N-long-chain monoacylated derivatives of 2,6-diaminopyridine with antiviral activity

N-Monoacyl-2,6-diaminopyridines (2a-c) and N,N'-diacyl-2,6-diaminopyridines (3a-c) were synthesized from 2,6-diaminopyridine by acylation with the corresponding acyl halide or by dehydration with the corresponding carboxylic acid using 1,3-dicyclohexylcarbodiimide (DCC). The antiviral activities of N-monoacyl- and N,N'-diacyl-2,6-diaminopyridines (2a-c and 3a-c) were estimated using plaque reduction assay with HSV-1. All N-monoacyl derivatives (2a-c) showed significant anti-herpes simplex virus (HSV)-1 activity (EC(50) = 15.3-18.5 microg/ml). The CC(50) values of 2a-c measured using Vero cells ranged at 37.5-50.0 microg/ml. These compounds showed no significant antibacterial activities with Escherichia coli or Staphylococcus aureus even at a concentration of 1 mg/ml. The N,N'-diacyl derivatives (3a-c) showed no significant anti-HSV-1 activity.     

Analysis of nucleotides by pressure-assisted capillary electrophoresis-mass spectrometry using silanol mask technique

A method for the determination of nucleotides based on pressure-assisted capillary electrophoresis-electrospray ionization mass spectrometry (PACE-MS) is described. To prevent multi-phosphorylated species from adsorbing onto the fused-silica capillary, silanol groups were masked with phosphate ions by preconditioning the capillary with the background electrolyte containing phosphate. During preconditioning, nebulizer gas was turned off to avoid contamination of MS detector with phosphate ions. To detect nucleotides using the CE positive mode at a pH 7.5, it was necessary to apply air pressure to the inlet capillary during electrophoresis to supplement the electroosmotic flow (EOF) toward the cathode. Moreover, we exchanged the running electrolyte every analysis using the buffer replenishment system to obtain the required reproducibility. Under the optimized conditions, 14 phosphorylated species such as nucleotides, nicotinamide-adenine dinucleotides and coenzyme A (CoA) compounds were well determined in less than 20 min. The relative standard deviations (n=6) of the method were better than 0.9% for migration times and between 1.7% and 8.1% for peak areas. The detection limits for these species were between 0.5 and 1.7 micromol/L with pressure injection of 50 mbar for 30 s (30 nL) at a signal-to-noise ratio of 3. This approach is robust and quantitative compared to the previous method, and its utility is demonstrated by the analysis of intracellular nucleotides and CoA compounds extracted from Escherichia coli wild type, pfkA and pfkB knockout mutants. The methodology was used to suggest that pfkA is the main functional enzyme.     

Synthesis and applications of novel fluorinated dendrimer-type copolymers by the use of fluoroalkanoyl peroxide as a key intermediate

Fluoroalkanoyl peroxide reacted with 1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane (TTRV-Si) to afford fluoroalkyl end-capped oligomers containing some unreacted vinyl segments under very mild conditions. Fluoroalkyl end-capped cyclosiloxane oligomers containing some vinyl segments thus obtained reacted with N,N-dimethylacrylamide and fluoroalkanoyl peroxide to afford new fluorinated dendrimer-type block copolymers in good isolated yield. Similar reactions were also occurred by the use of 1,3,5-trivinyl-1,3,5-trimethylcyclotrisiloxane instead of TTRV-Si, and the corresponding fluorinated dendrimer-type block copolymer was obtained in good isolated yield. These fluorinated dendrimer-type block copolymers had an excellent solubility not only in water but also in traditional organic solvents including aliphatic fluorinated solvents. Interestingly, these fluorinated block copolymers were found to form the self-assembled dendrimer-type polymeric aggregates in aqueous solutions. More interestingly, these fluorinated block copolymers had an extremely higher dispersion ability of not only single-walled carbon nanotube and fullerenes but also magnetic nanoparticles into water, compared to that of the corresponding two fluoroalkyl end-capped oligomers.     

Synthesis of 10-nm scale oligothiophene molecular wires bearing anchor units at both terminal positions

Oligothiophenes with the length of ca.10 nm bearing anchor units (a protected thiol group or trimethylsilylethynyl) at both terminal positions in the conjugated backbone have been synthesized by the block-coupling synthetic strategy. Their electronic properties were clarified by spectroscopic and electrochemical measurements.     

Highly emissive pi-conjugated alkynylpyrene oligomers: their synthesis and photophysical properties

We newly prepared para- and meta-linked alkynylpyrene oligomers and examined their photophysical properties. Oligomerization of monomeric building blocks was performed by CuI-promoted oxidative coupling reaction. The resulting oligomers mainly consist of 2-mer to 6-mer that were assigned on the basis of MALDI-TOF mass spectra, and the 2-mer, 3-mer, and 4-mer were isolated and fully characterized. From their absorption and fluorescence spectra, the para-linked oligomers were found to be somewhat pi-conjugated compared with meta-linked ones, and the fluorescence quantum yields decreased with increasing oligomer length (Phif = 0.79-0.55).     

