Abstract
<jats:p>The spatial organization of guest molecules within metal-organic frameworks strongly influence adsorption, transport, separation, and reactivity, yet controlling guest location across chemically and structurally distinct pore environments remains challenging. Here, we demonstrate that local pore polarity directs vapor-phase guest positioning within the interconnected hydrophilic and hydrophobic pores of NU-1000. Water and heptane were selected as representative polar and nonpolar guests, respectively. Water preferentially occupies hydrogen-bonding-rich pore environments before populating the hydrocarbon-rich pores, whereas heptane exhibits the opposite filling sequence. Vapor-phase adsorption isotherms, combined with powder X-ray diffraction-derived differential electron density analysis, reveal these polarity-dependent guest distributions and filling pathways. These findings establish pore polarity as a key design parameter for programming guest organization in hierarchical MOFs and provide a foundation for creating confined environments that enable phase separation, interfacial reactions, and other spatially controlled chemical functions.</jats:p>