Suitable acid groups and density in electrolytes to facilitate proton conduction.

Proton conducting materials suffer from low proton conductivity under low-relative humidity (RH) conditions. Previously, it was reported that acid-acid interactions, where acids interact with each other at close distances, can facilitate proton conduction without water movement and are promising for overcoming this drawback [T. Ogawa, H. Ohashi, T. Tamaki and T. Yamaguchi, Chem. Phys. Lett., 2019, 731, 136627]. However, acid groups have not been compared to find a suitable acid group and density for the interaction, which is important to experimentally synthesize the material. Here, we performed ab initio calculations to identify acid groups and acid densities as a polymer design that effectively causes acid-acid interactions. The evaluation method employed parameters based on several different optimized coordination interactions of acids and water molecules. The results show that the order of the abilities of polymer electrolytes to readily induce acid-acid interactions is hydrocarbon-based phosphonated polymers > phosphonated aromatic hydrocarbon polymers > perfluorosulfonic acid polymers ≈ perfluorophosphonic acid polymers > sulfonated aromatic hydrocarbon polymers. The acid-acid interaction becomes stronger as the distance between acids decreases. The preferable distance between phosphonate moieties is within 13 Å.

Temperature-induced recovery of a bioactive enzyme using polyglycerol dendrimers: correlation between bound water and protein interaction.

Enzyme application has gained importance over the past decade in bioprocess, biomedical, and pharmaceutical fields. We found that polyglycerol dendrimers (PGDs), which are biocompatible molecules, can recover alcohol dehydrogenase (ADH) from aqueous solution under elevated temperature. A low concentration of PGD (5 wt.%) is sufficient for the recovery of high enzymatic activity, although a high concentration (25-75 wt.%) of glycerol is generally required to stabilize ADH. The enzymatic activity of ADH in suspension with PGDs is over 60% but it is only 10% in that with glycerol. The results of osmolarity and spin-lattice relaxation time (T1) of water measurements in the presence of PGDs suggest that increased amounts of bound water to PGD molecules trigger aggregation along with the direct interaction with ADH. PGDs therefore represent good potential additives for direct recovery of enzymes from aqueous solutions.

Landscape of Research Areas for Zeolites and Metal-Organic Frameworks Using Computational Classification Based on Citation Networks.

The field of porous materials is widely spreading nowadays, and researchers need to read tremendous numbers of papers to obtain a "bird's eye" view of a given research area. However, it is difficult for researchers to obtain an objective database based on statistical data without any relation to subjective knowledge related to individual research interests. Here, citation network analysis was applied for a comparative analysis of the research areas for zeolites and metal-organic frameworks as examples for porous materials. The statistical and objective data contributed to the analysis of: (1) the computational screening of research areas; (2) classification of research stages to a certain domain; (3) "well-cited" research areas; and (4) research area preferences of specific countries. Moreover, we proposed a methodology to assist researchers to gain potential research ideas by reviewing related research areas, which is based on the detection of unfocused ideas in one area but focused in the other area by a bibliometric approach.

Reduction of Dinitrogen to Ammonia Catalyzed by Molybdenum Diamido Complexes.

[Ar2N3]Mo(N)(O-t-Bu), which contains the conformationally rigid pyridine-based diamido ligand, [2,6-(ArNCH2)2NC5H3]2- (Ar = 2,6-diisopropylphenyl), can be prepared from H2[Ar2N3], butyllithium, and (t-BuO)3Mo(N). [Ar2N3]Mo(N)(O-t-Bu) serves as a catalyst or precursor for the catalytic reduction of molecular nitrogen to ammonia in diethyl ether between -78 and 22 °C in a batchwise manner with CoCp*2 as the electron source and Ph2NH2OTf as the proton source. Up to ∼10 equiv of ammonia can be formed per Mo with a maximum efficiency in electrons of ∼43%.

Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

Differentiating Grotthuss proton conduction mechanisms by nuclear magnetic resonance spectroscopic analysis of frozen samples.

