Systematic Synthesis of Large Porous Organic Cages Driven by Steric Hindrance

Large organic cages (>3 nm) hold great promise for enhancing gas adsorption capacity and encapsulating bulky guests, such as nanoparticles and biomolecules. However, their synthesis remains challenging due to entropic penalties favoring smaller cages and interlocked byproducts during self-assembly. Here, we present a steric hindrance-driven strategy to systematically construct a series of stable [6 + 12] cages via imine condensation between tetratopic and ditopic synthons. Introducing bulky substituents to the tetratopic building blocks effectively suppressed entropic competition, directing assembly exclusively toward <b>Tet</b>^<b>6</b><b>Di</b>^<b>12</b> topologies. Notably, enhanced steric crowding induced an unprecedented triangular orthobicupola (Johnson solid <b><i>J</i>₂₇</b>) geometry─the first report of this topology in organic cages. Molecular dynamics and density functional theory calculations confirmed that the increased steric bulk thermodynamically favors <b>Tet</b>^<b>6</b><b>Di</b>^<b>12</b> over smaller analogs (<b>Tet</b>^<b>3</b><b>Di</b>^<b>6</b> and <b>Tet</b>^<b>4</b><b>Di</b>^<b>8</b>). Single-crystal structures revealed that the large-sized cages self-assemble into unique spatial arrangements of alternating ultramicro-mesoporous three-dimensional pore networks, with intrinsic frustration in close packing conferring permanent porosity.