Lipid bilayer reorganization under extreme pH conditions

Supported lipid bilayers containing phosphatidylcholine headgroups are observed to undergo reorganization from a 2D fluid, lipid bilayer assembly into an array of complex 3D structures upon exposure to extreme pH environments. These conditions induce a combination of molecular packing and electrostatic interactions that can create dynamic morphologies of highly curved lipid membrane structures. This work demonstrates that fluid, single-component lipid bilayer assemblies can create complex morphologies, a phenomenon typically only associated with lipid bilayers of mixed composition.     

Hydrolytic stability of nitrogenous-heteroaryltrifluoroborates under aqueous conditions at near neutral pH

The hydrolytic stability of heteroaryltrifluoroborates under physiological conditions has been analyzed by ¹⁹F NMR spectroscopy and is found to be greatly enhanced by the presence of endocyclic ring nitrogens. Stability is further enhanced by the presence of exocyclic electron withdrawing substituents. As with aryltrifluoroborates, NMR analysis suggests that the hydrolysis proceeds via single rate-determining step reflecting loss of the first fluoride atom. The stability of these complexes is significant both in terms of metal catalyzed cross-coupling reactions as well as the potential for generating boronic acid based ¹⁸F-PET imaging agents.     

A reinvestigated mechanism of ribosylation of adenine under silylating conditions

The mechanism of chemical synthesis of adenosine has been reinvestigated. Depending on the reaction conditions and the presence of N⁶-protecting groups, ribosylation of adenine proceeds via different kinetic products: 3-riboadenine in strongly acidic media, 7-ribosylated derivative in the silyl method, and 1-(β-d-ribofuranosyl)adenine when applying N⁶-acyladenine and silylating conditions.     

Enrichment of adenosine using thermally responsive chromatographic materials under friendly pH conditions

A thermally responsive boronate affinity chromatographic material, which showed thermal sensitivity, had been successfully applied for the enrichment and separation of cis‐diol‐containing compounds, and the capture and release process could be facilitated by adjusting the temperature. However, in this system, the pH of the mobile phase must be higher than 9.8, and alkaline media can lead to the degradation of labile compounds; the use of silica beads also limits its use. In this study, thermally responsive boronate affinity chromatographic material, namely poly(N‐isopropylacrylamide‐co‐N‐acryloyl‐3‐aminophenylboronic acid) grafted silica, was successfully prepared by atom transfer radical polymerization. Its structure was confirmed by IR spectroscopy and the graft ratio was 20.8%, determined by thermogravimetric analysis. Furthermore, the capture/release of adenosine, a cis‐diol, was performed from pH 5.0–9.0 and 10–50°C. The elution of adenosine was remarkably retarded at decreased temperatures and adenosine could be captured completely at 10°C at pH values of 5.0–9.0. The enrichment of adenosine could be achieved by simply changing the temperature from 10 to 50°C. Therefore, this material not only improved the stability of the silica, but was also suitable for the capture of oxidation‐sensitive biological analytes. Moreover, it could be used for the enrichment of cis‐diol‐containing compounds in LC with MS.     

Improved stability of OPALMON tablets under humid conditions. III: Application of the rotary vacuum drying method to dry Opalmon tablets

In stability studies on moisture-resistant Opalmon tablets in press-through-packages (PTP), which were placed in aluminum bags, we found that the degradation rate of the dextran formulation is faster than that of the lactose formulation. The fast degradation of the dextran formulation is attributed to residual moisture in the package because drying the tablets before packaging suppressed the degradation and there is a good correlation between the stability of the drug and the water-activity of the tablets. Therefore, we developed a new drying method for the tablets, i.e. the rotary vacuum drying method, and investigated the effects of the operating conditions such as heating temperature, rotation speed, and vacuum degree on the drying time, and the appearance of the tablets. Using the rotary vacuum drying method, the tablets were dried over a short time (30 min) on a mass production scale so that the water activity was less than 0.03. Furthermore, the tablets suffered negligible damage such as breaking and chipping during the drying process. These results indicate that the rotary vacuum drying method is useful for drying tablets on mass production scales.     

