Differences In Partition Coefficients Research Articles

A Review on Method Development, Validation, Optimization and Applications of HPLC

Abstract: High-Performance Liquid Chromatography (HPLC) is a technique used to separate components from the mixture. The technology consists of two phases, the stationary phase, and the mobile phase. Component separation is based on differences in partition coefficients in two phases. The present review article focuses on the principle, types, instrumentation, process validation, application, advantages, disadvantages of HPLC. HPLC methods development and validation play important roles in the discovery, development, manufacture of pharmaceutical drugs, and various other studies related to humans and animals. An analytical procedure is developed to test a defining characteristic of the drug substance or drug product against established acceptance criteria for that characteristic. Validation of HPLC method as per ICH Guidelines covers all the performance characteristics of validation, like Accuracy, precision, specificity, linearity, range, the limit of detection, the limit of quantification, robustness, and system suitability testing. Keywords: HPLC, Types, Method validation, Method development, Instrumentation, and Applications.

Review on Methods and Applications of High-Performance Liquid Chromatography

High-Performance Liquid Chromatography is a technique used to separate components from the mixture. The technology consists of two phases, the stationary phase and the mobile phase. Component separation is based on differences in partition coefficients in two phases. HPLC is a form of liquid chromatography used to separate compounds dissolved in solution and qualitative and quantitative techniques used to evaluate pharmaceutical and biological samples. HPLC is the most widely used analytical separation technique for at quality control of pharmaceuticals. This mini-reviews include many aspects of HPLC, including type, instruments, and applications.

Practical aspects of the automated preparation of aqueous two phase systems for the analysis of biological macromolecules.

A robust strategy for the automated preparation of aqueous two-phase systems (ATPS) using a liquid handling sample processor was developed using gravimetric methods: to determine the accuracy of preparation. The major robotic control parameters requiring adjustment were; speed of aspiration and dispense; delay times following aspiration and dispense alongside measures to control cross-contamination during phase sampling. In general mixture compositions of both polymer/polymer and polymer/salt mixtures could be prepared with a target bias accuracy of less than 5%. However, we found that the bias accuracy with which systems of defined TLL and MR could be constructed was highly dependent on the tie line length of the ATPS and the geometrical form of the ATPS co-existence curve. For systems with a very low degree of curvature (PEG/salt systems here) increases in bias (accuracy) are appreciable at relatively long tie line lengths. Where the degree of curvature is more pronounced (PEG/dextran systems) closer approach to the critical point was possible without major effect on bias/accuracy. Application of the strategy to the measurement of the partitioning of phosphorylated and dephosphorylated forms of the model protein ovalbumin are reported. Differences in partition of phosphorylated (native) forms and dephosphorylated forms could be demonstrated. In a PEG/salt system this was manifest as a substantial decrease in solubility based on overall protein recovery derived from accurate knowledge of the system mass ratio. In a PEG/dextran system differences in partition coefficient could be demonstrated between phosphorylated and dephosphorylated forms.

An investigation of the efficacy and mechanism of contrast-enhanced X-ray computed tomography utilizing iodine for large specimens through experimental and simulation approaches.

BackgroundIodine-based solutions have long been known to be effective in aiding the differentiation among soft tissues in both fundamental anatomical research and for clinical diagnoses. Recently the combination of this particular contrasting agent with micro-computed tomography (micro-CT) has resulted in an array of high-quality image data, in which anatomical structures not visible in conventional CT can be identified and quantified. However, there has been only limited data available to inform detailed protocols for staining large specimens. Further, modeling of the staining mechanism has focused on simple diffusion processes.ResultsA low concentration of iodine-based buffered formalin solution with a long staining period was used to visualize soft-tissue structures in a large goose head. The staining effect was analyzed by serially measuring the micro-CT profiles across coronal sections throughout the staining period. Regular replacement of the staining solution combined with a longer staining period significantly improved contrast within tissues. A simplified one-dimensional Diffusion-Sorption model with a three-zone domain was used to simulate the diffusion process by calculating the concentration profile of iodine across the adductor region, which fits well with the experiment data. Observations of changes in the concentration of the staining agent and simulation results suggest that the sorption of iodine by tissues significantly affects the effective diffusion coefficient for the contrasting agent.ConclusionsThe Diffusion-Sorption model better explains previously reported difficulties in staining large samples comprised of tissues with high partition coefficients (Kd). Differences in partition coefficient (Kd), bulk density (ρb), and porosity (θ) could further explain the observed variation in staining rate and maximal staining effect among different tissues. Recommended protocols for staining large specimens are detailed.

