Salluce, GiuliaFolgar Cameán, YerayBarba Bon, AndreaNikšić Franjić, IvanaEl Anwar, SuzanGrüner, BohumírLostalé Seijo, IreneNau, Werner M.Montenegro García, Javier2024-09-232024-09-232024-05-07Angew. Chem. Int. Ed. 2024, 63, e2024042861433-7851http://hdl.handle.net/10347/34843Perhalogenated closo-borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure–activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane-lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transportersengAtribución-NoComercial 4.0 Internacional© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposeshttp://creativecommons.org/licenses/by-nc/4.0/BoronCluster compoundsPeptide deliveryMembranesVesiclesjournal article10.1002/anie.2024042861521-3773open access