Analysis and Refinement of Host–Guest Interactions in Metal–Organic Frameworks

[Image: see text] Metal–organic frameworks (MOFs) are a class of hybrid porous materials characterized by their periodic assembly using metal ions and organic ligands through coordination bonds. Their high crystallinity, extensive surface area, and adjustable pore sizes make them promising candidates for a wide array of applications. These include gas adsorption and separation, substrate binding, and catalysis, of relevance to tackling pressing global issues such as climate change, energy challenges, and pollution. In comparison to traditional porous materials such as zeolites and activated carbons, the design flexibility of organic ligands in MOFs, coupled with their orderly arrangement with associated metal centers, allows for the precise engineering of uniform pore environments. This unique feature enables a rich variety of interactions between the MOF host and adsorbed gas molecules, which are fundamental to understanding the observed uptake capacity and selectivity for target gas molecules and thus the overall performance of the material. In this Account, a data set for three-dimensional MOFs has been constructed based upon the structural analysis of host–guest interactions using the largest experimental database, the Cambridge Structural Database (CSD). A full screening was performed on structures with guest molecules of H(2), C(2)H(2), CO(2), and SO(2), and the relationship between the primary binding site, the isosteric heats of adsorption (Q(st)), and the adsorption uptake was extracted and established. We review the methodologies to refine host–guest interactions based primarily on our studies on the host–guest chemistry of MOFs. The methods include ligand functionalization, variation of metal centers, formation of defects, addition of single atom sites, and control of pore size and structure. In situ structural and dynamic investigations using diffraction and spectroscopic techniques are powerful tools to visualize the details of host–guest interactions upon the above modifications, affording key insights into functional performance at a molecular level. Finally, we give an outlook of future research priorities in the study of host–guest chemistry in MOF materials. We hope this Account will encourage the rational development and improvement of future MOF-based sorbents for applications in challenging gas adsorption, separations, and catalysis.