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, fluorescencebased 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. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host−dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.

The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes1–4. To remedy this, charged amphiphilic molecules have been classically used as carriers3,5. However, such amphiphilic carriers may cause aggregation and non-specific membrane lysis6,7. Here we show that globular dodecaborate clusters, and prominently B12Br122−, can function as anionic inorganic membrane carriers for a broad range of hydrophilic cargo molecules (with molecular mass of 146–4,500 Da). We show that cationic and neutral peptides, amino acids, neurotransmitters, vitamins, antibiotics and drugs can be carried across liposomal membranes. Mechanistic transport studies reveal that the carrier activity is related to the superchaotropic nature of these cluster anions8–12. We demonstrate that B12Br122− affects cytosolic uptake of different small bioactive molecules, including the antineoplastic monomethyl auristatin F, the proteolysis targeting chimera dBET1 and the phalloidin toxin, which has been successfully delivered in living cells for cytoskeleton labelling. We anticipate the broad and distinct delivery spectrum of our superchaotropic carriers to be the starting point of conceptually distinct cell-biological, neurobiological, physiological and pharmaceutical studies.

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.

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. We have now found that they can even activate membrane transport of short peptide substrates for kinases involved in signal transduction, whereas the respective phosphorylated products are much less efficiently transported. This allows regulation of membrane transport activity by protein kinase A (PKA) and protein kinase C (PKC), as well as monitoring of their activity in a label-free kinase assay.

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. Two portable chemosensor kits have been developed and tested to demonstrate its practical application in real-time monitoring.

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.

In recent years environmental awareness has grown due to the social dissatisfaction with the state of the environment. 1 As a result, more restrictive environmental laws have been introduced. In this context, air pollution constitutes one of the major problems in urban areas being the main sources of pollutants the combustion processes of fossil fuels used in power plants, vehicles and other incineration processes. The main combustion-generated air contaminants are nitrogen oxides (NO x ) which are considered the primary pollutants of the atmosphere, since they are responsible for the photochemical smog, the acid rain and ozone layer depletion. 2 On the other hand, NO is a well-known bioactive molecule which participates in a large variety of bioregulatory and immune response processes. 3 For these reasons intensive experimental research is being carried out for NO monitorization and several analytical techniques such as electrophoresis, electron paramagnetic resonance (EPR) or GC-mass spectroscopies, chemiluminescence or electrochemical methods have been developed for the detection of this hazard. 4 Even though these methods have certain benefits they also show some limitations typical involving poor specificity and the use of expensive experimental apparatus which restrict their application in practice. Recently, the development of fluorogenic probes has gained increasing interest as an alternative to classical instrumental procedures. 5 In this context fluorogenic probes are especially appealing because they allow simple detection in situ or/and at site usually without any sample pre-treatment. Moreover changes in emission can be detected using simple equipment and it is a very sensitive detection technique. In addition changes in emission properties can be detected to the naked eye making this procedure highly attractive.Several probes for the fluorogenic detection of NO have been reported. For instance poorly fluorescent vicinal diamines can be transformed to triazoles by NO resulting in a strong increase of fluorescence. 6 This mechanism is the basis of most fluorogenic NO probes. Moreover some new sensing protocols based NO-induced ring closure, 7 de-amination reactions, 8 or NO-induced aromatization 9 have been recently studied. Besides metal-based probes that take advantage of the reactivity of NO at the metal site have also been reported, and for instance nitric oxide sensing has been accomplished using Co II However some of these probes display some drawbacks such as dependence on the pH or tendency of certain dyes to form aggregates. Moreover because of the significance of NO to human health and diseases most of the probes have been tested to monitor NO production in vivo, whereas very few studies have been devoted to nitric oxide detection in air. Please do not adjust margins Please do not adjust margins characteristics, such as absorption and fluorescence transitions in the visible spectral region with high molar absorption coefficients and fluorescence quantum yields, good stability and no dep...

Efficient neutralization of nerve‐agent simulants by 1,3‐diindolylureas in a neutral medium was investigated (see scheme; DCP=diethylchlorophosphate, DCNP=diethylcyanophosphonate). The rate of hydrolysis of the simulants was found to increase by as much as 45 % in the presence of these compounds. A mechanism based on the simulant complexation was established.