Dual Chemical Modification of a Polytheonamide Mimic: Rational Design and Synthesis of Ion‐Channel‐Forming 48‐mer Peptides with Potent Cytotoxicity

Polytheonamide B ( 1 ) is a natural peptide that displays potent cytotoxicity against P388 mouse leukemia cells (IC₅₀=0.098 nm ). Linear 48‐mer 1 is known to form monovalent cation channels on binding to lipid bilayers. We previously developed a fully synthetic route to 1 , and then achieved the design and synthesis of a structurally simplified analogue of 1 , namely, dansylated polytheonamide mimic 2 . Although the synthetically more accessible 2 was found to emulate the channel function of 1 , its cytotoxicity was decreased 120‐fold. Herein, the chemical preparation and biological evaluation of seven analogues 3 – 9 of 2 are reported. Compounds 3 – 9 were modified at their N terminus and/or the side chain of residue 44 of 2 to alter their physicochemical properties. The total synthesis of 3 – 9 was accomplished in a unified fashion by a combination of solid‐phase and solution‐phase chemistry. Systematic evaluation of the hydrophobicities, single‐channel currents, ion‐exchange activities, and cytotoxicities of 3 – 9 revealed that their hydrophobicities are correlated with the total magnitude of ion exchange and determine their cytotoxic potency. Consequently, the most hydrophobic analogue 9 exhibited the lowest IC₅₀ value, which is comparable to that of 1 . Therefore, these results clarified that the bioactivity of the polytheonamide‐based peptides can be rationally controlled by changing their hydrophobicity at the N and C termini of the 48‐amino‐acid sequence.     

Improvement of spatial homogeneity in GdBCO/IBAD-MgO coated conductor

Recent process optimization allows improving homogeneity and a significant increase of J_c in GdBa₂Cu₃O_7-δ deposited on ion-beam assisted deposited MgO template (GdBCO/IBAD-MgO). We applied low-temperature laser scanning microscopy and laser scanning thermo-electric microscopy (LSTEM) to investigate local dissipation and defects simultaneously in recent GdBCO/IBAD-MgO coated conductor. By using high-resolution LSTEM, we could detect current blocking obstacles which are responsible for the large scale local dissipation. Data on the present GdBCO/IBAD-MgO coated conductors point out a significant reduction of current blocking obstacles compared to the previous process. We have shown the improvement of spatial homogeneity in the recent GdBCO/IBAD-MgO coated conductors. Current blocking obstacles are much less densely distributed as compared to previous YBCO/IBAD-GZO coated conductor. Obstacles larger than several micrometer significantly increase local dissipation whereas smaller defects do not influence it noticeably. 2D map of the phase delay component of the thermoelectric voltage lock-in signal is effective to analyze current blocking obstacles having action upon local dissipation.     

Solution properties,unperturbed dimensions,and chain flexibility of poly(1‐adamantyl acrylate)

Poly(1‐adamantyl acrylate) (PAdA) exhibits much higher glass transition and degradation temperatures than other polyacrylates. However, the quantitative evaluation of the stiffness of this polymer chain has not been reported previously. In this study, the dilute solution properties and conformational characteristics of PAdA were evaluated using viscometry and scattering techniques. The unperturbed dimensions of this polymer were evaluated using the Burchard–Stockmayer–Fixman extrapolation and the touched‐bead wormlike chain model. The PAdA chain has a comparable persistence length, diameter per bead and characteristic ratio to poly(methyl methacrylate) and polystyrene. All these results indicate that PAdA is less flexible than common polyacrylates. In addition, the second virial coefficients (A₂) of PAdA in different solvents obtained by static light scattering were compared. Among the solvents investigated, tetrahydrofuran is a moderate solvent. Radius of gyration of a polymer sample in the various solvents ranged from 16.8 to 30.3 nm. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1526–1531     

Copolymerization of Carbon Dioxide and Epoxide: Functionality of the Copolymer

Carbon dioxide and epoxide copolymerize in the presence of some organometallic catalyst systems under moderate conditions to give aliphatic polycarbonates of high molecular weight. Some metalloporphyrins of aluminum and zinc were found to act as novel catalysts for the polymerization of epoxide and for the copolymerization of carbon dioxide and epoxide, though not alternating. The polymers are characterized by the narrow molecular weight distribution and the unusual stereoregularity. Starting from the copolymerization of carbon dioxide and trimethylsilyl glycidyl ether with diethylzinc-water catalyst system, a readily degradable polycarbonate having hydroxyl group was obtained.     

