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

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.