The expression of chirality of the knotted molecules was probed by circular dichroism: The topological handedness of the demetalated knots was found to have a greater effect on the CD response than the Euclidean chirality of an individual chiral center.