Entropy directs the self-assembly of supramolecular palladium coordination macrocycles and cages.

The self-assembly of palladium-based cages is frequently rationalized via the cumulative enthalpy (Δ H ) of bonds between coordination nodes (M, i.e. , Pd) and ligand (L) components. This focus on enthalpic rationale limits the complete understanding of the Gibbs free energy (Δ G ) for self-assembly, as entropic (Δ S ) contributions are overlooked. Here, we present a study of the M 2 lin L 3 intermediate species (M = dinitrato( N , N , N ', N '-tetramethylethylenediamine)palladium(ii), lin L = 4,4'-bipyridine), formed during the synthesis of triangle-shaped (M 3 lin L 3 ) and square-shaped (M 4 lin L 4 ) coordination macrocycles. Thermochemical analyses by variable temperature (VT) 1 H-NMR revealed that the M 2 lin L 3 intermediate exhibited an unfavorable (relative) Δ S compared to M 3 lin L 3 (triangle, Δ T Δ S = +5.22 kcal mol -1 ) or M 4 lin L 4 (square, Δ T Δ S = +2.37 kcal mol -1 ) macrocycles. Further analysis of these constructs with molecular dynamics (MD) identified that the self-assembly process is driven by Δ G losses facilitated by increases in solvation entropy (Δ S solv , i.e. , depletion of solvent accessible surface area) that drives the self-assembly from "open" intermediates toward "closed" macrocyclic products. Expansion of our computational approach to the analysis of self-assembly in Pd n ben L 2 n cages ( ben L = 4,4'-(5-ethoxy-1,3-phenylene)dipyridine), demonstrated that Δ S solv contributions drive the self-assembly of both thermodynamic cage products ( i.e. , Pd 12 ben L 24 ) and kinetically-trapped intermediates ( i.e. , Pd 8 c L 16 ).