Liquid chromatographic determination of penicillins by postcolumn degradation with sodium hypochlorite using an hollow-fibre membrane reactor

A sensitive, high-performance liquid chromatographic method involving postcolumn degradation with sodium hypochlorite and using a hollow-fibre membrane as a reactor is described for the determination of penicillins. Penicillins were separated on a C18 column followed by postcolumn reaction with sodium hypochlorite and sodium hydroxide using aminated and sulphonated hollow-fibre membrane reactors immersed in each solution, and detected at 270-280 nm based on the UV absorbances of the degradation products. At penicillin concentrations of 2 micrograms/ml, the precisions (relative standard deviation) were 2.28-4.78%. The detection limits of the proposed method were 2.5-25 ng for each penicillin at a signal-to-noise ratio of 3. Ampicillin and its metabolites [(5R,6R)-ampicilloic acid, the (5S,6R)-epimer and (2R)-pierazine-2',5'-dione] in human serum and urine were simultaneously determined by this method.     

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.     

Hydrogels of poly(hydroxyethyl methacrylate) and hydroxyethyl methacrylate—glycerol monomethacry-late copolymers

Hydrophilic three-dimensional polymer networks (hydrogels) were prepared from hydroxyethyl methacrylate (HEMA) and the copolymer HEMA and glycerol monomethacrylate (GMMA). The equilibrium water content of the hydrogels in water was investigated as a function of the initial dilution of the polymerization mixture, the type of solvent, and the hydrophilicity of the polymer. The initial dilution was found to have a decisive effect on the swelling or deswelling of hydrogels after the completion of the gel formation. With relatively less hydrophilic hydrogels, there is a critical initial dilution to produce the gel which does not swell or deswell in water after the gel formation. This “isovolumic” initial dilution shifts toward a higher dilution as the hydrophilicity of the hydrogels increases; however, when hydrophilicity of the polymer rises above a certain point, gels always swell in water. Permeability of oxygen through hydrogels was also studied.     

New asymmetric reactions of 2-formyl- and 2-acyl-1-[(2,4, 6-triisopropylphenyl)sulfinyl]naphthalenes via diastereomeric rotamers

Nucleophilic reactions with Grignard reagents and the Mukaiyama aldol reactions of the naphthaldehydes having the (2,4, 6-triisopropylphenyl)sulfinyl group produced products with high stereoselectivity. In these reactions, the stereochemistry of the major products changes depending on the Lewis acids used. Reduction of the 2-acyl-1-[(2,4,6-triisopropylphenyl)sulfinyl]naphthalenes also proceeds with high stereoselectivity but with a different stereochemistry depending on the reducing agents. We have demonstrated, by the mechanistic consideration based on the X-ray crystal structures as well as the (1)H and (13)C NMR spectral data, that the extremely high and specific stereoselectivities of these reactions are due to the predominant rotamer around the C(naph)-S axis. Synthesis of enantiomerically pure 2-naphthylmethanol is provided as an example.     

Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a general methodology for the synthesis of potent and selective mGluR2/3 agonists

[Chemical reaction: See text] A Et3Al mediated intramolecular epoxide opening, cyclopropanation reaction is described. The transformation provided highly functionalized bicyclo[3.1.0]hexane systems in high efficiency and with perfect H or F endo selectivity. Application of this reaction to the synthesis of mGluR2/3 agonist 1 (43% overall yield) and a few intermediates suitable for the synthesis of other bicyclo[3.1.0]hexane mGluR2/3 agonists is discussed.     

Rhodamine B amine as a highly sensitive fluorescence derivatization reagent for saccharides in reversed-phase liquid chromatography

6-Rhodamine B amine functions as a highly sensitive fluorescence derivatization reagent for mono- and oligosaccharides; it reacts with the reducing end of saccharides under acidic conditions. The fluorescent derivatives of five monosaccharides can be separated within 25 min by reversed-phase liquid chromatography with isocratic elution. The detection limits (S/N = 3) for mono-, di-, and oligosaccharides are 7-51, 13, and 9-35 fmol/20 microl injection, which correspond to analyte concentrations of 35-255, 65, 45-175 nM, respectively. We have applied this derivatization method successfully to the analysis of the components of oligosaccharides in glycoproteins (ribonuclease B and fetuin) following their acidic or enzymatic hydrolysis. The results from these analyses are in good agreements with the reported values established previously.     

