Hyperpolarized 13C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in vivo Study

Hyperpolarized [1-¹³C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1-¹³C]fumarate metabolism using parahydrogen-induced polarization (PHIP), a low-cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost-effective and high-yield synthetic pathway of hydrogenation precursor [1-¹³C]acetylenedicarboxylate (ADC) was developed. The trans-selectivity of the hydrogenation reaction of ADC using a ruthenium-based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set-up was used to generate hyperpolarized [1-¹³C]fumarate at sufficient ¹³C polarization for ex vivo detection of hyperpolarized ¹³C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo ¹³C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.     

Phase structure of a U(1) lattice gauge theory with dual gauge fields

We introduce a U(1) lattice gauge theory with dual gauge fields and study its phase structure. This system is partly motivated by unconventional superconductors like extended s-wave and d  -wave superconductors in the strongly-correlated electron systems and also studies of the t–J$t\text{–}J$ model in the slave-particle representation. In this theory, the “Cooper-pair” (or RVB spinon-pair) field is put on links of a cubic lattice due to strong on-site repulsion between original electrons in contrast to the ordinary s  -wave pair field on sites. This pair field behaves as a gauge field dual to the U(1) gauge field coupled with the hopping of electrons or quasi-particles of the t–J$t\text{–}J$ model, holons and spinons. By Monte Carlo simulations we study this lattice gauge model and find a first-order phase transition from the normal state to the Higgs (superconducting) phase. Each gauge field works as a Higgs field for the other gauge field. This mechanism requires no scalar fields in contrast to the ordinary Higgs mechanism. An explicit microscopic model is introduced, the low-energy effective theory of which is viewed as a special case of the present model.     

2′,4′-BNA/LNA with 9-(2-Aminoethoxy)-1,3-diaza-2-oxophenoxazine Efficiently Forms Duplexes and Has Enhanced Enzymatic Resistance**

Artificial nucleic acids are widely used in various technologies, such as nucleic acid therapeutics and DNA nanotechnologies requiring excellent duplex-forming abilities and enhanced nuclease resistance. 2′-O,4′-C-Methylene-bridged nucleic acid/locked nucleic acid (2′,4′-BNA/LNA) with 1,3-diaza-2-oxophenoxazine (BNAP ( B^H )) was previously reported. Herein, a novel B^H analogue, 2′,4′-BNA/LNA with 9-(2-aminoethoxy)-1,3-diaza-2-oxophenoxazine (G-clamp), named BNAP-AEO ( B^AEO ), was designed. The B^AEO nucleoside was successfully synthesized and incorporated into oligodeoxynucleotides (ODNs). ODNs containing B^AEO possessed up to 10⁴-, 152-, and 11-fold higher binding affinities for complementary (c) RNA than those of ODNs containing 2′-deoxycytidine ( C ), 2′,4′-BNA/LNA with 5-methylcytosine ( L ), or 2′-deoxyribonucleoside with G-clamp ( P^AEO ), respectively. Moreover, duplexes formed by ODN bearing B^AEO with cDNA and cRNA were thermally stable, even under molecular crowding conditions induced by the addition of polyethylene glycol. Furthermore, ODN bearing B^AEO was more resistant to 3′-exonuclease than ODNs with phosphorothioate linkages.     

Robust Inclusion Complexes of Crown Ether Fused Tetrathiafulvalenes with Li+@C60 to Afford Efficient Photodriven Charge Separation

Inclusion complexes of benzo‐ and dithiabenzo‐crown ether functionalized monopyrrolotetrathiafulvalene (MPTTF) molecules were formed with Li⁺@C₆₀ ( 1? Li⁺@C₆₀ and 2? Li⁺@C₆₀). The strong complexation has been quantified by high binding constants that exceed 10⁶ M ^?1 obtained by UV/Vis titrations in benzonitrile (PhCN) at room temperature. On the basis of DFT studies at the B3LYP/6‐311G(d,p) level, the orbital interactions between the crown ether moieties and the π surface of the fullerene together with the endohedral Li⁺ have a crucial role in robust complex formation. Interestingly, complexation of Li⁺@C₆₀ with crown ethers accelerates the intersystem crossing upon photoexcitation of the complex, thereby yielding ³(Li⁺@C₆₀)*, when no charge separation by means of ¹Li⁺@C₆₀* occurs. Photoinduced charge separation by means of ³Li⁺@C₆₀* with lifetimes of 135 and 120 μs for 1? Li⁺@C₆₀ and 2? Li⁺@C₆₀, respectively, and quantum yields of 0.82 in PhCN have been observed by utilizing time‐resolved transient absorption spectroscopy and then confirmed by electron paramagnetic resonance measurements at 4 K. The difference in crown ether structures affects the binding constant and the rates of photoinduced electron‐transfer events in the corresponding complex.     

