pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode

Solute diffusion coefficients (D) can indicate a dependence upon actual solute concentrations. Here a single compartment has been utilized, in which effective HCl diffusion to a membrane-mounted glass pH electrode can be measured across the pH spectrum. The study has investigated HCl diffusion through both mucus and water layers as a function of HCl concentration. The observed dynamic responses of a liquid-film and mucus-coated electrodes over a range of HCl concentrations suggest that the speed at which equilibrium is attained is pH dependent; equilibrium was reached rapidly under more acidic and alkaline conditions. Estimated values of DHCl also indicate a strong pH dependence for both liquid film and mucus. In both instances, a greater than 10-fold reduction in DHCl at pH 7.5 as compared with that at pH 3.5 has been demonstrated. Furthermore, estimated values of DHCl are approximately 4-fold smaller through the mucus gel, as compared with a water layer. The findings indicate that the most powerful influence on diffusional resistance is pH itself, whereby a marked drop in H+ diffusion is likely to occur towards neutral pH irrespective of the composition of the gel barrier. Possible implications of the findings are discussed in relation to mucosal protection from acid.     

Effects of simple model solutes on water dynamics: residence time analysis

The water residence time around pairs of simple hydrophilic and hydrophobic solutes, kept immobilized to model groups on slowly diffusing macromolecules, has been investigated along 400 ps molecular dynamics simulations. Results show that the water mobility around one solute strongly depends on the polarity characteristics of the other solute of the pair.     

A spray technique for the determination of membrane diffusion and distribution coefficients by the time-lag method: evaluated for electrolyte transport through charged and uncharged membranes

Using solution sprays, a sharp concentration step may be effected at the surface of a membrane in less than 0.1 sec. This technique allows the time-lag method to be used to determine rapidly both solute permeability and diffusion coefficient in a single experiment. From the mathematical analysis of diffusion into a cell with finite collecting volume, limiting conditions are derived which define experimental conditions under which the conventional linear, steady state analysis of time lag will be valid. These limiting conditions were used to determine the dimensions of the experimental diffusion cell. Diffusion, permeability and distribution coefficients were measured for a variety of electrolytes in both charged and uncharged membranes and shown to be in good agreement with conventional methods. A Donnan analysis is given by which the charged nature of an unknown membrane may be assessed precisely and rapidly.     

Kinetic spectrophotometric method for determination of perphenazine based on monitoring the oxidation intermediate by applying a stopped-flow technique

A novel and high-sensitive stopped-flow kinetic spectrophotometic method for the determination of perphenazine based on monitoring the variation of absorbance of the intermediate within a few seconds has been developed. The optimum conditions for various parameters on which the forming of the intermediate depends, were investigated. It was found that the initial reaction rate increased linearly with an increase in the perphenazine concentration in the range from 1.0 x 10(-5) to 1.6 x 10(-4)M. The detection limit was calculated to be 5.3 x 10(-6)M. The kinetics of the reaction was established by the aid of single-mixing or double-mixing stopped-flow techniques, a successive reaction model was proposed to analyze and simulate the reaction. The influence of both ascorbic acid and NADH on the time courses was also investigated.     

Estimation of physical properties of transition metals based on a configuration model of solids

A new empirical formula for estimation of the entropyS°₂₉₈ of transition metals is suggested. On the basis of this formula some equations that enable calculation of other physical properties, for example density and molar heat capacity, have been derived.Dedicated to Prof. Dr.Kurt L. Komarek on the occasion of his 60th birthday.     

Characterization of ultrafiltration membranes. : Part IV. Influence of the deformation of macromolecular solutes on the transport through ultrafiltration membranes.

A theory was developed to point out the important parameters involved in the deformation of a flexible polymer in ultrafiltration through membranes. It appears that the deformation, and thus the easier transport of the polymer solute, occurs when the permeate flux reaches (or exceeds) a critical value which depends on the solution characteristics (solvent viscosity, concentration, temperature) as well as the membrane surface characteristics (porosity and pore radius on the surface). The experimental study was carried out with two flexible polymers: polyethylene glycol (PEG) and dextran. In ultrafiltration under constant pressure through a IRIS 3042 membrane, the increase of the concentration of PEG (of molecular weights 15,000, 20,000, 35,000) beyond a certain value caused a steady drop of rejection from a constant value. On the other hand, the increase of the applied pressure in the ultrafiltration of PEG 35,000 and dextran 70,000 afforded a sharp drop of rejections to a zero value as the fluxes increased steadily. Conversely, the changes in the concentration or the applied pressure did not affect the rejection when membranes of low permeability (Nuclepore 150 A, IRIS 3069) or of low pore size (PTGC) were used. These behaviours are consistent with the established theory.     