Enhanced skin permeation of 6-methoxy-2-naphthylacetic acid by salt formation

The aim of this work was to prepare salts of 6-methoxy-2-naphthylacetic acid (6-MNA) to improve its physicochemical properties for percutaneous application. 6-MNA, an active metabolite of non-steroidal anti-inflammatory drug nabumetone has long half life and has the tendency to penetrate well into synovial fluid. The physicochemical properties of 6-MNA salts were investigated by solubility measurements, differential scanning calorimetry (DSC) and infrared (IR). The DSC thermograms and Fourier transform infrared (FT-IR) spectra indicated that 6-MNA formed salts with organic and alkali metal bases. Among the series, salts formed with amine bases (ethanolamine, diethanolamine, triethanolamine and diethylamine) had lower melting points while alkali metal salt (sodium) had higher melting point than 6-MNA. The salts had higher solubilities than 6-MNA as determined in phosphate buffer at pH 5.0 and 7.4. There is no significant difference in partition coefficient (log P) values between salts and 6-MNA at pH 5.0 but, at pH 7.4, the log P values for the salts increased by 4–10 times as compared to 6-MNA. In vitro permeation studies showed that all the salts increased the flux in comparision to 6-MNA, and the ethanolamine salt (1b) was found to be having 7.7 and 9.4 times higher permeability as compared to 6-MNA at pH 5.0 and 7.4, respectively.

Association of increased extracellular volume expansion with elevated left ventricular end diastolic pressure in patients with nonischemic cardiomyopathy

Background Myocardial extracellular volume expansion is a marker of myocardial fibrosis which is associated with myocardial stiffness and impaired relaxation property. In this study we investigated the association of extracellular volume indices using T1 mapping and left ventricular end diastolic pressure (LVEDP) using left atrial transit time in patients with nonischemic cardiomyopathy. Methods All subjects were prospectively recruited to undergo cardiac MRI in a 1.5 T scanner. Modified Look-Locker Inversion recovery sequence was used with motion correction included in the post processing algorithm. Pre-contrast and post contrast (20 minutes after gadolinium injection at 0.15 mmol/kg) T1 maps of the blood pool and myocardium were assessed in basal, mid and apical segments of the short axis planes using Siemens software. Calculated T1 indices were the average value of the basal and mid slice which included the pre- and post-contrast myocardial T1, contrast partition coefficient using the ratio of signal change in blood and myocardium before and after contrast administration, and extracellular volume fraction (ECV) which was partition coefficient multiplied with one minus hematocrit to account for the blood contrast volume of distribution. LVEDP was assessed using normalized mean left atrial transit time derived from the time-signal intensity curve of the first pass perfusion image during gadolinium injection at 0.01 mmol/kg. Results Compared to the normal controls (N = 8) patients with nonischemic cardiomyopathy (N = 31) had lower LV ejection fraction (EF) (47 ± 12% vs 54 ± 3%, p = 0.021) and higher LVEDP (14 ± 5 mmHg vs 10 ± 2 mmHg, p = 0.014). Using Pearson’s correlation increased partition coefficient, ECV and pre-contrast myocardial T1 were significantly correlated with elevated LVEDP: r = 0.385 (p = 0.021), r = 0.355 (p = 0.029) and r = 0.335 (p = 0.04), respectively. In dichotomized analysis elevated LVEDP (≥13 mmHg, N = 13) was associated with significantly higher partition coefficient (0.51 ± 0.1 vs 0.45 ± 0.06, p = 0.004), higher ECV (0.30 ± 0.06 vs 0.26 ± 0.03, p = 0.002) and higher pre-contrast myocardial T1 (1040 ± 123 ms vs 983 ± 44 ms, p = 0.045) when compared to those with normal LVEDP ( < 13 mmHg, N = 26). Among patients with elevated LVEDP (average 19 ± 3 mmHg) there were no significant differences in partition coefficient, ECV and pre-contrast myocardial T1 between those with preserved or reduced LVEF. In contrast, there was a lack of significant association between post-contrast myocardial T1 and LVEDP. Conclusions Increased contrast partition coefficient, ECV and precontrast myocardial T1 were significantly associated with elevated LVEDP in patients with nonischemic cardiomyopathy thereby supporting the link between extracellular volume expansion and myocardial diastolic dysfunction. Quantitative tissue characterization combined with hemodynamic assessment underscores the value of cardiac MRI in the evaluation of nonischemic cardiomyopathy.

