Pore Engineering with Benzoate Derivatives in Supramolecular Copper-Adenine Systems for Water and Drug Sorption.

Porous supramolecular metal-organic frameworks (SMOFs) are versatile functional materials for controlled drug delivery and tailored water vapor sorption whose properties are deeply dependent on their specific internal microenvironment. Precisely tuning the internal pore environment of a coordination framework without perturbing its underlying topology remains a fundamental challenge in crystal engineering. Herein, we address this challenge in a family of water-stable copper-adenine supramolecular metal-organic frameworks (SMOFs). By systematically varying the monocarboxylate counterion, fine control over the accessible void space (ranging from 12 to 29%) was achieved, which dictates their water vapor sorption behavior through the simultaneous modification of steric hindrance and hydrophobicity. Furthermore, this work introduces a nondestructive magnetic sustentation technique that leverages the room-temperature paramagnetic nature of these frameworks to quantify the loading of highly insoluble drugs (5-fluorouracil, cycloserine, and gabapentin). In this context, drug uptake and release act as complementary experimental probes to validate our structural design. The structurally optimized Cu7Bz material achieved a notable 31.4% loading of 5-fluorouracil. Finally, in vitro assays on HCT116 colorectal cancer cells reveal that the compact pore architecture of 5-FU@Cu7Bz effectively mitigates the toxic "burst-release" effect, providing a sustained and potent antiproliferative response. These results establish counterion-directed pore engineering as a practical strategy for the design of advanced solid-state materials and introduce magnetic sustentation as a robust tool for evaluating complex host-guest systems.