From Living to “Immortal” Polymerization

Aluminum porphyrin is an excellent initiator for the living polymerizations of a wide variety of monomers such as epoxide, β-lactone, δ-lactone, ε-lactone, and lactide, and also for the alternating copolymerization of epoxide and cyclic acid anhydride or carbon dioxide, to give polymers and copolymers with narrow molecular weight distribution. Aluminum porphyrin was recently found to initiate also the living polymerization of methacrylic ester. In the polymerizations of epoxides and lactones initiated with aluminum porphyrin in the presence of an appropriate protic compound, polymers with narrow molecular weight can be obtained with the number of the polymer molecules more than those of the initiator. This fact demonstrates the “immortal” nature of the polymerization due to unusual reactivities of aluminum prophyrin.     

Index Abstracts

Abstract

Calorimetric titrations have been performed in anhydrous acetonitrile at 25°C to give the complex stability constants (K _s) and the thermodynamic parameters (ΔGΔ, ΔHΔ and ΔSΔ) for the complexation of light lanthanoid(III) nitrates (La-Gd) with N-benzylaza-21-crown-7 3. Data analyses, assuming 1:1 stoichiometry, were successfully applied to all light lanthanoid-azacrown ether combinations employed. Using the present and previous data on 15- to 21- membered N-benzylazacrown ethers 1–3, the effect of ring size upon complexation behavior was discussed comparatively and globally from the thermodynamic point of view. The complexation behaviors are analyzed in terms of the size-fit concept, N-substituent coordination numbers, and lanthanoid's surface charge density. Thermodynamically the complexation of light lanthanoids with azacrown ethers is enthalpy-driven, while the cation selectivity is generally entropy-driven in acetonitrile.     

Helicity Control in the Preparation of Chiral Co-crystals from Tryptamine and Achiral Carboxylic Acids by Pseudo-seeding

Abstract

Chiral crystals of tryptamine and achiral carboxylic acids such as p-chlorobenzoic acid, cinnamic acid, p-chlorocinnarnic acid and p-methylcinnamic acid were prepared by crystallization from the solutions of both components. All the crystals belonged to typical chiral space group P2₁2₁2₁. The crystal chirality is generated through the formation of a unidirectional twofold helix between the two components through quaternary ammonium salt interaction and hydrogen bonding in the lattice. This kind of spontaneous crystallization necessarily gives crystals of both clockwise and counterclockwise helicites. Here, pseudo-seeding based on utilizing these crystals as seed crystals was examined, resulting in successful helicity control in crystallization from solutions of tryptamine and different carboxylic acids.     

Effect of Non‐Specifically Adsorbed Ions on the Surface Oxidation of Pt(111)

The oxidation processes of a Pt(111) electrode in alkaline electrolytes depend on non‐specifically adsorbed ions according to in situ X‐ray diffraction and infrared spectroscopic measurements. In an aqueous solution of LiOH, an OH_ad adlayer is formed in the first oxidation step of the Pt(111) electrode as a result of the strong interaction between Li⁺ and OH_ad, whereas Pt oxidation proceeds without OH_ad formation in CsOH solution. Structural analysis by X‐ray diffraction indicates that Li⁺ is strongly protective against surface roughening caused by subsurface oxidation. Although Cs⁺ is situated near the Pt surface, the weak protective effect of Cs⁺ results in irreversible surface roughening due to subsurface oxidation.     

A novel derivatization reagent possessing a bromoquinolinium structure for biological carboxylic acids in HPLC‐ESI‐MS/MS

A novel bromoquinolinium reagent, i.e. 1‐(3‐aminopropyl)‐3‐bromoquinolinium bromide (APBQ), was synthesized for the analysis of carboxylic acids. A simple and practical precolumn derivatization procedure using the APBQ in RP chromatography and MS (HPLC‐MS) has been developed using bile acids and free fatty acids, as the representative carboxylic acids in biological samples. The APBQ efficiently reacted with carboxylic acids at 60°C for 60 min in the presence of N,N‐dicyclohexylcarbodiimide and pyridine as the activation reagents. Because the APBQ possesses a bromine atom in the structure, the identification of a series of carboxylic acids was easily achieved due to the characteristic bromine isotope pattern in the mass spectra. The APBQ also has a quaternary amine structure, thus the positively charged derivatives are predominate for the highly sensitive detection of carboxylic acids. The APBQ was successfully applied to the selective determination of biological carboxylic acids in human plasma. The bile acids (chenodeoxycholic acid and deoxycholic acid) and several saturated (stearic acid and palmitic acid) and unsaturated free fatty acids (oleic acid and linoleic acid) were reasonably determined by HPLC‐MS under the proposed procedure. Based on the results of analyses of human plasma and saliva, the proposed procedure using APBQ seems to be applicable for the qualitative and quantitative analyses of a series of carboxylic acids in biological samples.