Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic ethers and evaluation of the interaction with transmembrane proteins

Ladder-shaped polyether (LSP) toxins represented by brevetoxins and ciguatoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic systems, based on the convergent method via alpha-cyano ethers. The ALPs possessing the simple iterative structure with different numbers of rings would be useful for structure-activity relationship studies on the molecular length, which is supposed to be important when naturally occurring LSPs elicit their toxicity. Two series of ALPs were prepared to evaluate the hydrophilic or hydrophobic effects of the side chains: (i) both sides were functionalized as diols (A series), and (ii) one side remained as diol and the other side was protected as benzyl ethers (B series). To examine the interaction of these ALPs with TM proteins, dissociation of glycophorin A (GpA) dimers into monomers was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The heptacyclic ether (ALP7B) elicited the most potent activity in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited an intriguing phenomenon to induce precipitation of GpA in a dose-dependent manner, under the low concentration of SDS (0.03%). ALP10A also induced precipitation of integrin alpha 1beta 1, a TM protein known to form heterodimers in the lipid bilayer membranes. The different activities among the ALPs can be accounted for by the concept of "hydrophobic matching" that is, lengths of the hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25 A, which match the lengths of the hydrophobic region of alpha-helical TM proteins, as well as the hydrophobic thickness of lipid bilayer membranes. The concept of the hydrophobic matching would be a clue to understanding the interaction between LSPs and TM proteins, and also a guiding principle to design ALPs possessing potent affinities with TM proteins.     

Transport properties of CdIn2S4 single crystals

Several transport properties have been studied on CdIn₂S₄ singlê crystals with different degrees of deviation from stoichiometry. The energy gap at 0 K was determined from the electrical measurements to be 2.2 eV. The anisotropy of the magnetoresistance effect was found and it was suggested that the minima of the conduction band were located at points along the [100] directions in k space. From an analysis of the mobility data it was found that the high resistivity of the samples is due to compensation of donors by acceptors introduced by excess sulphur. Several band parameters, the carrier scattering mechanisms and the impurity levels were determined. The thermal conductivity was measured from 4 K to 300 K and analysed by Callaway's formalism.     

Semiconducting properties of CuIn5S8 single crystals I. Electrical properties

The electrical resistivity and Hall coefficient of n-type CuIn₅S₈ single crystals were measured in the temperature range from 80 K–500 K. The energy gap at 0 K was determined to be 1.4 eV. The donor levels at 0.017 eV and 0.09 eV below the conduction band are identified. The mobility data are analysed assuming scatterings by acoustic and polar optical phonons and ionized impurities.     

Analysis of ice water by the thermally stimulated depolarized current (TSDC) method.

The thermally stimulated depolarized current and temperature profiles (TSDC analysis) on iced water was proved to be an effective tool for the qualitative evaluation of various water samples, each having an independent relaxation process, brought about by a pure dipolar orientation. The method proved to be applicable to different kinds of water samples used in the experiment and tap-water samples from different suppliers. Five main peaks (A to E, in the order of increasing temperature) were observed, of which two peaks (B and D) were found for the first time. The appearance of multiple peaks suggested the existence of multi-states of the hydrogen bond, cleaved by the TSDC process. The TSDC profiles were quite reproducible when the water samples contained practically no cations. A separate addition of each cation at a low concentration level revealed that a cation with a smaller ionic radius shifted peak A to a higher temperature. For ice of tap water, which contained relatively higher amount of cations, the TSDC profiles were quite different in shape compared with the standard ice-water samples (shift of peaks A - D to higher temperature, and a strong increase in the current strength of peaks B - E). However, it was still possible to tell from which districts the water samples were supplied.     

Convenient synthesis of porphine

Porphine formation from pyrrole and formaldehyde was examined in detail. Under optimized conditions, 9 mg of crystalline porphine was obtained per 1 ml of pyrrole.     

Synthesis and reaction of 2-imino-1,3-thiazetidines and 2-imino-1,3-dithietanes

2-Imino-1,3-thiazetidines and 2-imino-1,3-dithietanes were synthesized and their reactivities were studied. The former readily underwent ring-opening reaction with amines to yield guanidine derivatives. The reaction products were applied to the synthesis of heterocycles such as triazoles and triazines. The latter was converted to isothiocyanate by the reaction of m-chloroperbenzoic acid.     

Temperature variation of piezoelectric moduli in oriented poly(γ-methyl L-glutamate)

The real and imaginary components of the complex piezoelectric strain constant, which relates the polarization to the applied stress, have been determined for elongated films of poly(γ-methyl L -glutamate) over the temperature range ?170°C to +170°C at a frequency of 20 Hz. The variation of the piezoelectric constant with temperature is similar for both α-helical and β-form molecular conformations. The sign of piezoelectric polarization is opposite for L and D polymers. A simple model, representing the piezoelectric crystallites as embedded in nonpiezoelectric amorphous regions, is proposed to account for the piezoelectric temperature dispersion curves.     

Photoelectron spectra of nitrophenols and nitroanisoles

Photoelectron spectra (PES) of nitrophenols and nitroanisoles were measured and interpreted with the aid of previously reported PES of nitrobenzene, phenol and anisole. The effect of the intramolecular hydrogen bond is discussed in the case of o-nitrophenol.     

Electrochemical, HPLC and electrospray ionization mass spectroscopic analyses of peroxycitric acid coexisting with citric acid and hydrogen peroxide in aqueous solution

We successfully determined the molecular structure of peroxycitric acid (PCA) coexisting in the aqueous equilibrium mixture with citric acid (CA; 1,2,3-tricarboxylic-2-hydroxy propane) and hydrogen peroxide (H₂O₂) by a combined use of reversed-phase HPLC (RP-HPLC), potentiometric, hydrodynamic chronocoulometric (HCC) and electrospray ionization mass spectroscopic (ESI-MS) methods. Firstly, the RP-HPLC was employed to separate CA, PCA and H₂O₂ coexisting in the equilibrium mixture and the concentration of CA consumed (ΔC_CA) in the formation of PCA that was evidenced to be fairly stable during the RP-HPLC measurement was quantitatively measured based on the standard calibration curve of CA. Secondly, the total oxidant concentration (C_Ox) corresponding to peroxycarboxylic (–COOOH) group in PCA in the equilibrium mixture was determined using potentiometric measurement. The ratio of C_Ox/ΔC_CA was found to be 1.07, which indicates that only one –COOH group in CA molecule is oxidized to the corresponding –COOOH group in PCA molecule. Thirdly, using the HCC technique the diffusion coefficient of PCA, which could be electroreduced at a more positive potential by 1.0 V than the coexisting H₂O₂, was independently measured as 0.3 × 10⁻⁵ cm² s⁻¹ and at the same time, by considering ΔC_CA as the concentration of PCA, the number of electrons (n) required for the reduction of PCA was determined to be 2. The result obtained from RP-HPLC and HCC, i.e., n = 2 which is equivalent to one –COOOH group in PCA, is in agreement with that obtained from the combination of RP-HPLC and potentiometric measurements. Finally, the structure of PCA was proposed to contain one –COOOH group with a molecular mass of 208 confirmed by negative ion ESI-MS method. A probable molecular structure of PCA was discussed.