Abstract
Boron clusters are applied in medicinal chemistry because of their high stability in biological environments and intrinsic ability to capture neutrons. However, their intermolecular interactions with lipid membranes, which are critical for their cellular delivery and biocompatibility, have not been comprehensively investigated. In this study, we combine different experimental methods – Langmuir monolayer isotherms at the air–water interface, calorimetry (DSC, ITC), and scattering techniques (DLS, SAXS) – with MD simulations to evaluate the impact of closo ‐dodecaborate clusters on model membranes of different lipid composition. The cluster anions interact strongly with zwitterionic membranes (POPC and DPPC) via the chaotropic effect and cause pronounced expansions of lipid monolayers. The resulting lipid membranes contain up to 33 mol % and up to 52 weight % of boron cluster anions even at low aqueous cluster concentrations (1 mM). They show high (μM) affinity to the hydrophilic‐hydrophobic interface, affecting the structuring of the lipid chains, and therefore triggering a sequence of characteristic effects: ( i ) an expansion of the surface area per lipid, ( ii ) an increase in membrane fluidity, and ( iii ) a reduction of bilayer thickness. These results aid the design of boron cluster derivatives as auxiliaries in drug design as well as transmembrane carriers and help rationalize potential toxicity effects.