Analysis of degradation mechanism of plasticized PVC under artificial aging conditions

A plasticized poly(vinyl chloride) (PVC) has the advantage of low cost, long-term stability and flame resistance among other commodity plastic, and has been in service as a product in railway field. However, the transition of the plasticizer concentration through the degrading condition and its relationship with the mechanical properties, the molecular motion, the appearance of surface and other properties was not clear. These relationships were studied by means of Rheovibron, pulse NMR, GC/MS, GPC, SEM and other methods. The bulk properties show similar change between weathering and thermal aging. In addition, the molecular chain was little influenced, however, the plasticizer concentration shows obviously different transition through each phase of aging conditions. According to the results of the observation of surface and section, different appearances between weathering and thermal aging were indicated and these appearances closely relate to the bulk properties. In conclusion, through the weathering condition, a stepwise flow out of inorganic components and plasticizer was presumable to be a main mechanism of the degradation. On the other hand, through the thermal aging condition, the rearrangement and aggregation of the molecular chain by the annealing effect were conceivable as the main mechanism of the degradation.     

Development and validation of high-performance liquid chromatography method for determination of clarithromycin in pharmaceutical tablets

Clarithromycin is a very important macrolide antibiotic used to treat bacterial infections in human and veterinary medicine. This study reports the development and validation of cost-effective, simple, precise, accurate, and robust high-performance liquid chromatography (HPLC) for the determination of clarithromycin (CLA) in tablets. Reversed-phase chromatography was conducted using a standard column at 55°C with ultraviolet detection at 215 nm. A mobile phase consisting of acetonitrile –2-methyl-2-propanol –potassium phosphate buffer was used at a flow rate of 1.0 mL/min. The proposed method displayed good linearity, precision, accuracy, robustness, and specificity. The present HPLC was compared with capillary electrophoresis and bioassay methods and the results indicated that there was no significant difference between these methods. Moreover, the obtained results demonstrated the validity of the isocratic HPLC, which allows reliable quantitation of CLA in pharmaceutical samples. Thus, it can be used as a substitute alternative methodology for the routine quality control of this medicine, in situations where other methods are less accessible in the laboratory.     

HPLC determination of morphine with amperometric detection at low potentials under basic pH conditions

Summary A simple, sensitive, accurate and reliable method for morphine determination in biological samples has been developed. It uses reverse-phase HPLC on a polymeric column with an eluent (0.05 mol/L dibasic sodium phosphate: acetonitrile, 8515) at pH 9.5, allowing both the suppression of ionization of morphine amine and the promotion of oxidation of the phenolic group. Amperometric detection at mild oxidizing potential (350 mV) proves very selective, and, therefore, only a simple and rapid one-step liquid-liquid sample preparation is required. Under these conditions clean chromatograms are obtained even with complex biological matrices such as cadaveric blood, urine and hair.Minimum detectable amount of morphine is about 200 pg injected. A calibration line with a correlation coefficient of 0.99996 has been produced over the range 7.5–250 ng/mL. Precision results comparable to other HPLC methods.A preliminary report was presented at the 25th T.I.A.F.T. Meeting 1988, Groningen (NL), June 27–30 1988.     

Improved stability of Opalmon tablets under humid conditions IV: effect of polysaccharides and disintegrants on the stability and dissolution property of Opalmon tablets

We studied the effects of dextran, dextrin, and disintegrants on the chemical stability of Opalmon tablets containing Limaprost-alfadex (Limaprost/alpha-cyclodextrin complex) and found that the addition of dextran or dextrin significantly improved the chemical stability of Opalmon tablets under high humidity, compared to lactose. We also examined how dextran stabilizes Limaprost in Opalmon tablets and studied the formulation of Opalmon tablets in order to achieve higher chemical stability, rapid dissolution and reduced stickiness. The results suggested that dextran increases stabilization after moisture adsorption by decreasing the dissociation of Limaprost-alfadex to the free drug and alpha-cyclodextrin in the dextran matrix, when compared with the lactose matrix. The stickiness of Opalmon tablets containing dextran and dextrin was negligible when dextran and dextrin amounted to less than 20% of the formulation. By selecting a proper disintegrant, we obtained Opalmon tablets with higher chemical stability and rapid dissolution properties.     

On the mechanism of ferrocene oxidation under the conditions of electrospray ionization

Russian Chemical Bulletin - The formation of molecular ions of ferrocene is detected under the «inverse» conditions of electrospray ionization where the pure solvent alone is...     

