Barba-Bon Andrea, El Haitami Alae, Pasquier Coralie, Nikšić-Franjić Ivana, Diat Olivier, Bauduin Pierre, Cantin Sophie, Nau Werner M
School of Science, Constructor University, Campus Ring 1, 28759, Bremen, Germany.
Laboratoire de Physicochimie des Polymères et des Interfaces (LPPI), Université de Cergy-Pontoise, 5 mail Gay, Lussac, F-95031, Cergy-Pontoise-Cedex, France.
Angew Chem Int Ed Engl. 2024 Dec 16;63(51):e202412834. doi: 10.1002/anie.202412834. Epub 2024 Oct 31.
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.
硼簇因其在生物环境中的高稳定性和捕获中子的内在能力而被应用于药物化学。然而，它们与脂质膜的分子间相互作用，这对其细胞递送和生物相容性至关重要，尚未得到全面研究。在本研究中，我们将不同的实验方法——空气-水界面的朗缪尔单分子层等温线、量热法（差示扫描量热法、等温滴定量热法）和散射技术（动态光散射、小角X射线散射）——与分子动力学模拟相结合，以评估闭式十二硼酸盐簇对不同脂质组成的模型膜的影响。簇阴离子通过离液效应与两性离子膜（1-棕榈酰-2-油酰基-sn-甘油-3-磷酸胆碱和二棕榈酰磷脂酰胆碱）强烈相互作用，并导致脂质单分子层明显扩张。即使在低水相簇浓度（1 mM）下，所得脂质膜中硼簇阴离子的含量也高达33 mol%和52重量%。它们对亲水-疏水界面表现出高（微摩尔）亲和力，影响脂质链的结构，从而引发一系列特征效应：（i）每个脂质的表面积增加，（ii）膜流动性增加，以及（iii）双层厚度减小。这些结果有助于设计硼簇衍生物作为药物设计中的辅助剂以及跨膜载体，并有助于阐明潜在的毒性效应。
