PEGylation of an artificial O2 and CO receptor: synthesis, characterisation and pharmacokinetic study

A synthetic oxygen (O(2)) and carbon monoxide (CO) receptor (hemoCD) composed of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(ii) and a per-O-methylated β-cyclodextrin dimer with a pyridine linker (Py3CD) was functionalised with poly(ethylene glycol) (PEG) to elongate the circulation time of the receptor in the bloodstream. α-PEG monocarboxylic acid (HOOC(CH(2))(3)(CO)O-PEG(mw)-OCH(3); mw = 750 or 5k) or α,ω-PEG dicarboxylic acid (HOOC(CH(2))(3)(CO)O-PEG(mw)-O(CO)(CH(2))(3)COOH; mw = 10k or 20k) was reacted with the amino group of 5-(4-aminophenyl)-10,15,20-tris(4-sulfonatophenyl)porphyrin to afford a porphyrin monomer having a PEG chain or a porphyrin dimer having a PEG linker, respectively. The ferrous complexes of these PEGylated porphyrins (PEG750-, PEG5k-, PEG10k- and PEG20k-hemoCDs) bound O(2) in aqueous solution, P(1/2) values being 6.5-8.1 Torr at pH 7.0 and 25 °C. Each PEG(mw)-hemoCD was infused into the femoral vein of a Wistar male rat. After 6 h of the infusions, 67, 82, 86 and 42% of PEG750-, PEG5k-, PEG10k- and PEG20k-hemoCD were excreted in the urine. PEG750-hemoCD with a hydrodynamic diameter (D(h)) of 3.4 nm seemed to partly leak from the blood vessels (pore size: 2-6 nm) before renal filtration (pore size: 4-14 nm). PEG5k- (D(h) = 6.2 nm) and PEG10k-hemoCDs (9.0 nm) hardly passed through the blood vessels but were fully filtered by the kidney, resulting in high excretion rates. A considerable amount of PEG20k-hemoCD (D(h) = 12.0 nm) was retained in the blood even at 6 h after administration. The present study demonstrates that the behaviour of hemoCD in blood after administration can be controlled by modification of hemoCD with PEG having an appropriate molecular weight.     

Effects of the acceptor conjugation length and composition on the electrical memory characteristics of random copolyimides

Resistive‐switching memories based on copolyimides (coPIs), PI‐NTCDIX and PI‐BTCDIX , with different compositions of 4,4′‐diamino‐4″‐methyltriphenylamine ( AMTPA ), 4,4′‐(hexafluoroisopropylidene)diphthalic anhydride, and N,N′‐bis‐(4‐aminophenyl)‐1,8:4,5‐naphthalenetetracarboxydiimide ( NTCDI ) or N,N′‐bis‐(4‐aminophenyl)‐1,2:4,5‐benzenetetracarboxydiimide ( BTCDI ) have been developed. By varying the feed ratio of monomers, PI‐NTCDIX and PI‐BTCDIX showed tunable optical and electronic properties through the charge transfer (CT) between AMTPA and NTCDI or BTCDI . The memory devices based on PI‐NTCDIX exhibited the tunable electrical bistability from the volatile dynamic random access memory to nonvolatile write once read many memory characteristics as the NTCDI composition increased. The OFF/ON electrical switching transition was mainly attributed to the CT mechanism for the charge separated high conductance, based on the analysis of model compounds and density functional theory calculation. Also, the volatility of the memory device depended on the stability of CT complex. The long conjugation and high electron affinity of the NTCDI moiety stabilized the radical anion generated in the CT complex and prevented the recombination of segregated radical species even through applying the high positive or negative voltage. On the other hand, the memory devices based on PI‐BTCDIX showed a rather unique behavior compared with those based on PI‐NTCDIX . At the low BTCDI composition, the device exhibited volatile memory property. However, no switching behavior was observed at the high BTCDI composition due to the low highest occupied molecular orbital energy level of BTCDI . Combining these results and our previous study on perylenebisimide ( PBI ), we concluded that memory characteristics could be tailored by changing the conjugation length ( PBI > NTCDI > BTCDI ) and the acceptor composition in random coPIs. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Metallation of aliphatic carbon atoms: II,syntheses and characterization of the cyclopalladated complexes of N,N-dimethylneopentylamine

N,N-Dimethylneopentylamine reacts with Pd(MeCO₂)₂ to give a novel trinuclear cyclopalladated complex [Me₂NCH₂CMe₂CH₂Pd(μ-MeCO₂)₂Pd(μ-MeCO₂)₂PdCH₂CMe₂CH₂NMe₂]?-0.5C₆H₆ (I). The reaction of I with PPh₃ affords both trans-[Pd(MeCO₂)₂(PPh₃)₂] (II) and [Pd(CH₂CMe₂CH₂NMe₂)(MeCO₂)(PPh₃)] (III). The reaction of III with LiCl yields a mononuclear cyclopalladated complex, [Pd(CH₂CMe₂CH₂NMe₂)Cl(PPh₃)] (IV).     

