PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery

An A-B-C type triblock copolymer, tandemly aligning two types of polycations with different pKa values in a single polymer strand, was developed for the construction of novel polyplex micelles, satisfying a high DNA condensing ability as well as a proton buffering activity directed to elevating gene transfection. The micelle might feature the distinctive three-layered structure, where an inner polyplex layer of condensed pDNA with poly(l-lysine) (pKa approximately 9.4) as the C segment is successively wrapped with an intermediate layer of poly[(3-morpholinopropyl)aspartamide] (B segment) with a comparatively low pKa of approximately 6.2, to provide a buffering effect, and an outer PEG layer (A segment) as a biocompatible palisade.     

Anion binding to a ferric porphyrin complexed with per-O-methylated beta-cyclodextrin in aqueous solution

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphinato iron(III) (Fe(III)TPPS) forms a very stable 1:2 complex with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD), whose iron(III) center is located at a hydrophobic cleft formed by two face-to-face TMe-beta-CD molecules. Various inorganic anions (X(-)) such as F(-), Cl(-), Br(-), I(-), N(3)(-), and SCN(-) coordinate to Fe(III)TPPS(TMe-beta-CD)(2) to form five-coordinate high-spin Fe(III)TPPS(X)(TMe-beta-CD)(2), while no coordination occurs with ClO(4)(-), H(2)PO(4)(-), NO(3)(-), and HSO(4)(-). Except for F(-), none of the anions investigated coordinate to Fe(III)TPPS in the absence of TMe-beta-CD due to extensive hydration to the anions as well as to Fe(III)TPPS. The present system shows a high selectivity toward the N(3)(-) anion. The thermodynamics suggests that Lewis basicity, hydrophilicity, and shape of an X(-) anion are the main factors to determine the stability of the Fe(III)TPPS(X)(TMe-beta-CD)(2) complex.     

Mössbauer study of new vanadate glass with large charge-discharge capacity

Charge-discharge capacity and cyclicity of lithium ion battery (LIB) was evaluated in which 15Li₂O·10Fe₂O₃·xSnO₂·5P₂O₅·(70–x)V₂O₅ glass (x?=?0 and 20 in mol%, abbreviated as xLFSPV) was used as a cathode. A local structure of xLFSPV glass before and after charging was investigated by ⁵⁷Fe- and ¹¹⁹Sn-Mössbauer spectroscopies. ⁵⁷Fe-Mössbauer spectrum of xLFSPV glass with ‘x’ of 20 was composed of a doublet with isomer shift (δ) of 0.35_±0.02 mm s^???1 and quadrupole splitting (Δ) of 0.88_±0.03 mm s^???1 due to distorted Fe^IIIO₄ tetrahedra. ¹¹⁹Sn-Mössbauer spectrum of this glass consisted of a doublet with δ of 0.08_±0.01 and Δ of 0.52_±0.01 mms^???1 due to distorted Sn^VIO₆ octahedra. After discharging the battery from 4.5 to 1.0 V, larger δ of 0.40_±0.03 mm s^???1 and Δ of 0.94_±0.04 mm s^???1 were obtained, indicating that both iconicity of Fe-O bonds and local distortion of Fe^IIIO₄ tetrahedra were increased. On the contrary, identical δ of 0.09_±0.01 mm s^???1 and Δ of 0.50_±0.01 mm s^???1 were observed in the ¹¹⁹Sn-Mössbauer spectrum of 20LFSPV glass after the discharge, indicating that chemical environment of Sn^IVO₆ octahedra was not affected after the discharge. Charge-discharge curve of LIB containing 20LFSPV glass as a cathode active material recorded under the current density of 8.3 mA g^???1 (0.011 mA cm^???2) between 1.0 and 4.5 V showed a large initial charge capacity of 431.1 mAh g^???1 and discharge capacity of 382.3 mAh g^???1, respectively. These results indicate that 20LFSPV glass could be a new cathode active material for LIB.     

