kcal/mol more energy on average to bind to K + than Na + . Furthermore, for the set of complexes that natively bind K + , there is a strong positive correlation between the differential binding energies of K + vs Na + with those of K + vs Li + (Pearson's r = 0.887), as both involve an exchange of a larger ion to a smaller ion. The same trend occurs for complexes which natively coordinate Li + when exchanging to larger ions Na + and K + (r = 0.893). For complexes which natively bind the mediumsized Na + ion, the differential binding energy of Na + vs K + has a negative correlation to the differential binding energy of Na + vs Li + (r = -0.430). That is, those complexes that are most While the energetic trends with ion size follow chemical intuition, we find exceptions that represent promising avenues for tuning selectivity. We observe in the complex FOVVUJ that its planar geometry of 4 coordinating N atoms favors the largest ion K + and the smallest ion Li + over the medium-sized Na + (Figure ). One possible explanation for this unexpected Li + > K + > Na + preference that runs counter to intuition from ion size is the existence of multiple stable coordination numbers for different ion species when solvated in water , which translates to ligand binding preferences. A planar arrangement of four coordinating atoms may exhibit a preference for Li + and K + , which both have stable water coordination numbers of four and six, where for a coordination number of six the octahedral coordination corresponds to four equatorial (similar to the four-coordinated planar geometry of FOVVUJ) and two axial waters. Na + on the other hand is only found with stable water coordination numbers of five and six, and hence may be destabilized when coordinated by four planar N atoms. These findings suggest that utilizing planar coordination frameworks such as functionalized 2D graphene or graphene oxides may be viable strategies for selective binding of K + and Li + in membrane design.