ABSTRACT Precise modulation of ion permselectivity in synthetic membranes is crucial for advancing separation and energy conversion technologies. Here, we demonstrate that neutral substituents can reprogram the intrinsic ion selectivity of cationic covalent organic framework (COF) membranes by introducing secondary local interactions that compete with long‐range Coulombic forces. Using triaminoguanidinium‐based COFs as a model system, we systematically varied both the number and type of substituents on 1,3,5‐trialdehyde linkers. The introduced substituents generated secondary interactions that modulated the primary Coulombic interactions between guanidinium cations and Cl – counterions. When two or more hydroxyl groups were present on the aldehyde linkers, these interactions immobilized anions and inverted the effective surface potential from positive to negative, thereby switching the transport polarity from anion‐ to cation‐selective behavior. In contrast, methoxy substitution weakened Coulombic interactions, enhancing anion selectivity. This tunable control over the local chemical microenvironment enabled programmable and reversible ion permselectivity without altering the permanent framework charge. Leveraging this mechanism, we achieved record‐high ionic thermoelectric performance, 25.9 W m −2 for a single membrane and 39.1 W m − 2 for a stacked configuration under a 50 K temperature gradient. This work establishes substituent‐mediated secondary interactions as a general and powerful strategy for programming ion transport, bridging biological selectivity principles with the design of adaptive COF‐based membranes for energy harvesting and separation.
Yi et al. (Sun,) studied this question.