Rearrangement of 4,5α-epoxymorphinan derivatives with carbamoylepoxy rings provide novel oxazatricyclodecane structures

We describe the rearrangement of a carbamoylepoxy 4,5α-epoxymorphinan derivative that provided a novel 4,5α-epoxymorphinan derivative with an oxazatricyclodecane structure via an oxabicyclo[2.2.2]octane intermediate. We proposed the mechanism of the rearrangement reaction based on results observed in different deprotonation conditions. Epimerization occurred during rearrangement under reversible, but not irreversible, deprotonation conditions. The rearrangement product had a novel fundamental structure with moderate affinities for opioid receptors (K_i (μ)=47.7 nM, K_i (δ)=174.6 nM, and K_i (κ)=248.1 nM). Thus, the rearrangement products might have high potency as opioid ligands.     

Synthesis of Disaccharide Nucleosides by the O‐Glycosylation of Natural Nucleosides with Thioglycoside Donors

Disaccharide nucleosides constitute an important group of naturally‐occurring sugar derivatives. In this study, we report on the synthesis of disaccharide nucleosides by the direct O‐glycosylation of nucleoside acceptors, such as adenosine, guanosine, thymidine, and cytidine, with glycosyl donors. Among the glycosyl donors tested, thioglycosides were found to give the corresponding disaccharide nucleosides in moderate to high chemical yields with the above nucleoside acceptors using p‐toluenesulfenyl chloride (TolSCl) and silver triflate (AgOTf) as promoters. The interaction of these promoters with nucleoside acceptors was examined by ¹H NMR spectroscopic experiments.     

Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists,Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and β-Arrestin-Mediated Pathways

Opioid receptors (ORs) are classified into three types (μ, δ, and κ), and opioid analgesics are mainly mediated by μOR activation; however, their use is sometimes restricted by unfavorable effects. The selective κOR agonist nalfurafine was initially developed as an analgesic, but its indication was changed because of the narrow safety margin. The activation of ORs mainly induces two intracellular signaling pathways: a G-protein-mediated pathway and a β-arrestin-mediated pathway. Recently, the expectations for κOR analgesics that selectively activate these pathways have increased; however, the structural properties required for the selectivity of nalfurafine are still unknown. Therefore, we evaluated the partial structures of nalfurafine that are necessary for the selectivity of these two pathways. We assayed the properties of nalfurafine and six nalfurafine analogs (SYKs) using cells stably expressing κORs. The SYKs activated κORs in a concentration-dependent manner with higher EC₅₀ values than nalfurafine. Upon bias factor assessment, only SYK-309 (possessing the 3S-hydroxy group) showed higher selectivity of G-protein-mediated signaling activities than nalfurafine, suggesting the direction of the 3S-hydroxy group may affect the β-arrestin-mediated pathway. In conclusion, nalfurafine analogs having a 3S-hydroxy group, such as SYK-309, could be considered G-protein-biased κOR agonists.     

Nanosecond Time-Gated Spectroscopy of Laser-Ablation Plume of Human Hair to Detect Calcium for Potential Diagnoses

We demonstrate the nanosecond time-gated spectroscopy of plume luminescence in UV laser ablation of human hair. Clear and sharp peaks of calcium ion (Ca⁺) appear in the spectrum although the Ca content is only 0.1% in human hair. Highly sensitive detection of Ca is thus possible. In the experiment, the peak intensity of Ca⁺ was measured for human hair samples of female subjects over a wide range of age, and compared to the bone mineral density of the lumbar vertebrae of the subjects themselves. Our experimental results suggest that this specific spectroscopy has the potential for novel diagnoses including monitoring of daily Ca intake and a screening diagnosis of osteoporosis. The spectroscopic system and time transition of plume-luminescence spectra are also described.     

On a Riemann hypothesis analogue for selfdual weight enumerators of genus less than 3

In this contribution the Riemann hypothesis analogue presented by Iwan Duursma is considered. Whether the analogue for a given selfdual code holds depends on its Hamming weight enumerator. A necessary and sufficient condition is provided in the case of genus less than 3 for the homogeneous polynomials in two variables invariant under the MacWilliams transform. Also the case of half integral genus is studied and similar results are obtained.