Antioxidant activity and Neurite outgrowth-enhancing activity of scorbamic acid and a red pigment derived from ascorbic acid

Abstract

L-Ascorbic acid (AA), known as vitamin C, can form browning products by a non-enzymatic process during storage and the browning products cause deterioration of agricultural products. In the browning reaction, a red pigment, 2,2´-nitrilodi-2(2´)-deoxy-L-ascorbic acid ammonium salt (NDA), is generated from AA via L-scorbamic acid (SCA) as an intermediate. However, the biological activities of SCA and NDA have not yet been clarified. In this study, we assayed the antioxidant activities of SCA and NDA using ABTS radical cation and their neurite outgrowth-enhancing activities in PC12 cells. SCA showed stronger radical-scavenging activity than that of AA, while NDA hardly showed any activity. SCA and NDA enhanced the neurite outgrowth induced by dibutyryl cyclic AMP after their incorporation into cells in the same manner as that of AA. The results indicated that SCA has antioxidant activity and that SCA and NDA have neurite outgrowth-enhancing activity.     

Screening method for organic aciduria by spectrofluorometric measurement of total dicarboxylic acids in human urine based on intramolecular excimer-forming fluorescence derivatization

A simple screening method of organic aciduria by spectrofluorometric measurement of total dicarboxylic acids in human urine is described. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butanoic acid hydrazide (PBH). Dicarboxylic acids in urine were converted to the corresponding dipyrene-labeled derivatives by reaction with PBH in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and pyridine, and the derivatives afforded intramolecular excimer fluorescence (420-540 nm) which can clearly be discriminated from the normal fluorescence (360-420 nm) emitted from reagent blanks. The technique is so selective that it permits spectrofluorometric measurement of total amount of dicarboxylic acids by the direct derivatization of diluted urine samples. The same reaction mixture has also served as a liquid chromatographic (LC) sample for the separative determination of individual dicarboxylic acids. The spectrofluorometric data did not contradict with the LC data. These methods were usefully applied to preliminary screening test of glutaric aciduria. In conclusion, the present derivatization method allows rapid and direct determination of total amount of dicarboxylic acids in human urine samples.     

Synthesis and spectroscopic analysis of tetraphenylporphyrinatoantimony(V) complexes linked to boron-dipyrrin chromophore on axial ligands

Tetraphenylporphyrinatoantimony(V) complexes, linked to boron-dipyrrin chromophores on axial ligands, were synthesized. The fluorescence spectra of 1a, 1b and 1c (3-[4-(N,N′-difluorobornyl-5-dipyrrinyl)phenyl]propoxo(methoxo)antimony(V) tetraphenylporphyrin bromide (1a); 6-[4-(N,N′-difluorobornyl-5-dipyrrinyl)phenyl]hexyloxo(methoxo)antimony(V) tetraphenylporphyrin bromide (1b); bis{3-[4-(N,N′-difluorobornyl-5-dipyrrinyl)phenyl]propoxo}antimony(V) tetraphenylporphyrin bromide (1c)) were analyzed under the excitations of N,N′-difluorobornyl-5-dipyrrinylphenyl (Bdpy) and tetraphenylporphyrinatoantimony(V) (Sb(TPP)) chromophores. Under the irradiation of Bdpy chromophore, the excitation energy was transferred from Bdpy chromophore to the Sb(TPP) moiety at 0.13–0.40 of the quantum yields, even in a polar solvent. On the other hand, the emission of Sb(TPP) chromophores was quenched by Bdpy chromophores at rate constants of 10⁸–10⁹ s⁻¹, independent of on the solvent polarity. Under the excitation of the Bdpy chromophore of 1d (3-[4-(N,N′-difluorobornyl-5-dipyrrinyl)phenyl]propoxo(phenyloxo)antimony(V) tetraphenylporphyrin bromide) involving both the Bdpy and the phenoxy chromophores on the axial ligands, the excited singlet state of the Sb(TPP) chromophore generated by the energy transfer from the Bdpy chromophore was quenched by the phenoxy ligand via non-radiative processes involving electron transfer. However, rapid back electron-transfer may occur because no absorption of the anion radical of Sb(TPP) was observed by nanosecond laser photolysis.