Topological prediction of palladium coordination cages

The preparation of functionalized, heteroleptic Pd_xL2_x coordination cages is desirable for catalytic and optoelectronic applications. Current rational design of these cages uses the angle between metal-binding (∠B) sites of the di(pyridyl)arene linker to predict the topology of homoleptic cages obtained via non-covalent chemistry. However, this model neglects the contributions of steric bulk between the pyridyl residues—a prerequisite for endohedrally functionalized cages, and fails to rationalize heteroleptic cages. We describe a classical mechanics (CM) approach to predict the topological outcomes of Pd_xL_2x coordination cage formation with arbitrary linker combinations, accounting for the electronic effects of coordination and steric effects of linker structure. Initial validation of our CM method with reported homoleptic Pd₁₂^LFu₂₄ (^LFu = 2,5-bis(pyridyl)furan) assembly suggested the formation of a minor topology Pd₁₅^LFu₃₀, identified experimentally by mass spectrometry. Application to heteroleptic cage systems employing mixtures of ^LFu (∠B = 127°) and its thiophene congener ^LTh (∠B = 149° ∠B_exp = 152.4°) enabled prediction of Pd₁₂L₂₄ and Pd₂₄L₄₈ coordination cages formation, reliably emulating experimental data. Finally, the topological outcome for exohedrally (^LEx) and endohedrally (^LEn) functionalized heteroleptic Pd_xL_2x coordination cages were predicted to assess the effect of steric bulk on both topological outcomes and coordination cage yields, with comparisons drawn to experimental data.