Thermodynamics of Association of Structurally Related Amphiphilic Penicillins

Critical micelle concentrations (CMCs) of the penicillins cloxacillin and dicloxacillin in water were determined by conductivity measurements over the temperature range 288.15 to 313.15 K. Both penicillins showed minimum CMCs at temperatures close to 298.15 K. Thermodynamic parameters of aggregate formation were derived from the variation of the CMC with temperature using a modified form of the mass action model applicable to systems of low aggregation number. Values for the enthalpy of aggregate formation, DeltaH(0)(m), calculated by this method showed that the aggregation of both cloxacillin and dicloxacillin became increasingly exothermic with increase in temperature. The predicted DeltaH(0)(m) at 298.15 K was in good agreement with the value determined experimentally by calorimetry for each drug. Copyright 2000 Academic Press.     

A thermodynamic study of two anionic amphiphilic penicillins in aqueous solution by ultrasound speed measurements

The critical concentrations of sodium cloxacillin and sodium dicloxacillin penicillins in aqueous solution were determined over the temperature range 288.15–313.15 K by a method based on deconvolution into Gaussians of the second derivative of the measured ultrasound velocity. The mass action model was used to calculate the thermodynamic standard quantities: free Gibbs energy, enthalpy and entropy of aggregate formation. The results are discussed in terms of the structure of the drug aggregates.     

Factors influencing reverse osmosis rejection of inorganic solutes from aqueous solution

Reverse osmosis (RO) rejection is strongly influenced by the distribution of solute between the membrane and solvent phases. For this reason, we examined the partition coefficients of inorganic compounds between water and cellulose acetate (CA) membranes. Cation and anion partition coefficients were determined by independent analyses. Effects of fixed (negative) membrane charges on CA are clearly apparent at low solute concentrations. The mean cation/anion partition coefficients decrease with the product of the cation and anion valence, and increase with increasing ionic size. Un-ionized inorganic compounds, HgC1₂ and HAuC1₄, are strongly sorbed by CA membranes. All of these observations are consistent with electrostatic theory.Experimental membrane/water partition coefficients are influenced by temperature, pH, and ion-pairing. CA membranes exhibit swelling and shrinkage when exposed to certain aqueous solutions. Swelling and shrinkage influence solute partition and diffusion coefficients, the water content of the membranes, and their RO rejection.The present results provide a comprehensive experimental basis for understanding the mechanism of RO rejection by CA membranes. Moreover, these results can be used to predict RO behavior under a wide variety of experimental conditions. The potential use of reverse osmosis in a variety of wastewater applications is considered in some detail.     

Rapid assay for procaine penicillin G in pharmaceutical dosages by spectrofluorimetry

A method for the spectrofluorimetric determination of procaine penicillin G is proposed (lambda(ex) = 294 nm, lambda(em) = 348 nm) for concentrations between 0.10 and 1.0 ppm. The method was performed in ethanol/water medium (60% V/V), at apparent pH 9.9 provided by adding ammonium/ammonia buffer solution with pH = 10.0. The effect of other penicillins on the determination of procaine penicillin G was examined over a wide range of concentrations, interferences were not observed in the range of studied concentrations. The method was successfully applied to assay all Spanish commercialized injections containing procaine penicillin G, penicillin G and/or benzathine penicillin G.     

氨基酸-醇-水体系的密度与表观摩尔体积

用DMA602/60型震动管数字密度计测定了298.15 K下甘氨酸、丙氨酸分别在纯水和四个不同浓度甲醇、乙醇和丙醇水溶液中的密度, 计算了相应的表观摩尔体积, 用最小二乘法拟合了氨基酸在醇水溶液中的标准偏摩尔体积. 根据McMillan-Mayer理论拟合了水溶液中氨基酸分别与醇相互作用的对相互作用参数Vab和三相互作用参数Vabb, Vaab. 结果表明甘氨酸、丙氨酸在醇水溶液中的表观摩尔体积都随醇浓度的增加而增加, 都属亲水破坏性溶质; 其自相互作用参数和三相互作用参数均为正值, 对相互作用参数Vab均为负值且随烃基链的延长, 负值依次增大. 分别根据极性分子的相互作用模型、结构水化模型和溶剂分离缔合模型进行了讨论.     