Evaluating nonpolarizable nucleic acid force fields: A systematic comparison of the nucleobases hydration free energies and chloroform-to-water partition coefficients

Nucleic acid force fields have been shown to reproduce structural properties of DNA and RNA very well, but comparative studies with respect to thermodynamic properties are rare. As a test for thermodynamic properties, we have computed hydration free energies and chloroform-to-water partition coefficients of nucleobases using the AMBER-99, AMBER-gaff, CHARMM-27, GROMOS-45a4/53a6 and OPLS-AA force fields. A mutual force field comparison showed a very large spread in the calculated thermodynamic properties, demonstrating that some of the parameter sets require further optimization. The choice of solvent model used in the simulation does not have a significant effect on the results. Comparing the hydration free energies obtained by the various force fields to the adenine and thymine experimental values showed a very large deviation for the GROMOS and AMBER parameter sets. Validation against experimental partition coefficients showed good agreement for the CHARMM-27 parameter set. In view of mutation studies, differences in partition coefficient between two bases were also compared, and good agreement between experiments and calculations was found for the AMBER-99 parameter set. Overall, the CHARMM-27 parameter set performs best with respect to the thermodynamic properties tested here.

Targeted purification of natural products by orthogonal K-based countercurrent separations

Countercurrent separation (CS) is based on the differences in partition coefficients (K) of analytes distributed between a liquid stationary phase and a liquid mobile phase. The K value is not only an important theoretical parameter in CS, but also has much practical value. K values can be used to predict the CS profiles of analytes, assist in the selection and optimization of CS solvent systems (SSs), guide targeted separations, and enhance the reproducibility of purifications. In the present study we developed a quantitative 1H NMR (qHNMR)-based approach for simultaneous measurement of K values of multiple components directly from crude plant extracts. Furthermore, two-dimensional selectivity provided by a pair of orthogonal CS SSs was introduced in order to enhance the resolution of difficult-to-separate natural product congeners. Using the K values in optimized orthogonal SSs, a “K map” was created that guided the locating of the target compounds in a series of CS fractions (see figure). These methods were successfully employed in the targeted separation of marker compounds from Ginkgo biloba- and Camellia sinensis-based botanical dietary supplements.

Separation of two constituents from purple sweet potato by combination of silica gel column and high-speed counter-current chromatography

It is known that the choice of solvent system for high speed counter-current chromatography separation is of utmost importance. In this study, a simple and rapid thin layer chromatograph coupling with fluorometric (TLC-F) method has been used to determine the partition coefficient of target compounds in HSCCC solvent system. Two components, 6,7-dimethoxycoumarin and 5-hydroxymethyl-2-furfural were successfully separated from purple sweet potato extracts by successive sample injection for the first time, using n-hexane–ethyl acetate–methanol–water (1:2:1:1, v/v/v/v) as the solvent system. Additionally, statistical analysis showed that there was no significant difference in partition coefficient obtained by the TLC-F method and by HPLC, which demonstrated the usefulness of TLC-F method.