Open-sandwich immunoassay for sensitive and broad-range detection of a shellfish toxin gonyautoxin

At present, the analytical method for paralytic shellfish poisoning (PSP) toxins in shellfish is the mouse bioassay (MBA), which is an official method of the Association of Analytical Communities (AOAC [8]). However, the low sensitivity and concerns over the number of live animals required for testing have been cited as the major reason for seeking its replacement. In this report, we employed an open-sandwich immunoassay (OS-IA) to detect gonyautoxin (GTX2/3), a kind of PSP toxins. OS-IA, which utilizes the antigen-induced enhancement of antibody V_H/V_L interaction, can measure a small molecule antigen in a noncompetitive format. Hence it has a wider working range and shorter measurement time. We isolated anti-GTX2/3 antibody gene from a hybridoma GT-13A by screening a Fab-displaying phage library. Then the vectors for OS-IA were constructed, and examined for antigen concentration-dependency of the V_H/V_L interaction by OS-ELISA. As a result, in each case, signal intensity increases notably in a wide concentration range (0.1 to >1000 ng mL⁻¹) of free GTX2/3, which was enough to cover its regulation value (80 μg 100 g⁻¹) in many countries. So OS-IA will be widely applicable to detect PSP toxins in shellfish meats and in drinking water.     

A Selective Synthesis of 3,3-Di-C-(hydroxymethyl)-3-deoxy-furanorono-1,4-lactone in the Formose Reaction

Abstract

The formose reaction, by which a complex mixture of sugars and sugar alcohols (the so-called formose) are produced by the base-catalyzed condensation of formaldehyde, has received much attention in connection with the prebiotic synthesis of carbohydrates² and the microbial utilization of formose.^3–5 Formose, however, has not been useful yet, because of the complexity of this product mixture (Fig. 1a). Therefore, it seemed desirable to make the reaction more selective.     

First Synthesis of DL-2-C-Hydroxymethyl-3-Pentulose in the Formose Reaction

Abstract

The formose reactions² in N,N-dimethylformamide (DMF) catalyzed by 2-(dimethylamino)ethanol and thiamine hydrochloride, have been found to give rise to dihydroxyacetone and DL-glycero-tetrulose selectively at 1.1 M and 3.0 M of formaldehyde concentration, respectively. In our consecutive study on the formose reaction in DMF, it has been fortunately found that the distribution of products is able to be controlled by the amount of water added to the reaction mixture. We describe herein the first example of the favored formation of DL-2-C-hydroxymethyl-3-pentu-lose (GP-19¹) in the formose reaction using DMF-H₂O solvent, and it's isolation and structure elucidation.     

Characterization of phase transition of Ba2-xSrxIn2O5 by thermal analysis and high temperature X-ray diffraction

The phase transitions of Ba_2-xSr_xIn₂O₅ were investigated with various thermal analyses and high-temperature X-ray diffraction. It was clarified that crystal structure of Ba_2-xSr_xIn₂O₅ with x=0.0~0.4 varies from brownmillerite through distorted perovskite to another distorted perovskite with increase of temperature. The phase transition from brownmillerite to distorted perovskite was revealed to be first order, whereas transition from distorted perovskite to another one was second order. The specimen with x≥0.5 showed only one first order phase transition from brownmillerite to distorted perovskite. The phase diagram of Ba_2-xSr_xIn₂O₅ was established and existence of tricritical point at ~1100°C with x=0.4~0.5 was suggested. This revised version was published online in August 2006 with corrections to the Cover Date.     

Tritium concentration in fresh,brackish and sea-water samples in Rokkasho-Village,Japan, bordered by nuclear fuel cycle facilities

Summary In order to identify the concentration of tritium (³H) in areas of fresh, brackish and sea water, bordered by nuclear fuel facilities at Rokkasho-Village, Aomori, Japan, water samples were collected from 2001 to 2004 at six points in those areas. Concentration ranges of tritium in fresh river water, brackish lake and seawater samples were 0.60 to 1.1 Bq^. l^-1(mean value 0.79 Bq^. l^-1), 0.20 to 0.87 Bq^. l^-1(mean value 0.41 Bq^. l^-1), and 0.08 to 0.25 Bq^. l^-1(mean value 0.15 Bq^. l^-1), respectively. Relationships between tritium concentrations and salinity in the samples showed a clear negative correlation. Moreover, the seasonal variation of tritium in water from Rokkasho-Village was high in spring and low in fall.     

Synthesis of planar-chiral paracyclophanes via samarium(II)-catalyzed intramolecular pinacol coupling

[reaction: see text] A series of [n]paracyclophanediols (n = 8-12) was synthesized by samarium-catalyzed pinacol coupling for their ansa-bridge formation. Enantiomerically pure [n]paracyclophane esters were derived from the diols in a several steps via chiral resolution (for n = 10) or via crystallization-induced asymmetric transformation (for n = 11) by using amino alcohol auxiliaries and their selective cleavages.