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.

Perhalogenated 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 transporters.

We carried out an investigation of the performances of 18 density functionals (DFs) for modelling the mechanisms and kinetics of the aqueous phase reactions between the α-hydroxyisopropyl radical and 9 organic substrates. The primary goal was to evaluate the applicability of density functional theory specifically in conjunction with the polarizable continuum model (DFT/PCM) for a fully implicit description of the aqueous environment. Accordingly, the solute is augmented with the explicit molecule(s) of the water solvent only when it is confirmed that the water participates in the reaction mechanism directly and not just as a potential donor or acceptor of additional hydrogen bonds. The tested DFs are chosen by systematically ascending the Jacob's ladder of DFs with particular emphasis on the versatile Minnesota family. For most of the DFs we used the empirical corrections for the dispersion in accordance with Grimme's D3 or D3-BJ models. The optimum DFs are determined on the basis of the lowest mean absolute errors (MAEs) and the largest Pearson correlation coefficients (PCCs) with respect to the set of experimentally determined rate constants. The studied substrates are carbon tetrachloride (CCl₄), chloroform (CHCl₃), trichloroacetate (Cl₃Ac⁻), chloral hydrate (ClH), iodoacetate (IAc⁻), iodoacetamide (IAm), 5-bromouracil (BrU), 5-nitrouracil (NO₂U), and cysteamine (Cys⁺). The mechanisms that contribute dominantly to the observed rate constants are: chlorine abstractions for CCl₄, CHCl₃, Cl₃Ac⁻, and ClH; proton-coupled electron transfer (PCET) for IAc⁻; water-assisted PCET and iodine abstraction for IAm; ortho-addition for BrU and NO₂U; and hydrogen atom abstraction from the sulphur atom for Cys⁺. It is found that in the DFT/PCM setting climbing up the Jacob's ladder does not necessarily imply a systematically increasing accuracy. Thus, M06-D3 and PBE0-D3 exhibit the best performance according to the lowest MAEs (1.10 and 1.26 kcal mol⁻¹ MAEs in the Gibbs free energies of activation), and M06-D3, M06-2X-D3 and MN15 according to the largest PCCs (0.95, 0.94, and 0.94). In a surprising contrast, the three tested double-hybrid DFs, B2PLYP-D3, DSD-PBEP86, and PBEQIDH, all exhibit comparatively large MAEs and poor PCCs, and therefore do not appear well-suited for use in the DFT/PCM framework.

Cationic calix[6]arene and calix[4]arene derivatives non-covalently bind into a DNA minor groove or RNA major groove and form tweezer-like complexes with nucleotides.

Pyrene-armed calix[4]arene conjugates non-covalently bind to DNA/RNA, as well as to mononucleotides, with an amazing affinity.