An experimental study of relative humidity effect on VOCs’ effective diffusion coefficient and partition coefficient in a porous medium

Most building materials are porous media. As a critical environmental factor, the influence of relative humidity on VOCs diffusion is still not well understood. In this study, VOC transport and sorption in a porous medium in the building materials (calcium silicate) were measured under three levels of relative humidity (25%, 50% and 80%) by using a dynamic dual chamber method. Tests were conducted for water-soluble compound (formaldehyde) and non-soluble compound (toluene). In addition, the transport of acetaldehyde, hexanal, benzaldehyde, butanol and decane through the calcium silicate were also tested at 50%RH to study the relationship between the effective diffusion coefficient ( D e), partition coefficient ( K ma) and the VOCs’ physical properties (molecular weight, vapor pressure and Henry’s law constant). Experimental results showed that: relative humidity in the 80%RH led to a higher partition coefficient for formaldehyde compared to 50%RH. However, between 25% and 50%RH, there was no significant difference in partition coefficient. Partition coefficient of toluene decreased with the increase of humidity due to competition of water molecules for pore surface area and the non-solubility nature of toluene. Relative humidity had no significant influence on the effective diffusion coefficient on both formaldehyde and toluene for the range of moisture conditions tested. The solubility of VOCs was found to correlate with the partition coefficient of VOCs. The partition coefficient of VOCs was not simply inversely proportional to the vapor pressure of the compound, but also increased with the increase of Henry’s law constant.

THE ROLES OF FAT AND PH ON THE DETECTION THRESHOLDS AND PARTITION COEFFICIENTS OF THREE COMPOUNDS: DIACETYL, δ‐DECALACTONE AND FURANEOL

ABSTRACT The effect of fat and pH on the best estimate threshold (BET) of three prominent dairy product flavor compounds with varying physicochemical properties: diacetyl (2, 3‐butanedione), δ‐decalactone and furaneol (2,5‐dimethyl‐4‐hydroxy‐3[2H]‐furanone), in water, oil and oil‐in‐water model emulsions (at 10 and 20% fat at neutral and acidified pH 5.5) were investigated. The headspace‐matrix partition coefficients (KHS/matrix) of each compound in the different matrixes were established using gas chromatography–mass spectrometry. The particle size of the emulsions was controlled. Fat had the largest impact on the BET and partition coefficients of δ‐decalactone followed by diacetyl (P ≤ 0.05). Fat content did not affect the BET value of furaneol (P &gt; 0.05) but some effects on partition coefficients were noted (P ≤ 0.05). BET values of the three compounds were unaffected by pH (P &gt; 0.05), but differences in partition coefficients (P ≤ 0.05) were noted for diacetyl and furaneol.PRACTICAL APPLICATIONSThis manuscript provides a better understanding of sensory detection thresholds as a result of partitioning of three flavor compounds that are different in physico‐chemical properties and are prominent in dairy product flavor. The acquired knowledge on these compounds may assist product developers in adjusting levels of flavor compounds in reduced fat products to achieve products similar in flavor properties to full fat products, considering the effect of fat and pH of the products on the compounds. Understanding the partition coefficients and detection threshold of one of the compounds studied, diacetyl, may also provide insights in ongoing debates on diacetyl and its safety levels in dairy products.