Synthesis of dimethyl gloiosiphone a by way of palladium-catalyzed domino cyclization

The synthesis of a spiro[4.4]nonane skeleton by the palladium-catalyzed domino cyclization of a linear 7-methylene-2,10-undecadienyl acetate is described. The pi-allylpalladium intermediate underwent intramolecular alkene insertion with high intraannular diastereoselectivity, followed by intramolecular Heck-type cyclization, leading to a spiro[4.4]nonane system. Oxidation of the allylic ether moiety and transformation of the vinyl group to an exo-methylene unit provided 3, which is the known synthetic intermediate of dimethyl gloiosiphone A (2).     

Time-resolved in situ ATR-IR observations of the process of sorption of water into a poly(2-methoxyethyl acrylate) film

A process of water sorption into a biocompatible polymer, poly(2-methoxyethyl acrylate) (PMEA), was investigated by time-resolved, in situ, attenuated total reflection infrared spectroscopy. Evidence for three different types of hydrated water in PMEA, that is, nonfreezing water, freezing bound water, and freezing water, were found. Each hydration structure was elucidated at the functional group level. Nonfreezing water, which never crystallizes, even at -100 degrees C, has a C=O...H-O type of hydrogen bonding interaction with the carbonyl group of PMEA. Freezing bound water, which crystallizes in a heating process below 0 degrees C, interacts with the methoxy moiety in the PMEA side chain terminal. Freezing water, which crystallizes approximately 0 degrees C, has bulk-water-like structure with an O-H...O-H hydrogen bonds network. It has been concluded from the present study that the methoxy moiety in the PMEA side chain terminal plays an important role for the excellent biocompatibility of PMEA.     

Numerical methods for conjunctive two‐dimensional surface and three‐dimensional sub‐surface flows

Sophisticated catchment runoff problems necessitate conjunctive modeling of overland flow and sub‐surface flow. In this paper, finite difference numerical methods are studied for simulation of catchment runoff of two‐dimensional surface flow interacting with three‐dimensional unsaturated and saturated sub‐surface flows. The equations representing the flows are mathematically classified as a type of heat diffusion equation. Therefore, two‐ and three‐dimensional numerical methods for heat diffusion equations were investigated for applications to the surface and sub‐surface flow sub‐models in terms of accuracy, stability, and calculation time. The methods are the purely explicit method, Saul'yev's methods, the alternating direction explicit (ADE) methods, and the alternating direction implicit (ADI) methods. The methods are first examined on surface and sub‐surface flows separately; subsequently, 12 selected combinations of methods were investigated for modeling the conjunctive flows. Saul'yev's downstream (S‐d) method was found to be the preferred method for two‐dimensional surface flow modeling, whereas the ADE method of Barakat and Clark is a less accurate, stable alternative. For the three‐dimensional sub‐surface flow model, the ADE method of Larkin (ADE‐L) and Brian's ADI method are unconditionally stable and more accurate than the other methods. The calculations of the conjunctive models utilizing the S‐d surface flow sub‐model give excellent results and confirm the expectation that the errors of the surface and sub‐surface sub‐models interact. The surface sub‐model dominates the accuracy and stability of the conjunctive model, whereas the sub‐surface sub‐model dominates the calculation time, suggesting the desirability of using a smaller time increment for the surface sub‐model. Copyright © 2000 John Wiley & Sons, Ltd.     

p-Nitrophenol permeability and temperature characteristics of an acryloyl-L-proline methyl ester-based porous gel membrane

Thermoresponsive porous gel membranes were synthesized by a simultaneously occurring process consisting of radiation-induced polymerization and crosslinking in aqueous solutions at various concentrations of acryloyl-L -proline methyl ester(A-ProOMe) without a crosslinker. Permeation of p-nitrophenol (PNP) through a thermoresponsive porous gel membrane obtained at a monomer concentration of 80% (w/w) drastically reduced around 14°C, the lower critical solution temperature (LCST) of linear poly(A-ProOMe) in water, from 0.60 × 10⁻³ cm/min at 10°C to no permeation at 18°C, accompanied by changes in both size and shape of pores associated with gel shrinkage. Moreover, it was found that porous gel membranes with a porosity of approximately 60% had a greater PNP permeability constant through porous gel membranes with mutually connected pores obtained at a monomer concentration of 50% (w/w) than individually supported pores obtained at a monomer concentration of 70% (w/w). © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1495–1500, 1998