Estimation of molecular similarity based on 4D-QSAR analysis: formalism and validation

The 4D-QSAR paradigm has been used to develop a formalism to estimate molecular similarity measures as a function of conformation, alignment, and atom type. It is possible to estimate the molecular similarity of pairs of molecules based upon the entire ensemble of conformational states each molecule can adopt at a given temperature, normally room temperature. Molecular similarity can be measured in terms of the types of atoms composing each molecule leading to multiple measures of molecular similarity. Multiple measures of molecular similarity can also arise from using different alignment rules to perform relative molecular similarity, RMS, analysis. An alignment independent method of determining molecular similarity measures, referred to as absolute molecular similarity, AMS, analysis has been developed. Various sets and libraries of compounds, including the amino acids, are analyzed using 4D-QSAR molecular similarity analysis to demonstrate the features of the formalism. Exploration of molecular similarity as a function of chirality, identification of common embedded 3D pharmacophores in compounds, and elucidation of 3D-isosteric compounds from structurally diverse libraries are carried out in the application studies.     

Plum-pudding gels as a platform for drug delivery: understanding the effects of the different components on the diffusion behavior of solutes

The internal structure of composite gels made of responsive microgel particles inserted into a bulk hydrogel (N-isopropylacrylamide microgel particles in a cross-linked dimethylacrylamide matrix) has been investigated from the diffusion behavior of poly(ethylene glycol) (PEG) probes through the network, in the absence of specific interactions between the diffusing molecules and the system. The effect of the different components has been examined, for example, the size of the probe, the bulk structure, and the microgel nature. Particles were characterized prior to their insertion into the hydrogel in order to describe their properties as a function of size and cross-linker content, thus revealing different swelling behaviors. The biggest effects on the diffusion of the PEG probes were related to the bulk structure, and no major effects were registered by the addition of different microgels into the hydrogel network. We attempt to rationalize this behavior in terms of the composite gel structure and discuss the results in terms of their meaning for controlled drug delivery strategies.     

Heat capacity effects associated with the hydrophobic hydration and interaction of simple solutes: a detailed structural and energetical analysis based on molecular dynamics simulations

We examine the SPCE [H. J. C. Berendsen et al., J. Chem. Phys. 91, 6269 (1987)] and TIP5P [M. W. Mahoney and W. L. Jorgensen, J. Chem. Phys 112, 8910 (2000)] water models using a temperature series of molecular-dynamics simulations in order to study heat-capacity effects associated with the hydrophobic hydration and interaction of xenon particles. The temperature interval between 275 and 375 K along the 0.1-MPa isobar is studied. For all investigated models and state points we calculate the excess chemical potential for xenon employing the Widom particle insertion technique. The solvation enthalpy and excess heat capacity is obtained from the temperature dependence of the chemical potentials and, alternatively, directly by Ewald summation, as well as a reaction field based method. All three methods provide consistent results. In addition, the reaction field technique allows a separation of the solvation enthalpy into solute/solvent and solvent/solvent parts. We find that the solvent/solvent contribution to the excess heat capacity is dominating, being about one order of magnitude larger than the solute/solvent part. This observation is attributed to the enlarged heat capacity of the water molecules in the hydration shell. A detailed spatial analysis of the heat capacity of the water molecules around a pair of xenon particles at different separations reveals that even more enhanced heat capacity of the water located in the bisector plane between two adjacent xenon atoms is responsible for the maximum of the heat capacity found for the desolvation barrier distance, recently reported by Shimizu and Chan [J. Am. Chem. Soc. 123, 2083 (2001)]. The about 60% enlarged heat capacity of water in the concave part of the joint xenon-xenon hydration shell is the result of a counterplay of strengthened hydrogen bonds and an enhanced breaking of hydrogen bonds with increasing temperature. Differences between the two models with respect to the heat capacity in the xenon-xenon contact state are attributed to the different water model bulk heat capacities, and to the different spatial extension of the structure effect introduced by the hydrophobic particles. Similarities between the different states of water in the joint xenon-xenon hydration shell and the properties of stretched water are discussed.     