Available methods to analyze proton conduction mechanisms cannot distinguish between two proton-conduction processes derived from the Grotthuss mechanism. The two mechanistic variations involve structural diffusion, for which water movement is indispensable, and the recently proposed "packed-acid mechanism," which involves the conduction of protons without the movement of water and is typically observed in materials consisting of highly concentrated (packed) acids. The latter mechanism could improve proton conductivity under low humidity conditions, which is desirable for polymer electrolyte fuel cells. We proposed a method with which to confirm quantitatively the packed-acid mechanism by combining (2)H and (17)O solid-state magic-angle-spinning nuclear magnetic resonance (MAS-NMR) measurement and (1)H pulsed-field gradient (PFG)-NMR analysis. In particular, the measurements were performed below the water-freezing temperature to prevent water movement, as confirmed by the (17)O-MAS-NMR spectra. Even without water movement, the high mobility of protons through short- and long-range proton conduction was observed by using (2)H-MAS-NMR and (1)H-PFG-NMR techniques, respectively, in the composite of zirconium sulfophenylphosphonate and sulfonated poly(arylene ether sulfone) (ZrSPP-SPES), which is a material composed of highly concentrated acids. Such behavior contrasts with that of a material conducting protons through structural diffusion or vehicle mechanisms (SPES), in which the peaks in both (2)H and (17)O NMR spectra diminished below water-freezing temperature. The activation energies of short-range proton movement are calculated to be 2.1 and 5.1 kJ/mol for ZrSPP-SPES and SPES, respectively, which indicate that proton conduction in ZrSPP-SPES is facilitated by the packed-acid mechanism. Furthermore, on the basis of the mean-square displacement using the diffusivity coefficient below water-freezing temperature, it was demonstrated that long-range proton movement, of the order of 1.3 µm, can take place in the packed-acid mechanism in ZrSPP-SPES.

Non-humidified proton conduction between a Lewis acid-base pair.

Proton conduction in zirconium sulphate (ZrSO4) composed of a Lewis acid-base pair was studied. ZrSO4 exhibits non-humidified proton conductivity, comparable to other proton conductors under similar conditions. Ab initio calculation shows that a proton transfers in ZrSO4 from a Lewis acid to a Lewis base without a proton carrier.

A novel, bio-reducible gene vector containing arginine and histidine enhances gene transfection and expression of plasmid DNA.

We have engineered a novel, non-viral, multifunctional gene vector (STR-CH(2)R(4)H(2)C) that contained stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH(2)R(4)H(2)C can form a stable nano-complex with plasmid DNA (pDNA) based on electronic interactions and disulfide cross linkages. In this study, we evaluated the efficacy of STR-CH(2)R(4)H(2)C as a gene vector. We first determined the optimal weight ratio for STR-CH(2)R(4)H(2)C/pDNA complexes. The complexes with a weight ratio of 50 showed the highest transfection efficacy. We also examined the transfection efficacy of STR-CH(2)R(4)H(2)C/pDNA complexes with or without serum and compared STR-CH(2)R(4)H(2)C/pDNA transfection efficacy with that of Lipofectamine. Even in the presence of serum, STR-CH(2)R(4)H(2)C showed higher transfection efficacy than did Lipofectamine. In addition, we determined the mechanism of transfection of the STR-CH(2)R(4)H(2)C/pDNA complexes using various cellular uptake inhibitors and evaluated its endosomal escape ability using chloroquine. Macropinocytosis was main cellular uptake pathway of STR-CH(2)R(4)H(2)C/pDNA complexes. Our results suggested that STR-CH(2)R(4)H(2)C is a promising gene delivery system.

Disulfide crosslinked stearoyl carrier peptides containing arginine and histidine enhance siRNA uptake and gene silencing.

The siRNA has been expected to apply for several diseases such as cancer since siRNA specifically silences the disease-associated genes. However, effective gene carriers should be developed to overcome the low siRNA stability in vivo, form stable complexes and facilitate intracellular uptake of siRNA. In this study, to develop a safe and efficient siRNA carrier, stearoyl (STR) peptides with Cys (C), Arg (R), and His (H) residues that can form disulfide cross linkages via Cys (C) were synthesized, and their suitability as siRNA carriers was evaluated. The particle size of STR-CH(2)R(4)H(2)C/siRNA complexes was about 100 nm. The cellular uptake ability after transfection with FAM-siRNA with STR-CH(2)R(4)H(2)C, CH(2)R(4)H(2)C, or STR-GH(2)R(4)H(2)G was significantly higher than that with FAM-siRNA only. STR-CH(2)R(4)H(2)C showed the highest cellular uptake ability when compared with CH(2)R(4)H(2)C and STR-GH(2)R(4)H(2)G. STR-CH(2)R(4)H(2)C did not induce substantial cytotoxicity. The intratumor injection of STR-CH(2)R(4)H(2)C/vascular endothelial growth factor (VEGF) siRNA (siVEGF) complexes achieved a high anti-tumor effect in tumor bearing mice. These results suggest STR-CH(2)R(4)H(2)C has potential of effective siRNA carrier possible to exercise silencing effect in vitro and in vivo.