Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain

Amyloid fibrils have been an important subject as they are involved in the development of many amyloidoses and neurodegenerative diseases. The formation of amyloid fibrils is typically initiated by nucleation, whereas its exact mechanisms are largely unknown. With this situation, we have previously identified prefibrillar aggregates in the formation of insulin B chain amyloid fibrils, which have provided an insight into the mechanisms of protein assembly involved in nucleation. Here, we have investigated the formation of insulin B chain amyloid fibrils under different pH conditions to better understand amyloid nucleation mediated by prefibrillar aggregates. The B chain showed strong propensity to form amyloid fibrils over a wide pH range, and prefibrillar aggregates were formed under all examined conditions. In particular, different structures of amyloid fibrils were found at pH 5.2 and pH 8.7, making it possible to compare different pathways. Detailed investigations at pH 5.2 in comparison with those at pH 8.7 have suggested that the evolution of protofibril-like aggregates is a common mechanism. In addition, different processes of evolution of the prefibrillar aggregates have also been identified, suggesting that the nucleation processes diversify depending on the polymorphism of amyloid fibrils.     

The Effect of Li on Structure of Supported Rh Particles in Zeolite

Abstract

We prepared Rh ion exchanged Y-type zeolite (RhY) and Li-doped RhY (Li/RhY) catalysts and studied the structure transformation of Rh intercalated species during CO adsorption and CO₂ hydrogenation by EXAFS and TEM. We found that Rh particles in RhY initially supported inside the zeolite cage as 1.3 nm spherical or hemispherical particles. CO exposure of the fresh RhY caused formation of atomically dispersed Rh species. After CO₂ hydrogenation and following reduction, the Rh particles aggregated to form 3.3 nm particles on the outer surface. Meanwhile, Rh particles in Li/RhY were embedded in the zeolite cages, which were narrowed by Li deposition on the wall. The size of the Rh particles was 0.8 nm in diameter. The Rh particles in Li/RhY were stable under reduction, CO adsorption, and CO₂ hydrogenation conditions. We concluded Li additive changed the stability of Rh particles in the supercage by modifying surface hydroxyl group concentration.     

Improved Synthesis of ortho-Phenylene-bridged Cyclic Tetrapyrroles and Oxidative Fusion Reactions Toward Substituted Tetraaza[8]circulenes

Hetero[8]circulenes have emerged as novel functionalized heteronanographenes that show various promising functions such as bright fluorescence, charge transporting, and redox reactivities. One of the effective synthetic strategy is the fold-in type oxidative fusion reaction of ortho-phenylene-bridged cyclic tetrapyrroles, whose construction, however, is not well-sophisticated in terms of reproducibility and possibility for versatile derivatization. In this paper, a “reverse” coupling strategy has been developed, which enabled synthesis of opp-type low symmetric analogues of cyclic tetrapyrroles. Oxidative fusion reaction conditions to afford tetraaza[8]circulenes have also been reinvestigated and improved. Substituent effects of cyclic tetrapyrroles and tetrabenzotetraaza[8]circulenes are studied for solid-state structures and packing structures, redox potentials, and optical properties.     

Magnetic Circularly Polarized Luminescence from PtIIOEP and F2-ppyPtII(acac) under North-up and South-up Faraday Geometries

The magnetic circularly polarized luminescence (MCPL) and photoluminescence (PL) spectra of achiral (2,3,7,8,12,13,17,18-octaethylporphyrinato)platinum(II), PtOEP , and [2-(4′,6′-difluorophenyl)pyridinato-N,C^2′]platinum(II) acetylacetonate-O,O, F₂-ppyPt(acac) , in toluene and dichloromethane solutions were recorded under an external magnetic field of 1.6 T with N-up and S-up Faraday geometries. The MCPL signs of PtOEP and F₂-ppyPt(acac) were controlled solely by changing the N-up and S-up geometries. The MCPL/PL wavelengths of F₂-ppyPt(acac) in solutions were varied by the ratio of the monomeric and excimeric species.     

Synthesis and Properties of Spiro-double Sila[7]helicene: The LUMO Spiro-conjugation

A double helicene with a spiro-Si linker ( 4 ) was synthesized by four successive nucleophilic substitutions on SiCl₄. Its (P,P), (M,M) and (P,M) isomers were isolated and characterized by single crystal X-ray analysis. Due to the central spirosilabi[fluorene] moiety, the two helicene units in 4 are symmetrically and nearly perpendicularly arranged. (P,P)- 4 and (M,M)- 4 exhibit unique optical properties attributable to the LUMO spiro-conjugation between the two sila[7]helicene units.     

1,3,9-Triaza-2-oxophenoxazine: An Artificial Nucleobase Forming Highly Stable Self-Base Pairs with Three AgI Ions in a Duplex

Metal-mediated base pairs (MMBPs) formed by natural or artificial nucleobases have recently been developed. The metal ions can be aligned linearly in a duplex by MMBP formation. The development of a three- or more-metal-coordinated MMBPs has the potential to improve the conductivity and enable the design of metal ion architectures in a duplex. This study aimed to develop artificial self-bases coordinated by three linearly aligned Ag^I ions within an MMBP. Thus, artificial nucleic acids with a 1,3,9-triaza-2-oxophenoxazine (9-TAP) nucleobase were designed and synthesized. In a DNA/DNA duplex, self-base pairs of 9-TAP could form highly stable MMBPs with three Ag^I ions. Nine equivalents of Ag^I led to the formation of three consecutive 9-TAP self-base pairs with extremely high stability. The complex structures of 9-TAP MMBPs were determined by using electrospray ionization mass spectrometry and UV titration experiments. Highly stable self-9-TAP MMBPs with three Ag^I ions are expected to be applicable to new DNA nanotechnologies.     

