Ion-Exchange Selectivity in Alginate Egg-Box Models: Effect of the G-Rich and M-Rich Microenvironment on the Stabilization of Divalent Metal Cations

In this study, ion-exchange selectivity in alginate egg-box-type models containing guluronate-rich (PG) and mannuronate-rich (PM) microenvironments was investigated by density functional theory using a cluster–continuum approach in water. The objective was to determine how local sequence modulates the replacement of Ca2+ by Cu2+, Ni2+, Pb2+, and V2+ through combined structural, thermodynamic, and electronic analyses. All structures were optimized in aqueous medium and vibrationally validated, and selectivity was quantified through the free energy of exchange (ΔGexch) for a binuclear Ca2+ ↔ M2+ scheme. The results revealed a strong microenvironmental dependence. In PG, all exchanges were thermodynamically unfavorable, with positive ΔGexch values for Cu2+ (170.86 kcal mol−1), Ni2+ (114.55 kcal mol−1), Pb2+ (24.33 kcal mol−1), and V2+ (148.05 kcal mol−1). In contrast, in PM, Ni2+ and Pb2+ became favorable, with ΔGexch values of −60.93 and −113.00 kcal mol−1, respectively, whereas Cu2+ and V2+ remained unfavorable. Structurally, Ni2+ displayed the most compact and regular coordination, whereas Pb2+ was stabilized through broader and more anisotropic accommodation within the pocket. Overall, the results indicate that, within the present model, selectivity arises from the interplay among partial dehydration, metal–oxygen coordination, pocket preorganization, and noncovalent stabilization, rather than from any single descriptor taken in isolation.