Identification of Site-Specific Degradation in Bacterially Expressed Human Fibroblast Growth Factor 4 and Generation of an Aminoterminally Truncated,Stable Form

Fibroblast growth factor 4 (FGF4) is considered as a crucial gene for tumorigenesis in humans and the development of mammalian embryos. The secreted, mature form of human FGF4 is thought to be comprised of 175 amino acid residues (proline³² to leucine²⁰⁶, Pro³²-Leu²⁰⁶). Here, we found that bacterially expressed, 6× histidine (His)-tagged human FGF4 (Pro³²-Leu²⁰⁶) protein, referred to as HishFGF4, was unstable such as in phosphate-buffered saline. In these conditions, site-specific cleavage, including between Ser⁵⁴ and Leu⁵⁵, in HishFGF4 was identified. In order to generate stable human FGF4 derivatives, a 6× His-tagged human FGF4 (Leu⁵⁵-Leu²⁰⁶), termed HishFGF4L, was expressed in Escherichia coli. HishFGF4L could be purified from the supernatant of cell lysates by heparin column chromatography. In phosphate-buffered saline, HishFGF4L was considered as sufficiently stable. HishFGF4L exerted significant mitogenic activities in mouse embryonic fibroblast Balb/c 3T3 cells. In the presence of PD173074, an FGF receptor inhibitor, the growth-stimulating activity of HishFGF4L disappeared. Taken together, we suggest that HishFGF4L is capable of promoting cell growth via an authentic FGF signaling pathway. Our study provides a simple method for the production of a bioactive human FGF4 derivative in E. coli.     

Construction of Helically Stacked π-Electron Systems in Poly(quinolylene-2,3-methylene) Stabilized by Intramolecular Hydrogen Bonds

π-Stacked polymers, which consist of layered π-electron systems in a polymer, can be expected to be used in molecular electronic devices. However, the construction of a stable π-stacked structure in a polymer is considerably challenging because it requires sophisticated designs and precise synthetic methods. Herein, we present a novel π-stacked architecture based on poly(quinolylene-2,3-methylene) bearing alanine derivatives as the side chain, obtained through the living cyclo-copolymerization of an o-allenylaryl isocyanide. In the resulting polymer, the neighboring quinoline rings of the main chain form a layered structure with π–π interactions, which is stabilized by intramolecular hydrogen bonds. The vicinal quinoline units form two independent helices and the whole molecule is a twisted-tape structure. This structure is established on the basis of UV/CD spectra, theoretical calculations, and atomic-force microscopy.     

Mechanical and tribological properties of DLC coatings deposited by plasma-based ion implantation and deposition method on polyoxymethylene

Polyoxymethylene (POM, polyacetal) is one of the most popular plastics for machine elements, especially in Japan. However, it is difficult to use it under severe operating conditions such as high speed and high contact pressure. Diamond-like carbon (DLC) coatings were well known to be tribological and functional coatings. However, both POM and DLC coatings are difficult to adhere them each other. In the present paper, DLC coatings are deposited by plasma-based ion implantation and deposition (PBIID) method on POM substrate, and validity of DLC coatings on POM was investigated through friction and mechanical tests. When gas pressure was 0.2 and 0.8 Pa, hardness and adhesion properties of DLC coating deposited under gas pressure of 0.5 Pa were lower compared with under 0.2 and 0.8 Pa. For preparing DLC coatings having hard and good adhesion properties, relatively thin substrate was suitable. A correlation between relative humidity in the laboratory and friction coefficient was confirmed while DLC coatings remain on the substrate.     

Silaboration of [1.1.1]Propellane: A Storable Feedstock for Bicyclo[1.1.1]pentane Derivatives

The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive‐free conditions. The silaborated BCP can be obtained on a gram‐scale in a single step without the need for column‐chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C?B/C?Si bonds on the BCP scaffold, including development of a modified Suzuki–Miyaura cross‐coupling reaction at the highly sterically hindered bridgehead sp³ carbon center of the BCP skeleton using a combination of highly activated BCP boronic esters, copper(I) oxide, and a PdCl₂(dppf) catalyst system.     

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.