Time-resolved monitoring of the permeability of analytes is of utmost importance in membrane research. Existing methods are restricted to single-point determinations or flat synthetic membranes, limiting access to biologically relevant kinetic parameters (permeation rate constant, permeation coefficients). We now use the recently introduced fluorescent artificial receptor membrane assay (FARMA) as a method to monitor, in real time, the permeation of indole derivatives through liposomal membranes of different lipid compositions. This method is based on the liposomal encapsulation of a chemosensing ensemble or “fluorescent artificial receptor”, consisting of 2,7-dimethyldiazapyrenium as a fluorescent dye and cucurbit[8]­uril as the macrocyclic receptor, that responds to the complexation of a permeating aromatic analyte by fluorescence quenching. FARMA does not require a fluorescent labeling of the analytes and allows access to permeability coefficients in the range from 10–8 to 10–4 cm s–1. The effect of temperature on the permeation rate of a series of indole derivatives across the phospholipid membranes was studied. The activation energies for permeation through POPC/POPS phospholipid membranes were in the range of 28–96 kJ mol–1. To study the effect of different lipid phases on the membrane permeability, we performed experiments with DPPC/DOPS vesicles, which showed a phase transition from a gel phase to a liquid-crystalline phase, where the activation energies for the permeation process were expected to show a dramatic change. Accordingly, for the permeation of the indole derivatives into the DPPC/DOPS liposomes, discontinuities were observed in the Arrhenius plots, from which the permeation activation energies for the distinct phases could be determined, for example, for tryptamine 245 kJ mol–1 in the gel phase and 47 kJ mol–1 in the liquid-crystalline phase.

An overarching challenge in the development of supramolecular sensor systems is to enhance their sensitivity, which commonly involves the synthesis of refined receptors with increased affinity to the analyte. We show that a dramatic sensitivity increase by 1-2 orders of magnitude can be achieved by encapsulating supramolecular chemosensors inside liposomes and exposing them to a pH gradient across the lipid bilayer membrane. This causes an imbalance of the influx and efflux rates of basic and acidic analytes leading to a significantly increased concentration of the analyte in the liposome interior. The utility of our liposomeenhanced sensors was demonstrated with various hostdye reporter pairs and sensing mechanisms, and we could easily increase the sensitivity towards multiple biologically relevant analytes, including the neurotransmitters serotonin and tryptamine.

A fluorescent perylene-based dye (PDI) was designed with two aromatic moieties at the imide position of the perylene core. The dye displayed contrasting behavior with water-soluble macrocycles. Cucurbit[n]urils (CB7 and CB8) reduced the selfaggregation of the dye molecules, while sulfonatocalixarenes (SCX4 and SCX5) and sulfonato-β-cyclodextrin (S-β-CD) resulted in a complexation-enhanced aggregation. In regard to potential applications, the CB8 * PDI complex served as an excellent reporter pair inside cells to detect the uptake of neurotransmitters by fluorescence.

Wirt‐Gast‐Komplexe. Werner M. Nau, Andreas Hennig et al. berichten in ihrer Zuschrift (e202207950) über die protonengradientengetriebene Sensitivitätssteigerung von supramolekularen Chemosensoren verkapselt in Liposomen. Der Ansatz wurde anhand verschiedener Wirt‐Farbstoff‐Reporterpaare und Sensormethoden demonstriert.

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