Boron Cluster Anions Dissolve En Masse in Lipids Causing Membrane Expansion and Thinning.

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.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport.

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.

All-Inorganic Polyoxometalates Act as Superchaotropic Membrane Carriers.

Polyoxometalates (POMs) are known antitumoral, antibacterial, antiviral, and anticancer agents and considered as next-generation metallodrugs. Herein, a new biological functionality in neutral physiological media, where selected mixed-metal POMs are sufficiently stable and able to affect membrane transport of impermeable, hydrophilic, and cationic peptides (heptaarginine, heptalysine, protamine, and polyarginine) is reported. The uptake is observed in both, model membranes as well as cells, and attributed to the superchaotropic properties of the polyoxoanions.

Metallacarborane Cluster Anions of the Cobalt Bisdicarbollide-Type as Chaotropic Carriers for Transmembrane and Intracellular Delivery of Cationic Peptides.

Cobalt bisdicarbollides (COSANs) are inorganic boron-based anions that have been previously reported to permeate by themselves through lipid bilayer membranes, a propensity that is related to their superchaotropic character. We now introduce their use as selective and efficient molecular carriers of otherwise impermeable hydrophilic oligopeptides through both artificial and cellular membranes, without causing membrane lysis or poration at low micromolar carrier concentrations. COSANs transport not only arginine-rich but also lysine-rich peptides, whereas low-molecular-weight analytes such as amino acids as well as neutral and anionic cargos (phalloidin and BSA) are not transported.

Stability and p Modulation of Aminophenoxazinones and Their Disulfide Mimics by Host-Guest Interaction with Cucurbit[7]uril. Direct Applications in Agrochemical Wheat Models.

Aqueous solubility and stability often limit the application of aminophenoxazinones and their sulfur mimics as promising agrochemicals in a sustainable agriculture inspired by allelopathy. This paper presents a solution to the problem using host-guest complexation with cucurbiturils (). Computational studies show that is the most suitably sized homologue due to its strong affinity for guest molecules and its high water solubility.

Cephalosporin translocation across enterobacterial OmpF and OmpC channels, a filter across the outer membrane.

Gram-negative porins are the main entry for small hydrophilic molecules. We studied translocation of structurally related cephalosporins, ceftazidime (CAZ), cefotaxime (CTX) and cefepime (FEP). CAZ is highly active on E.

Discrete, Cationic Palladium(II)-Oxo Clusters via f-Metal Ion Incorporation and their Macrocyclic Host-Guest Interactions with Sulfonatocalixarenes.

We report on the discovery of the first two examples of cationic palladium(II)-oxo clusters (POCs) containing f-metal ions, [Pd O M {(CH ) AsO } (H O) ] (M=Ce , Th ), and their physicochemical characterization in the solid state, in solution and in the gas phase. The molecular structure of the two novel POCs comprises an octahedral {Pd O } core that is capped by eight M ions, resulting in a cationic, cubic assembly {Pd O M } , which is coordinated by a total of 16 terminal dimethylarsinate and eight water ligands, resulting in the mixed Pd -Ce /Th oxo-clusters [Pd O M {(CH ) AsO } (H O) ] (M=Ce, Pd Ce ; Th, Pd Th ). We have also studied the formation of host-guest inclusion complexes of Pd Ce and Pd Th with anionic 4-sulfocalix[n]arenes (n=4, 6, 8), resulting in the first examples of discrete, enthalpically-driven supramolecular assemblies between large metal-oxo clusters and calixarene-based macrocycles.

Boron clusters as broadband membrane carriers.

The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes. To remedy this, charged amphiphilic molecules have been classically used as carriers. However, such amphiphilic carriers may cause aggregation and non-specific membrane lysis.

Real-Time Parallel Artificial Membrane Permeability Assay Based on Supramolecular Fluorescent Artificial Receptors.

Parallel artificial membrane permeability assay (PAMPA) is a screening tool for the evaluation of drug permeability across various biological membrane systems in a microplate format. In PAMPA, a drug candidate is allowed to pass through the lipid layer of a particular well during an incubation period of, typically, 10-16 h. In a second step, the samples of each well are transferred to a UV-Vis-compatible microplate and optically measured (applicable only to analytes with sufficient absorbance) or sampled by mass-spectrometric analysis.

