Solid-State Synthesis, X-ray Structure, and Guest Inclusion in Octahedral <b> M ₆ L ₄ </b> Cages Self-Assembled by Tris-pyridyl-benzene ( <b>TPB</b> )

The challenges found to self-assemble crystalline octahedral <b>M</b>_<b>6</b><b>L</b>_<b>4</b> metal-organic cages (<b>MOCs</b>) with the tridentate 2,4,6-tris(4-pyridyl)benzene (<b>TPB</b>) ligand and Pd²⁺ are due to the dihedral angle θ ∼ 36° between the pyridines and the central benzene ring (H_pyridine···H_benzene repulsion), the end-capping group, and the presence of suitable templating guests. Although it has recently been reported that the <b>TPB M₆L₄</b> cage (<b>Pd₆(TPB)₄</b>) can be formed in the solution state by only using the ethylenediamine (en) <i>cis</i> protecting group and Pd²⁺, its solid-state synthesis, 3D X-ray structure, and host-guest chemistry have not been reported. Here, using mechanochemistry by neat grinding (NG) <b>TPB</b> and (en)-Pd(NO₃)₂, we report the solid-state synthesis of <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b>, its solid-state structure, and its ability to include aromatic guests in aqueous media. In solution, the self-assembly of <b>TPB</b> and Pd²⁺ with a templating guest (i.e., 3-phenylpropanoic acid) (<b>G</b>_<b>1</b>) formed crystals of <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b>, suitable for single-crystal X-ray diffraction (SC-XRD). Density functional theory (DFT) calculations specific to the solid state showed different high <i>binding energy</i> (<i>E</i>_b) values for <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b> and the isostructural tris-pyridyl triazine (<b>TPT</b>)-based <b>MOC (Pd</b>_<b>6</b><b>(TPT)</b>_<b>4</b><b>)</b>. The higher stability of the <b>Pd</b>_<b>6</b><b>(TPT)</b>_<b>4</b> structure with respect to <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b> may be related to its higher <i>E</i>_b and density, a direct consequence of the higher degree of planarity of <b>TPT</b>, suggesting the importance of enthalpic/entropic contributions for the stability of these <b>M</b>_<b>6</b><b>L</b>_<b>4</b> structures in the solid state. The <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b> cage has an electron-rich hydrophobic cavity (∼450 ų) that is stable in water and in acidic conditions and can include four <b>G</b>_<b>1</b> in one <b>M</b>_<b>6</b><b>L</b>_<b>4</b>, as shown by titration experiments and using a guest model X-ray structure. In the solution state, ¹H NMR data show that <b>G</b>_<b>1</b> guest exchange/inclusion in <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b> occurs in the fast exchange regime. Hollow <b>Pd</b>_<b>6</b><b>(TPB)</b>_<b>4</b> is a strong candidate to be used in functional applications such as molecular recognition, guest stabilization, or unusual reactivity.