Introducing a novel model for predicting effective thermal conductivity of spacer fabrics based on their structural parameters

Journal of Thermal Analysis and Calorimetry - The knowledge of the thermal properties of textiles is important with regard to their vast applications in most industries. Thermal properties, as one...     

High-performance thin-layer chromatography chemical fingerprinting: a modern technique for comparative assessment of a multivariate chromatogram analysis of Padina boergesenii

JPC – Journal of Planar Chromatography – Modern TLC - Gujarat’s coastline holds immense storage of valuable marine macroalgae. Padina boergesenii is normally familiar as leafy...     

Potential of mean force between a large solute and a biomolecular complex: a model analysis on protein flux through chaperonin system

Insertion of a large solute into an even larger vessel comprising biopolymers followed by release of the same solute from it is one of the important functions sustaining life. As a typical example, an unfolded protein is inserted into a chaperonin from bulk aqueous solution, a cochaperonin acting as a lid is attached to the chaperonin rim and the protein folds into its native structure within the closed cavity, the cochaperonin is detached after the folding is finished, and the folded protein is released back to the bulk solution. On the basis of the experimental observations manifesting that the basic aspects of the protein flux through the chaperonin system is independent of the chaperonin, cochaperonin, and protein species, we adopt a simple model system with which we can cover the whole cycle of the protein flux. We calculate the spatial distribution of the solvent-mediated potential of mean force (PMF) between a spherical solute and a cylindrical vessel or vessel/lid complex. The calculation is performed using the three-dimensional integral equation theory, and the PMF is decomposed into energetic and entropic components. We argue that an unfolded protein with a larger excluded volume (EV) and weak hydrophobicity is entropically inserted into the chaperonin cavity and constrained within a small space almost in its center. The switch from insertion to release is achieved by decreasing the EV and turning the protein surface hydrophilic in the folding process. For this release, in which the energetic component is a requisite, the feature that the chaperonin inner surface in the absence of the cochaperonin is not hydrophilic plays essential roles. On the other hand, the inner surface of the chaperonin/cochaperonin complex is hydrophilic, and the protein is energetically repelled from it: The protein remains constrained within the small space mentioned above without contacting the inner surface for correct folding. The structural and inner-surface properties of the chaperonin or complex are controlled by the adenosine triphosphate (ATP) binding to the chaperonin, hydrolysis of ATP into adenosine diphosphate (ADP) and Pi, and dissociation of ADP and Pi. The function of the chaperonin system is exhibited by synchronizing the chemical cycle of ATP hydrolysis with hydration properties of a protein in the water confined on the scale of a nanometer which are substantially different from those in the bulk water.     

Development of a univariate calibration model for pharmaceutical analysis based on NIR spectra

Near-infrared spectroscopy (NIRS) has been widely used in the pharmaceutical field because of its ability to provide quality information about drugs in near-real time. In practice, however, the NIRS technique requires construction of multivariate models in order to correct collinearity and the typically poor selectivity of NIR spectra. In this work, a new methodology for constructing simple NIR calibration models has been developed, based on the spectrum for the target analyte (usually the active principle ingredient, API), which is compared with that of the sample in order to calculate a correlation coefficient. To this end, calibration samples are prepared spanning an adequate concentration range for the API and their spectra are recorded. The model thus obtained by relating the correlation coefficient to the sample concentration is subjected to least-squares regression. The API concentration in validation samples is predicted by interpolating their correlation coefficients in the straight calibration line previously obtained. The proposed method affords quantitation of API in pharmaceuticals undergoing physical changes during their production process (e.g. granulates, and coated and non-coated tablets). The results obtained with the proposed methodology, based on correlation coefficients, were compared with the predictions of PLS1 calibration models, with which a different model is required for each type of sample. Error values lower than 1-2% were obtained in the analysis of three types of sample using the same model; these errors are similar to those obtained by applying three PLS models for granules, and non-coated and coated samples. Based on the outcome, our methodology is a straightforward choice for constructing calibration models affording expeditious prediction of new samples with varying physical properties. This makes it an effective alternative to multivariate calibration, which requires use of a different model for each type of sample, depending on its physical presentation.     

