From Guest‐Induced Crystallization to Molecular Imprinting: Calculation‐Guided Discovery of Hydrogen‐Bonded Tetrazole Frameworks for p‐Xylene Separation

Exploring host‐guest interactions to regulate hydrogen‐bonding assembly offers a promising approach for developing advanced porous crystal materials (PCMs). However, screening compatible guests with appropriate geometries and host‐guest interactions that could inhibit the dense packing of building blocks remains a primary challenge. This study presents a novel guest‐induced crystallization (GIC) strategy, guided by thermodynamic calculations, to develop porous hydrogen‐bonded organic frameworks (HOFs) using structurally challenging tetrazole building units. Thermodynamic principles are established from the crystal structure data and the density functional theory calculation of the formation energy (ΔE). This provides criteria to identify available guests in GIC, enabling the successful discovery of a hidden HOF that is kinetically challenging to crystallize. Furthermore, the potential application for p‐xylene (PX) separation is predicted by analyzing the ΔE of guest‐induced HOFs. A high PX selectivity (PX/m‐xylene=6.1, PX/o‐xylene=7.2, and PX/ethylbenzene=4.1) is achieved through selective inclusion of PX from C8 aromatic isomers within the guest‐induced HOFs. Significantly, the guest‐free HOF (HOF‐PX‐a), bearing PX‐templated cavities derived from molecular imprinting, shows a record‐high PX/ethylbenzene selectivity (21.7) in liquid adsorption. This work elucidates the underpinning self‐assembly rules of GIC for HOF construction, providing exciting new opportunities for the predictable assembly of PCMs for molecular recognition and target‐specific separations.