Structures and internal dynamics of diphenylether and its aggregates with water.

We report on a detailed multi-spectroscopic analysis of the structures and internal dynamics of diphenylether and its aggregates with up to three water molecules by employing molecular beam experiments. The application of stimulated Raman/UV and IR/UV double resonance methods as well as chirped-pulse Fourier transform microwave spectroscopy in combination with quantum-chemical computations yield the energetically preferred monomer and cluster geometries. Furthermore, the complex internal dynamics of the diphenylether monomer and the one-water clusters are analysed. In the cluster with three water molecules, water forms a cyclic structure similar to the isolated water trimer. The interactions ruling the structures of the higher-order water clusters are a combination of the ones identified for the two monohydrate isomers, with dispersion being a decisive contribution for systems that have a delicate energetic balance between different hydrogen-bonded arrangements of similar energy.

Structural analyses of isolated cyclic tetrapeptides with varying amino acid residues.

Cyclic peptides represent a large class of substances that occur in nature with important biological and medical functions. Synthetic cyclic peptides are used as artificial receptors due to a series of advantages over conventional receptors. In order to optimize their binding abilities, investigations of their intrinsic structural properties especially with regard to the influence of different amino acid residues are fundamental. Here we report the structural analysis of two synthetic cyclic tetrapeptides cyclo[l-Tyr(Me)-d-Pro-l-Ala-d-Pro] (CPAla) and cyclo[l-Tyr(Me)-d-Pro-l-Glu(Me)-d-Pro] (CPGlu) in a molecular beam by means of combined IR/UV spectroscopic techniques. Structural assignments were achieved by comparing experimentally obtained vibrations and harmonically calculated frequencies including dispersion corrections (B3LYP-D3/TZVP). The investigated cyclic peptides contain an arrangement of an amino acid sequence which is no longer symmetric compared to the former investigations of the cyclo[l-Tyr(Me)-d-Pro]2 peptide. It turns out that all investigated compounds prefer conformations stabilized by two internal hydrogen bonds. In the case of CPGlu containing a flexible side chain with a terminal hydrogen bond acceptor an additional structure was observed in which a hydrogen bond between the terminal carboxylate group and a ring NH group is formed.

Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol.

BACKGROUND AND OBJECTIVE: Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites. METHODS: Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol. RESULTS: When depolarizing pulses to 0 mV were started from a holding potential of -70 mV, half-maximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 mumol for thymol and 376 and 571 mumol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant Kd for thymol and menthol from the inactivated state was 22 and 106 mumol for the neuronal and 23 and 97 mumol for the skeletal muscle sodium channel, respectively. CONCLUSIONS: The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.