Synthesis of the Core Oligosaccharides of Lipooligosaccharides from Campylobacter jejuni: A Putative Cause of Guillain–Barré Syndrome

The chemical synthesis of the highly branched core oligosaccharides of lipooligosaccharides (LOSs) found in Campylobacter jejuni, which causes Guillain–Barré syndrome by a preceding infection, is described. The target LOS mimics, consisting of eight or nine monosaccharides, were classified into three groups as key building blocks: ganglioside-core tetra-/pentasaccharides (GM1-/GD1a-like), l -glycero-d -manno-heptose-containing trisaccharides, and 3-deoxy-d -manno-2-octulosonic acid (KDO) residues. These synthetic fragments were obtained from commercially available monosaccharides. Less obtainable l -glycero-d -manno-heptose and KDO residues, as key components of the LOSs, were synthesized from p-methoxyphenyl d -mannoside and di-O-isopropylidene-protected d -mannose, respectively. The synthesis of α-KDO glycoside, as one of the most difficult stereocontrolled glycosidic constructions, was achieved by treating a 2,3-ene derivative of KDO with phenylselenyl trifluoromethanesulfonate as a suitable α-directing reagent. All synthetic blocks were constructed through a convergent synthetic route, which resulted in the first synthesis of structurally challenging LOS core glycans containing ganglioside GM1 and GD1a-core sequences.     

Photoalignmentability of silsesquioxane-containing citraconimide and its solvent-induced surface enrichment in PMMA matrix

Photo-reactive polymer of silsesquioxane-containing citraconimide (SQ-CI) was synthesised and evaluated as a photoalignment layer for polymerisable liquid crystals (PLC). A generation mechanism of the anisotropy by the linearly polarised ultraviolet light was discussed by comparing optical retardation of SQ-CI with theoretical calculations using density functional theory. In addition, the SQ-CI and poly(methyl methacrylate) were blended for a model of unification of photoalignment layer and protection layer in liquid crystal display. The orientation of PLC on the blend film was dominated by the solvent used for the sample preparation of PMMA/SQ-CI blend. We found that the SQ-CI was enriched at surface of the blend film prepared from the ?-butyrolactone solution, while not in the case of the film prepared from cyclopentanone solution. The surface enrichment in the film prepared from ?-butyrolactone solution does not follow the conventional mechanism which is that the lower surface free energy component segregates to the blend surface, because the surface free energy of SQ-CI is higher than that of PMMA. Based on the result of solvent-annealing effect and photoalignmentability, we concluded that the mechanism of surface enrichment was explained due to the difference of affinity between the polymer and the solvent.     

Synthesis of 4′-substituted 2′-deoxy-4′-thiocytidines and its evaluation for antineoplastic and antiviral activities

4′-Azido- (7), 4′-C-fluoromethyl- (8) 4′-C-ethynyl- (9) and 4′-C-cyano- (10) 2′-deoxy-4′-thiocytidines have been synthesized. In this study, it was found that the isolated yield of 4′-thiouracil nucleoside 13 in a Lewis acid-promoted Vorbrüggen-type glycosidation utilizing 12 was better than that of the electrophilic glycosidation reaction between silylated uracil and 11. This improved result prompted us to perform the glycosidation utilizing 36 and 43 for the synthesis of 37 and 44. Introduction of the azido group was carried out by nucleophilic substitution in the 4′-benzoyloxy derivative 22a. On the other hand, 9 and 10 were synthesized by way of the chemical manipulation of the hydroxymethyl group at the 4′-position of 46.Evaluation of the antineoplastic activity of 2 and 7–10 against human B-cell (CCRF-SB) and T-cell leukemia (Molt-4) cell lines revealed that 4′-azido- (7) and 4′-C-fluoromethyl- (8) derivatives exhibited cytotoxic activity whereas no cytotoxicity was observed in the 4′-C-ethynyl- (9) and 4′-C-cyano- (10) derivatives as well as the parent compound 2. Compound 7 was also found to possess promising antiviral activity against VZV and HSV-1 without any cytotoxity against HEL host cells. It is noteworthy that 7 exhibited potent inhibitory activities against the thymidine kinase-deficient (TK^?) mutant of VZV and HSV-1.     

Unprecedented Sequence Control and Sequence-Driven Properties in a Series of AB-Alternating Copolymers Consisting Solely of Acrylamide Units

Herein, we report a method to synthesize a series of alternating copolymers that consist exclusively of acrylamide units. Crucial to realizing this polymer synthesis is the design of a divinyl monomer that contains acrylate and acrylamide moieties connected by two activated ester bonds. This design, which is based on the reactivity ratio of the embedded vinyl groups, allows a “selective” cyclopolymerization, wherein the intramolecular and intermolecular propagation are repeated alternately under dilute conditions. The addition of an amine to the resulting cyclopolymers afforded two different acryl amide units, i.e., an amine-substituted acryl amide and a 2-hydroxy-ethyl-substituted acryl amide in alternating sequence. Using this method, we could furnish ten types of alternating copolymers; some of these exhibit unique properties in solution and in the bulk, which are different from those of the corresponding random copolymers, and we attributed the differences to the alternating sequence.