Effects of steam-heating processes on a stratified volcanic aquifer: Stable isotopes and dissolved gases in thermal waters of Vulcano Island (Aeolian archipelago)

We report on a comprehensive study of major-ion chemistry, dissolved gases, and stable isotopes measured in water wells at Vulcano Island since 1988. The work focuses on a quantitative model describing steam condensation and boiling phenomena in shallow water bodies. The model is based on the differences in partition coefficients between liquid water and vapor characterizing oxygen and hydrogen isotopes, as well as volcanic gases (CO 2, S species, and HCl). Based on both physical conditions of aquifers identified during drilling campaigns and the composition of the volcanic vapor, mass and enthalpy balances are applied in a multistep process of steam separation and condensation in shallower aquifers. By comparing the model results with measured data, we infer that (i) strong isotope enrichment observed in some shallow thermal waters can result from an increasing mass rate of condensing deep vapor, even in water meteoric in origin; (ii) the high CO 2 content measured in the fumarolic vapor during 1988–1993 affected the δ 18O value of the steam-heated water due to CO 2–H 2O isotope exchange; (iii) the high pCO 2 measured in the coldest and peripheral waters are explained by the progressive enrichment of this gas in the vapor phase during multistep boiling; and (iv) the high Cl − and SO 4 2−contents in the hottest waters can be attributed to the direct condensation (single-step) of volcanic vapor. The model also takes into account both the mass fluxes and the compositions of the involved endmembers (steam and shallow groundwater), which provides important inferences on the modifications observed or expected during periods of increasing mass and heat input from depth.

The transfer of neutral molecules, ions and ionic species from water to wet octanol

Partition coefficients for transfer from water to wet octanol have been set out for permanent ions, and for ionic species derived from neutral molecules by loss or acceptance of a proton. A previous equation for the partition of neutral compounds from water to wet octanol has been extended to include the partition of permanent ions, and ionic species; the only additional descriptors required are J(+) for cations and J(-) for anions. Fourteen cations and twelve anions are included in the equation. It is shown that differences in partition coefficients between neutral species and the corresponding ionic species, as log P(oct), are not at all constant. For carboxylic acids and the corresponding anion, differences are about 5.0 log units, for phenols and the corresponding anion differences range from 2.2 to 4.9 log units, and for amines and the corresponding protonated cations there is an enormous range of differences from 0.6 to 7.1 log units.

Form‐fill‐seal methodology for controlled encapsulation of small silver particles in hyperbranched polyglycidol

AbstractProduction of polar hyperbranched polymers and encapsulation of small particles in the hyperbranched polymers is like “forming” pouches and then “filling” these pouches. Modification of the end‐groups of the hyperbranched polymers with relative apolar groups is like “sealing” the pouches. In this article, we demonstrated that two methods depending on changed sequences, i.e., Form‐Fill‐Seal and Form‐Seal‐Fill methods resulted in different sized small particles with size‐depended properties. By using these approaches, small metal nano‐particles can be encapsulated inside polar microzones of dendritic‐star polymers taking advantage of the difference in partition coefficients instead of strong interactions between the dendritic polymers and ions. We used the methodology to produce small silver particles encapsulated in hyperbranched polyglycidol (HPG). The HPG was synthesized via anionic ring‐opening multibranching polymerization of glycidol. The “sealing” process was fulfilled by polymerization of ε‐caprolactone initiated from the end groups of HPG. In the Form‐Fill‐Seal approach, Ag+ was filled inside HPG, and then was sealed before reduction to Ag; whereas the “pouch” of HPG was sealed at first, and then Ag+ was filled inside HPG by diffusion in the Form‐Seal‐Fill approach. Mainly nanometer‐sized silver particles were formed by the Form‐Fill‐Seal approach, whereas silver clusters of several atoms were formed in the Form‐Seal‐Fill approach. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Local structure of Y and Ho in calcite and its relevance to Y fractionation from Ho in partitioning between calcite and aqueous solution