Unraveling the crystallization mechanism of CoAPO-5 molecular sieves under hydrothermal conditions

The hydrothermal crystallization of CoAPO-5 molecular sieves has been studied using time-resolved in-situ SAXS/WAXS, UV-vis, Raman, and XAS. Data collected during heating to 180 degrees C allowed the observation of different steps occurring during the transformation of the amorphous gel into a crystalline material from a macroscopic and atomic perspective. Raman spectroscopy detected the initial formation of Al-O-P bonds, whereas SAXS showed that these gel particles had a broad size distribution ranging from ca. 7 to 20 nm before crystallization began. WAXS showed that this crystallization was sharp and occurred at around 160 degrees C. Analysis of the crystallization kinetics suggested a one-dimensional growth process. XAS showed that Co(2+) transformed via a two-stage process during heating involving (i) a gradual transformation of octahedral coordination into tetrahedral coordination before the appearance of Bragg peaks corresponding to AFI, suggesting progressive incorporation of Co(2+) into the poorly ordered Al-O-P network up to ca. 150 degrees C, and (ii) a rapid transformation of remaining octahedral Co(2+) at the onset of crystallization. Co(2+) was observed to retard crystallization of AFI but provided valuable information regarding the synthesis process by acting as an internal probe. A three-stage, one-dimensional crystallization mechanism is proposed: (i) an initial reaction between aluminum and phosphate units forming a primary amorphous phase, (ii) progressive condensation of linear Al-O-P chains forming a poorly ordered structure separated by template molecules up to ca. 155 degrees C, and (iii) rapid internal reorganization of the aluminophosphate network leading to crystallization of the AFI crystal structure.     

The molecular mechanism of low-temperature decomposition of hydrogen sulfide under conjugated chemisorption-catalysis conditions

The molecular mechanism of interaction of two hydrogen sulfide molecules with the (Co^III-H_o)₂S₂(SH₂)₄ model active center containing occluded hydrogen was studied by the density functional theory method with the B3P86 hybrid exchange-correlation functional. The reaction was found to occur in the following elementary steps: molecular adsorption of hydrogen sulfide ? dissociative chemisorption ? S-S bond formation in the surface intermediate {2Co^III ? (μ-S₂) + 2H(ads)} with the release of the first hydrogen molecule into the gas phase H₂(g) ? the release of the second hydrogen molecule into the gas phase H₂(g) ? the formation of cyclooctasulfur in the reaction 4S₂(ads) → S₈(ads). The first three steps occur spontaneously at room temperature, the thermodynamic driving force of the process being the stoichiometric reaction of S-S bond formation at the stage of conjugated chemisorption of two hydrogen sulfide molecules on two adjacent metal ions with the release of the first hydrogen molecule into the gas phase. The catalytic cycle is terminated by the recombination of molecular sulfur S₂ into cyclooctasulfur S₈ in the adsorption layer and the release of the second hydrogen molecule into the gas phase.     

Application of 28Mg for characterization of Mg uptake in rice seedling under different pH conditions

The magnesium (Mg) uptake of rice seedlings treated with different pH solutions was investigated using tracer of ²⁸Mg. The application of ²⁸Mg enabled the determination of Mg uptake amount within 15 min of the different pH treatments. The uptake amount of ²⁸Mg and its distribution in rice plants were determined by using the imaging plate. The result demonstrated that the Mg uptake amount was approximately 3 μmol/15 min per plant in 0.27 mM Mg solution at pH 5.6, and this uptake decreased by 30 % at lower pH conditions (pH 4.5). On the contrary, the pH 6.5 condition induced the Mg uptake activity to 4.4 μmol/15 min. The inverse relationship found between proton concentration in nutrient solution and the Mg uptake amount within 15 min of treatment demonstrated that the low pH condition could inhibit the Mg uptake activity as a consequence of the competition between Mg²⁺ and proton. It is concluded that under low pH conditions, regardless of other factors, there is a decrease of Mg uptake activity in rice roots.     