Excess free energy,enthalpy and entropy of surfactant-surfactant mixed micelle formation

Enthalpies of dilution and osmotic coefficients of sodium decylsulfate (NaDeS)-dodecyldimethylamine oxide (DDAO) mixtures in water were determined at 298 and 310 K, respectively. From the enthalpies of dilution, the apparent and then the partial molar relative enthalpies of the surfactant mixtures were calculated. From the osmotic coefficients, calculated at 298 K, the non-ideal free energies were derived. The latter were combined with the partial molar relative enthalpies to obtain the non-ideal entropies. From the apparent molar properties, using a previously reported approach, the excess thermodynamic properties for the surfactant-surfactant mixed micelle formation in water were evaluated as functions of the mixture composition at some total micellized concentration. In the whole range of the mixture composition, the excess free energy is negative, indicating that the mixed micelle formation is favoured with respect to that of pure micelles. This process is governed by the enthalpy and/or the entropy, depending on the mixture composition. The effect of the alkyl chain length was also studied by comparing the present results to those of the sodium dodecylsulfate-DDAO mixture.     

水+甲烷系统的气液相边界曲线和临界曲线

采用带有蓝宝石视窗和磁力搅拌的可变体积高压斧得出了水+甲烷系统的气液相边界曲线和临界曲线. 实验温度为433.0-633.0 K, 实验压力为30.00-300.00 MPa. 实验确定了甲烷在富水区的亨利系数, 结果显示, 在433.0-603.0 K的温度范围内, 此亨利系数随着温度的升高而下降. 本文还研究了甲烷+水系统的气液分配比以及偏摩尔溶解焓和偏摩尔溶解熵数据. 结果发现, 甲烷和水的内聚能密度差别很大.     

Study of Interactions Between Sugammadex and Penicillins Using Affinity Capillary Electrophoresis

Sugammadex, a new modified gamma cyclodextrin, reverses the neuromuscular blockage induced by rocuronium by forming a strong complex with this muscle relaxant. To evaluate possible interactions with potentially co-administered drugs, interactions between sugammadex and penicillins were investigated using the affinity capillary electrophoresis method for the first time. Capillary electrophoresis coupled to an ultra violet detector was used as an analytical device for the analysis and detection of cyclodextrin inclusion complexes. Changes in the effective mobility of guest drugs (amoxicillin, ampicillin, oxacillin, dicloxacillin and azlocillin) were correlated with the increasing concentration of host molecules in background electrolyte, and successfully fitted into a non-linear curve equation; assuming 1:1 stoichiometric interaction. The calculated association constants (K _a) were: 383.44, 184.54, 265.34 and 95.06 M^?1 for amoxicillin, ampicillin, oxacillin and dicloxacillin, respectively. No complex formation with sugammadex could be detected for both penicillin G and piperacillin. The difference in the chemical structure of the penicillins, especially in the (R) side chains, is suggested to be responsible for the variety of binding strength between penicillins and sugammadex. The displacement study demonstrated that interactions between sugammadex and co-administered penicillins could reduce the pharmacological effects of both.     

Study of Interactions Between Sugammadex and Penicillins Using Affinity Capillary Electrophoresis

Sugammadex, a new modified gamma cyclodextrin, reverses the neuromuscular blockage induced by rocuronium by forming a strong complex with this muscle relaxant. To evaluate possible interactions with potentially co-administered drugs, interactions between sugammadex and penicillins were investigated using the affinity capillary electrophoresis method for the first time. Capillary electrophoresis coupled to an ultra violet detector was used as an analytical device for the analysis and detection of cyclodextrin inclusion complexes. Changes in the effective mobility of guest drugs (amoxicillin, ampicillin, oxacillin, dicloxacillin and azlocillin) were correlated with the increasing concentration of host molecules in background electrolyte, and successfully fitted into a non-linear curve equation; assuming 1:1 stoichiometric interaction. The calculated association constants (K _a) were: 383.44, 184.54, 265.34 and 95.06 M⁻¹ for amoxicillin, ampicillin, oxacillin and dicloxacillin, respectively. No complex formation with sugammadex could be detected for both penicillin G and piperacillin. The difference in the chemical structure of the penicillins, especially in the (R) side chains, is suggested to be responsible for the variety of binding strength between penicillins and sugammadex. The displacement study demonstrated that interactions between sugammadex and co-administered penicillins could reduce the pharmacological effects of both.