Supramolecular Chemistry in the Biomembrane.

The combination of supramolecular functional systems with biomolecular chemistry has been a fruitful exercise for decades, leading to a greater understanding of biomolecules and to a great variety of applications, for example, in drug delivery and sensing. Within these developments, the phospholipid bilayer membrane, surrounding live cells, with all its functions has also intrigued supramolecular chemists. Herein, recent efforts from the supramolecular chemistry community to mimic natural functions of lipid membranes, such as sensing, molecular recognition, membrane fusion, signal transduction, and gated transport, are reviewed.

Fluorescence Monitoring of Peptide Transport Pathways into Large and Giant Vesicles by Supramolecular Host-Dye Reporter Pairs.

The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescence-based method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host-dye reporter pair are encapsulated inside phospholipid vesicles.

Phosphorylation-Responsive Membrane Transport of Peptides.

Phosphorylation and dephosphorylation of peptides by kinases and phosphatases is essential for signal transduction in biological systems, and many diseases involve abnormal activities of these enzymes. Herein, we introduce amphiphilic calixarenes as key components for supramolecular, phosphorylation-responsive membrane transport systems. Dye-efflux experiments with liposomes demonstrated that calixarenes are highly active counterion activators for established cell-penetrating peptides, with EC values in the low nanomolar range.

A Boron Dipyrromethene (BODIPY)-Based Cu(II) -Bipyridine Complex for Highly Selective NO Detection.

A BODIPY-containing Cu(II) -bipyridine complex for the simple selective fluorogenic detection of NO in air and in live cells is reported. The detection mechanism is based on NO-promoted Cu(II) to Cu(I) reduction, followed by demetallation of the complex, which results in the clearly enhanced emission of the boron dipyrromethene (BODIPY) unit.

Synthesis and In Vitro Evaluation of a Photosensitizer-BODIPY Derivative for Potential Photodynamic Therapy Applications.

A new photosensitizer (1) based on the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold has been synthesized. 1 is water soluble and showed an intense absorption band at 490 nm (ɛ=77,600 cm(-1)  m(-1)) and an emission at 514 nm. In vitro toxicity of 1 in the presence of light and in darkness has been studied with HeLa, HaCaT, MCF-7, and SCC-13 cell lines.

Towards the design of organocatalysts for nerve agents remediation: The case of the active hydrolysis of DCNP (a Tabun mimic) catalyzed by simple amine-containing derivatives.

We report herein a study of the hydrolysis of Tabun mimic DCNP in the presence of different amines, aminoalcohols and glycols as potential suitable organocatalysts for DCNP degradation. Experiments were performed in CD3CN in the presence of 5% D2O, which is a suitable solvent mixture to follow the DCNP hydrolysis. These studies allowed the definition of different DCNP depletion paths, resulting in the formation of diethylphosphoric acid, tetraethylpyrophosphate and phosphoramide species as final products.

Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e.

Chromo-fluorogenic BODIPY-complexes for selective detection of V-type nerve agent surrogates.

Two new Eu(3+) and Au(3+) BODIPY-complexes capable of chromo-fluorogenically detecting micromolar concentrations of V-type nerve agent surrogates by a simple displacement assay are described.

Highly selective detection of nerve-agent simulants with BODIPY dyes.

Two chromo-fluorogenic probes, each based on the boron dipyrromethene core, have been developed for the detection of nerve-agent mimics. These chemosensors display both a color change and a significant enhancement of fluorescence in the presence of diethylcyanophosphonate (DCNP) and diisopropylfluorophosphate (DFP). No interference from other organophosphorus compounds or acids has been observed.

A new selective fluorogenic probe for trivalent cations.

A new selective chromo-fluorogenic probe for Fe(3+), Cr(3+) and Al(3+) is reported. Detection limits are in the μM range and the fluorogenic sensing ability could be observed by the naked eye when illuminated with UV-light. No response is observed with divalent cations.