Optimum heat treatment conditions for masking the bitterness of the clarithromycin wax matrix

The effects of the contents of aminoalkyl methacrylate copolymer E (AMCE) in a wax matrix on the mechanism of polymorphic transformation of glyceryl monostearate (GM) were clarified by evaluating the enthalpy change defined as 1.51 (DeltaH(1)-DeltaH(2))/DeltaH(2), where DeltaH(1) and DeltaH(2) denote the enthalpies in the first and second thermal analyses, respectively. Using this value, K(1), the rate constant of transformation from alpha-form to beta'-form, and K(2), the rate constant of transformation from beta'-form to beta-form, could be obtained. As the ratio of AMCE increased, K(2) increased, but a minimum point existed for K(1). K(1) was always larger than K(2), but gradually approached K(2) as the ratio of AMCE increased. The optimum temperature for the transformation of GM was 50 degrees C, at which the enthalpy change was maximum. To prepare the wax matrix preparation of clarithromycin (CAM), we considered 40 degrees C the optimum treatment temperature for the transformation of GM in a CAM wax matrix compounded from CAM, GM and AMCE, since the matrices were mutually welded at above 45 degrees C during the spray congealing process. Although K(1) and K(2) were almost the same at 40 degrees C, the rate of transformation was accelerated by tumbling. By applying the tumbling that accelerated the transformation of GM in a CAM wax matrix, almost all of the alpha-form disappeared, and the release of CAM from the wax matrix diminished when the enthalpy change was more than 0.8.     

Electromembrane extraction of basic drugs from untreated human plasma and whole blood under physiological pH conditions

The present work describes the first systematic study of electromembrane extraction (EME) from biological matrices under physiological conditions. Six basic drugs with protein binding in the range of 20–97% were extracted from untreated human plasma and whole blood through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene impregnated in the walls of a hollow fiber, and into an acidified aqueous solution inside the lumen of the fiber. The electrical potential difference over the membrane reduced the protein binding of the drugs and transported the free drug fraction over the membrane. Recoveries in the range 25–65% were obtained with 10-min extraction time and an applied voltage of only 10 V over the SLM. Interday precision better than 20% RSD and linearity in the range 0.5–10 μg/mL were obtained for nortriptyline and methadone. Extraction from untreated whole blood was also demonstrated with recoveries in the range 19–51%.     

Kinetics and mechanism of protection of thymine from sulphate radical anion under anoxic conditions

The rates of photooxidation of thymine in presence of peroxydisulphate (PDS) have been determined by measuring the absorbance of thymine at 264 nm spectrophotometrically. The rates and the quantum yields (φ) of oxidation of thymine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in [caffeic acid] is found to decrease the rate of oxidation of thymine suggesting that caffeic acid acts as an efficient scavenger of SO ₄ ^•- and protects thymine from it. Sulphate radical anion competes for thymine as well as for caffeic acid. The rate constant of sulphate radical anion with caffeic acid has been calculated to be 1.24 x 10¹⁰ dm³ mol^-1s^-1. The quantum yields of photooxidation of thymine have been calculated from the rates of oxidation of thymine and the light intensity absorbed by PDS at 254 nm, the wavelength at which PDS is activated to sulphate radical anion. From the results of experimentally determined quantum yields (φ_expt1) and the quantum yields calculated (φ_cl) assuming caffeic acid acting only as a scavenger of SO ₄ ^•- radicals show that φ_expt1 values are lower than φ_cl values. The φ ’ values, which are experimentally found quantum yield values at each caffeic acid concentration and corrected for SO ₄ ^•- scavenging by caffeic acid, are also found to be greater than φ_expt1 values. These observations suggest that the thymine radicals are repaired by caffeic acid in addition to scavenging of sulphate radical anions.     

Atomic force microscopy investigation of the mechanism of calcite microcrystal growth under Kitano conditions

A combined atomic force microscopy (AFM)-inverted optical microscopy technique has been used to image the surface of calcite single microcrystals, with dimensions of 10-20 microm, at high resolution. The microcrystals were grown on a glass substrate using the Kitano method, a process that involves the outgassing of carbon dioxide from a saturated solution of calcium carbonate. The resulting increase in the supersaturation of the solution, with respect to calcium carbonate, induces crystallization. It is demonstrated, for the first time, that calcite microcrystals formed in this way exhibit a single spiral growth hillock on the (104) surface, as evidenced by a spiral step pattern, indicating that growth occurs at steps arising from an individual screw dislocation. The subsequent reactivity of these crystals under Kitano conditions has been followed in situ using AFM imaging.