Prediction of infinite dilution activity coefficients for systems including water based on the group contribution model with mixture-type groups: II. Extension and application

Group contribution models such as ASOG or UNIFAC were known to be inaccurate in the prediction of infinite dilution activity coefficients (γ^∞) for most of the systems containing water. To overcome the weakness inherent with the UNIFAC models, Zhang et al. (Fluid Phase Equil. 149 (1998) 27) have recently proposed a group-contribution-based model with mixture-type groups, where the mixture-type group is a hypothetical concept for taking into account the particular hydrophobic effects in aqueous organic systems. The proposed methodology has been proven to be applicable to alkane/water and alcohol/water mixtures in our previous study. In this work, the proposed method was further extended to the other classes of compounds, e.g. aromatics, ketones, acids, aldehydes, esters, ethers, nitriles and halogenated compounds. Compared to the conventional UNIFAC models, the proposed method demonstrates significant improvements in accuracy for various organic compounds in water mixtures.     

Determination of loratadine and pseudoephedrine sulfate in pharmaceuticals based on non-linear second-order spectrophotometric data generated by a pH-gradient flow injection technique and artificial neural networks

Loratadine (LOR) and pseudoephedrine sulfate (PES) were determined in pharmaceutical samples by using non-linear second-order data generated by a pH-gradient flow injection analysis (FIA) system with diode-array detection. Determination of both analytes was performed on the basis of differences between the acid–base and spectral features of each drug species. Non-linearities were detected by using both qualitative and quantitative tools. As a consequence of the non-linearity, a recently reported algorithm, artificial neural networks followed by residual bilinearization (ANN/RBL), was shown to furnish more satisfactory results. Recoveries of 99.7% (LOR) and 95.6% (PES) were obtained when analyzing a validation set containing unexpected components (the usual excipients found in pharmaceutical preparations). The average value obtained by implementation of the method on four replicates was compared with that obtained by a reference method based on HPLC (difference not significant; p > 0.05).     

A model of cooperativity based on restricted binding: kinetic and thermodynamic analysis

Cooperative protein–ligand binding is an essential biochemical process. In this work, we introduce a model that can simulate the emergence of such phenomenon in the binding kinetics. It is based on the inability of the ligand molecules to fully utilize all the available binding sites due to some restriction, realized here in terms of a model parameter, called the restriction parameter. The theory is developed at the level of a single oligomeric protein molecule interacting with a ligand, maintained at a constant concentration, using a chemical master equation. The model provides stepwise binding constants related to the restriction parameter. The relative magnitudes of these constants, when compared to the Hill coefficients measuring cooperativity, give a physical insight in the development of the cooperative behavior and can also act as a reference frame. This can be useful for an alternative theoretical characterization of cooperativity in oligomeric proteins with large number of binding sites and arbitrary binding constants. We establish this point here by taking a tetrameric protein as a case study. A stochastic thermodynamic analysis is also performed, highlighting the energy–entropy contribution to the overall free energy change due to protein–ligand interaction for various cases of restricted binding.     

The application of thiosalts in analysis : Estimations based on decomposition of thiosalts Part C. Estimation of gold,platinum and antimony

The general method of forming and then decomposing the thiosalts has been applied to the gravimetric estimation of gold, platinum and antimony. In the case of gold and antimony the metals are weighed as Au₂S₃ and Sb₂S₃ respectively, while in the case of platinum, the precipitate of platinum sulphide is ignited and weighed as metal.     

The application of thiosalts in analysis : Estimations based on decomposition of thiosalts Part A. Estimation of arsenic,selenium and tellurium

1. It has been shown that the complete precipitation of arsenic sulphide (from arsenates) by decomposing the thiosalt provides a, lemarkably convenient and rapid method for its estimation which is in marked contrast to the tedious methods so far available for this purpose. 2. The method of precipitating the sulphide bv decomposing the thiosalt is also applicable to the estimation of tellurium for which no perfectly iclicibic gravimetric method had so far been devised. 3. Selenium also can be estimated gi avimetrically by this method and it provides a convenient alternative to the well-known method based upon I eduction to the metal. 4. The precipitates obtained in the case of arscnic, tellurium, and selenium correspond to the formulae As₂S₅, TeS₂ and SeS₂, respectively.