Exploiting Supramolecular Interactions to Control Isomer Distributions in Reduced-Symmetry [PdL] Cages.

High-symmetry metallosupramolecular architectures (MSAs) have been exploited for a range of applications including molecular recognition, catalysis, and drug delivery. Recently, there have been increasing efforts to enhance those applications by generating reduced-symmetry MSAs. Here we report our attempts to use supramolecular (dispersion and hydrogen-bonding) forces and solvophobic effects to generate isomerically pure [Pd(L)] cage architectures from a family of new reduced-symmetry ditopic tripyridyl ligands. The reduced-symmetry tripyridyl ligands featured either solvophilic polyether chains, solvophobic alkyl chains, or amino substituents. We show using NMR spectroscopy, high-performance liquid chromatography, X-ray diffraction data, and density functional theory calculations that the combination of dispersion forces and solvophobic effects does not provide any control of the [Pd(L)] isomer distribution with mixtures of all four cage isomers (HHHH, HHHT, -HHTT, or -HTHT, where H = head and T = tail) obtained in each case. More control was obtained by exploiting hydrogen-bonding interactions between amino units. While the cage assembly with a 3-amino-substituted tripyridyl ligand leads to a mixture of all four possible isomers, the related 2-amino-substituted tripyridyl ligand generated a -HHTT cage architecture. Formation of the -HHTT [Pd(L)] cage was confirmed using NMR studies and X-ray crystallography.