     

甘氨酸在尿素、甲脲及二甲脲水溶液中的体积性质

用精密数字密度计测定了甘氨酸在不同质量分数的尿素、甲脲和二甲脲水溶液中的密度,计算了甘氨酸的极限偏摩尔体积、迁移偏摩尔体积、理论水化数和体积作用系数,讨论了溶剂组成变化对甘氨酸迁移偏摩尔体积和理论水化数的影响.结果表明,甘氨酸与尿素及烷脲分子间的相互作用主要以1:1的形式为主.尿素、甲脲、二甲脲分子与氨基酸荷电中心的直接相互作用,削弱了两性离子带电中心对周围水分子的电致收缩效应,造成了理论水化数随溶液浓度的增加而减小.     

Prediction of partition coefficients in ternary liquid-liquid systems as a function of the phase system composition by factor analysis for

The measured partition data of 26 steroids for six different compositions of ternary liquid-liquid systems consisting of 2,2,4-trimethylpentane, ethanol and water are used in calculations of partition data for new phase system compositions. It was possible to reproduce the original data and to verify new experimental data by this calculation with high accuracy. Calculations were done in three ways. In the first, non-linear regression of the partition coefficients as a function of the phase system composition was examined. With this classical approach it is possible to calculate the values of the partition coefficients, solute by solute, with good accuracy. In the second approach, principal component factor analysis was used. The phase system-specific factors for further phase system compositions were calculated with a non-linear regression of these factors on the phase system composition. In combination with the solute-specific factors, the values of the partition coefficients for all solutes in any phase system composition could be predicted with excellent accuracy. In the third approach, target transformation factor analysis was applied. A relationship between the partition coefficient and the phase system composition was established on the basis of either the phase system composition itself or a simple function of it. This method also gave very accurate predictions of known and unknown partition coefficients.     

Solubilization of dodac small unilamellar vesicles by sucrose esters: A fluorescence study

A fluorescence method was employed to study the solubilizing interactions of several sucrose esters with Dioctadecyldimethylammonium chloride small unilamellar vesicles. In this paper we studied four different alkyl esters of sucrose, saturation and solubilization concentrations (C_sat and C_sol), the ester–DODAC molar ratio (R_e) and bilayer/aqueous partition coefficients (K) were measured by monitoring changes in laurdan generalized polarization values. A new critical surfactant concentration at lower values than saturation concentration was observed. All critical concentrations showed linear dependence with DODAC concentration. The decrease in the length of surfactant alkyl chain (upper cmc) led to an increase in its ability to saturate and solubilize vesicles and to a decrease in its bilayer affinity. Consequently the shorter alkyl chain (lauryl sucrose ester), the higher ability to saturate and solubilize the vesicles, whereas the longer chain (stearyl sucrose ester), exhibited the highest degree of partitioning into the vesicles.     

Effect of temperature on the density and surface tension of aqueous solutions of HMT

In this study, a systematic study of the effect of the temperature on the density and surface tension of HMT (hexamethylentetramine) in water was developed. The density and surface tension were determined at temperatures of 288.15, 293.15, 298.15, 303.15, and 308.15 K. Precise data of surface tension have not been reported previously in literature. From the density measurements, the apparent molar and partial molar volumes were calculated. The apparent molar volume decreases with concentration, the molar partial volume increases with temperature. The surface tension of the aqueous solutions of HMT decreases with concentration. The excess surface concentration was calculated, the values increase with concentration, indicating that the amount of HMT that goes to the interface gas liquid increases at higher concentrations of HMT.     

