Synthesis of rhodium–carbonyl complexes bearing a novel P,N-chelating ligand of Schiff-base type

Schiff-base type N,P-chelating ligands, phosphorus analogues of imino–anilido ligands, were designed and synthesized as a new type of ligands toward transition metals, and the rhodium–carbonyl complexes bearing the novel imino–phosphido and phosphaalkenyl-anilido ligands were synthesized as stable crystalline compounds. Their structures were definitively revealed by X-ray crystallographic analysis, showing the unique electronic features of the ligands. In addition, the effective trans-influence of the phosphorus atom was suggested on the basis of the structural parameters and spectroscopic features of the isolated complexes.     

Charged lepton contributions to bipair neutrino mixing

The bipair neutrino mixing describes the observed solar and atmospheric mixings; however, it predicts vanishing reactor mixing angle, which is inconsistent with the observed data. We explore the ways of minimally modifying the bipair neutrino mixing by including charged lepton contributions. There are two categories of the bipair neutrino mixing which are referred to as case 1 and case 2. It turns out that, without arbitrary phases, a minimal modification is realized by just considering one e–τ$e\text{–}\tau$ contribution from the charged lepton sector in the case 1. On the other hand, not only e–τ$e\text{–}\tau$ contribution but also μ–τ$\mu \text{–}\tau$ contribution is required to realize a minimal modification in the case 2.     

Therapeutic targets in the ASK1-dependent stress signaling pathways

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.     

Acid-catalyzed copolymerization of aspartic acid with ω-amino acid. -Biodegradability and Ca2+ chelating ability of poly(aspartic acid -Co- ω-amino acid)-

The polycondensation of L-aspartic acid (1) with various ω-amino acids (2) using phosphoric acid catalyst produced poly(succinimide-co-ω-amino acid)s (3), which was followed by alkali hydrolysis to poly(aspartic acid-co-ω-amino acid) (4). The Ca²⁺ chelating abilities of 4 depended on the content of comonomer unit in the copolymer and on the kind of amino acids. For the copolymer using 11-aminoundecanoic acid (2d) as a comonomer, the Ca²⁺ chelating ability was higher than that of poly(sodium acrylate). For poly(aspartic acid-co-6-aminocaproic acid) (4c), there was a tendency to increase according to the increase of 6-aminocaproic acid (2c) unit in the copolymer. The biodegradability of the copolymer in the case of 2c as a comonomer, evaluated by TOC measurement, was 63%, which was the highest degradability among the copolymers having different methylen length. The biodegradability of 4c decreased with increasing the 2c unit in 4c.     

Human serum albumin incorporating synthetic hemes as an O2-carrying hemoprotein: control of O2-binding ability by heme structure

Incorporation of different structured synthetic hemes, 5,10,15,20-tetraphenylporphyrinatoiron(II) derivetives with a covalently linked proximal base [FeP( 1 ) to FeP( 7 )], into human serum albumin (HSA), provides seven types of albumin-heme hybrids (HSA-FeP) with different O₂-binding abilities. An HSA host absorbs a maximum of eight FeP molecules in each case. The obtained all HSA-FePs can reversibly bind and release O₂ under physiological conditions (in aqueous media, pH 7.3, 37°C) as similar as hemoglobin and myoglobin. The difference in the fence structures did not affect the O₂-binding parameters, however the axial histidine coordination significantly increased the O₂-binding affinity, which is ascribed to the low O₂-dissociation rate constants. The most remarkable effect of the heme structure appeared in the half-lifetime (τ_1/2) of the O₂-adduct complex. The dioxygenated rHSA-FeP( 4 ) showed an unusually long lifetime (τ_1/2: 25 hr at 37°C) which is ca. 13-fold longer than that of rHSA-FeP( 1 ).     

Oxygen-carrying plasma hemoprotein “albumin-heme”: nitric oxide binding and physiological responses after administration in vivo

Recombinant human serum albumin complexed with tetraphenylporphinatoiron(II) derivative, “albumin-heme (rHSA-FeP)”, is a synthetic oxygen (O₂)-carrying plasma hemoprotein, which becomes a new class of red blood cell substitute. The UV-vis. absorption and ESR spectroscopy revealed that rHSA-FeP formed six-coordinate nitrosyl complex after exposure of nitric oxide (NO) gas. Although the NO-binding affinity of rHSA-FeP (P_1/2^NO: 1.7 × 10⁻⁶ Torr, pH 7.3, 25°C) is 9-fold higher compared to that of hemoglobin (Hb), the administration of this artificial hemoprotein solution into anesthetized rat does not induce an acute increase in blood pressure (hypertension), which is often observed in Hb-based O₂-carriers due to the depletion of NO (endothelial derived relaxing factor).     

Synthesis and radical polymerization of end-methacrylated poly(succinimide) leading to poly(aspartic acid) hydrogel

The polycondensation of aspartic acid in the presence of phthalic anhydride was carried out in mesitylene/sulfolane using o-phosphoric acid as a catalyst. The polymer yields were 91–78%, when 5–20 mol-% phthalic anhydride was added into the feed. The obtained poly(succinimide) carried a phthalic imide unit and a succinic acid unit as end groups. In the MALDI-TOF mass spectrum, the peak-to-peak distances between adjacent signals were 97.07 m/z, corresponding to the calculated value (97.07) of the succinimide unit. Poly(succinimide) was reacted with 2-(methacryloxy)ethyl isocyanate to give end-methacrylated poly-(succinimide), in which the end-functionality of the methacrylate group was ca. 1. End-methacrylated poly-(succinimide) was polymerized with ethylene glycol dimethacrylate using 2,2′-azoisobutyronitrile to give poly(succinimide) gel, which could be converted into water-absorbing poly(aspartic acid) hydrogel.