Revisiting closo -Dodecaborate Anions as Superchaotropic Carriers through a Microsolvation View

Abstract Dodecaborate clusters have emerged as unique inorganic membrane carriers for bioactive cargo molecules because of their superchaotropic nature, yet the transport mechanism remains elusive. Herein, we combine gas-phase negative-ion photoelectron spectroscopy (NIPES) and multiscale simulations on microhydrated B12X122–·nH2O (X = H, Br; n = 0–20) to investigate electronic structures and microsolvation dynamics. Our results show that water molecules in the first solvation shell of these superchaotropic borane anions tend to self-aggregate rather than encapsulate the boron core, driven by stronger water–water interactions relative to water–ion interactions. Compared with B12H122–, B12Br122– exhibits a lower hydration wrap degree and larger van der Waals contact surface with drug molecules, and its higher B–Br bond polarizability enables stronger electrostatic and orbital interactions for direct binding. This work establishes a direct link between microsolvation configuration and carrier activity, offering an atomistic perspective for the rational design of borane-based delivery systems beyond the classical Hofmeister limit.