Diffusion coefficient and capacity factor in capillary electrokinetic chromatography with replaceable charged polymeric pseudophase

Apparent diffusion coefficients, Dapp,i, were determined in solutions with a polycationic additive -- poly(diallyidimethylammonium) -- acting as a pseudostationary phase for electrokinetic chromatography. They were determined for six small neutral analytes at five concentrations of the polymeric additive (between 0 and 4% w/w) by a stopped migration method. The apparent diffusion coefficients decrease with increasing polymer concentration only within 40% maximum, an effect that cannot be associated with the macroscopic viscosity of the polymer solution (which increases by a factor of 10). The change of the apparent diffusion coefficients is related to the interaction of the neutral analyte molecules with the polyelectrolyte chain. Applying the model of analyte partitioning between "free" solution and polymer, capacity factors and partition constants were derived from the slope of the 1/Dapp,i vs. polymer concentration curves. Partition constants determined by this method (ranging between 40 and 170) agree with those obtained by electrokinetic chromatography.     

Apparent Molar Volume and Apparent Molar Expansibility of Rubidium, Cesium, and Ammonium Cyclohexylsulfamate in Aqueous Solution

Summary. The apparent molar volume of rubidium, caesium, and ammonium cyclohexylsulfamate was determined from the density data of their aqueous solutions at 293.15, 298.15, 303.15, 313.15, 323.15, and 333.15 K. From the apparent molar volume, determined at various temperatures, the apparent molar expansibility was calculated. The limiting apparent molar volume and apparent molar expansibility were evaluated and apportioned into their ionic components. The limiting partial molar ionic volumes and expansibilities are discussed in terms of the various effects of the ion in solution on the structure of water. It was shown that the limiting partial molar ionic expansibilities of the alkali-metal cations increase with their ionic radii. The coefficients of thermal expansion of the investigated solutions at 298.15 K were calculated and are presented graphically together with some alkali-metal cyclohexylsulfamates and tetramethylammonium cyclohexylsulfamate. The densities of the investigated solutions can be adequately represented by an equation derived by Redlich.     

Apparent Molar Volume and Apparent Molar Expansibility of Rubidium, Cesium, and Ammonium Cyclohexylsulfamate in Aqueous Solution

The apparent molar volume of rubidium, caesium, and ammonium cyclohexylsulfamate was determined from the density data of their aqueous solutions at 293.15, 298.15, 303.15, 313.15, 323.15, and 333.15 K. From the apparent molar volume, determined at various temperatures, the apparent molar expansibility was calculated. The limiting apparent molar volume and apparent molar expansibility were evaluated and apportioned into their ionic components. The limiting partial molar ionic volumes and expansibilities are discussed in terms of the various effects of the ion in solution on the structure of water. It was shown that the limiting partial molar ionic expansibilities of the alkali-metal cations increase with their ionic radii. The coefficients of thermal expansion of the investigated solutions at 298.15 K were calculated and are presented graphically together with some alkali-metal cyclohexylsulfamates and tetramethylammonium cyclohexylsulfamate. The densities of the investigated solutions can be adequately represented by an equation derived by Redlich.     

Confirmatory determination of six penicillins in honey by liquid chromatography/electrospray ionization-tandem mass spectrometry

A confirmatory method for 6 penicillin antibiotics (amoxicillin, ampicillin, penicillin G, oxacillin, cloxacillin, and dicloxacillin) in honey is presented that allows determination and confirmation of identity of the antibiotics at trace levels. The method includes the use of a stable isotope-labeled internal standard benzyl (d7-phenyl) penicillate and removal of sugar and other substances by solvent and solid-phase extraction. The honey extracts are then analyzed for penicillin residues by liquid chromatography/electrospray ionization-tandem mass spectrometry. Mass spectral acquisition was achieved in an electrospray positive ion mode by applying multiple reaction monitoring of 2 or 3 fragment ion transitions to provide a high degree of sensitivity and specificity. Typical recoveries of 6 penicillins at fortification levels of 6, 16, 40, and 80 microg/kg ranged from 51.4 to 132.9%. The recoveries varied with the individual penicillins and were affected by different honey matrixes. The ion ratios were consistent and could be used for confirmation of identity of the penicillins. The method limits of detection (microg/kg) were 0.25 for amoxicillin, 0.19 for ampicillin, 0.068 for penicillin G, 0.028 for oxacillin, 0.052 for cloxacillin, and 0.085 for dicloxacillin. The method limits of confirmation (microg/kg) were 0.44 for amoxicillin, 0.52 for ampicillin, 0.23 for penicillin G, 0.14 for oxacillin, 0.14 for cloxacillin, and 0.15 for dicloxacillin when a sample size of 5 g honey was used.