Among rare earth elements (REEs), the behavior of Y and Ho in most igneous activities is very close due to the similarity in their ionic radii, while Y fractionates from Ho in marine systems. In this study, in order to elucidate Y–Ho fractionation observed in marine systems in terms of structural chemistry, we examined Ho L III-edge and Y K-edge EXAFS study for two partitioning systems, namely, 1) calcite-aqueous solution (Y–Ho fractionation system) and 2) strong acid cation exchange resin-aqueous solution (non-Y–Ho fractionation system). The results of the EXAFS analysis did not show significant differences in interatomic distances to the most neighboring O atoms between Ho and Y for all the samples. However, it was found that the first shell Ho–O and Y–O distances in the Y–Ho doped calcite were shorter than those in the aqua ion. In contrast, the first shell Ho–O and Y–O distances in the Y–Ho doped resin were similar to those in the aqua ion. Previous studies have suggested that lanthanide (Ln) is more covalent due to 4f orbital participation in bonding relative to Y. Spectroscopic studies on various Ln 3+ complexes show that Racah parameters for 4f electron repulsion in Ln 3+ ions decrease with an increase in covalency of bonding of Ln 3+ ions with anionic ligands. Therefore, our EXAFS results suggest that Y–Ho fractionation in partitioning is possibly attributed to the difference of change in covalency associated with the ligand exchange between Y and Ho, which we have observed as differences in partition coefficients between calcite and aqueous solution.

Differential effects of aging on transport properties of anterior and posterior human sclera

The transport properties and composition of 44 pairs of human sclera, 37–91 years were compared. Solute transport, diffusion and partition coefficients of posterior sclera for solutes ranging in mass from 0·023–70 kDa were higher than those of anterior sclera; the posterior region was also more hydrated. The differences in partition coefficient between anterior and posterior sclera became more pronounced as solute molecular weight increased. Partition coefficients and hydration of both regions decreased with increasing age. Chondroitinase ABC digestion, which removed the majority of glycosaminoglycans, increased partition coefficients of both regions significantly. These results suggest that for regions of equal scleral thickness, neglecting the influence of vascular factors, drug delivery will be more readily achieved across the posterior sclera than the anterior sclera in the age group studied and that, for both regions, ease of delivery will decrease with decreasing age.

Synthesis, and in vitro and in vivo evaluation of a diphenylchlorin sensitizer for photodynamic therapy

This paper reports the synthesis of a new diphenylchlorin photosensitizer, 2,3-dihydro-5,15-di(3,5-dihydroxyphenyl)porphyrin (SIM01). The photodynamic properties, cell uptake and localization of SIM01 were compared with those of structurally related meso-tetra(hydroxyphenyl)chlorin (m-THPC). In vitro studies were conducted on rat glioma cells (C6) and human adenocarcinoma (HT-29), and in vivo studies on human colon adenocarcinoma cells (HT-29) and human prostate adenocarcinoma cells (PC3). Both dyes showed an absorption maximum at around 650 nm, with a molar extinction coefficient of 13 017 M −1 cm −1 for SIM01 and 22 718 M −1 cm −1 for m-THPC. Their capacity to generate singlet oxygen was identical, but differences in partition coefficients indicated that SIM01 was slightly more hydrophilic. In vitro, SIM01 was slightly more phototoxic than m-THPC for C6 cells (4.8 vs. 6.8 μg ml −1). However, phototoxicities were nearly identical for HT29 cells (0.45 μg ml −1 for 5 h incubation followed by 300 mW, 20 J cm −2). Pharmacokinetics in vivo in mice, as determined by fibre spectrofluorimetry, showed that the SIM01 fluorescence signal in the tumor was maximal between 6 and 12 h after injection, as compared to 72 h for m-THPC. With a 2 mg kg −1 dye dose and laser irradiation at 300 J cm −2 (650 nm, 300 mW), the optimal PDT response occurred when the interval between injection and irradiation was 6 h for SIM01 and 24 h for m-THPC. For SIM01 with 5 mg kg −1 injection, the optimal PDT response occurred with a 12 h delay and with the same irradiation parameters as described above, in this case the tumor response showing 40% growth. Considering the tumor volume doubling time, the value was 6.5 days in the control group and increased to 13.5 days with SIM01. Thus, SIM01 may be a powerful sensitizer characterized by strong in vitro and in vivo phototoxicity and faster tissue uptake and elimination than m-THPC.

Partition coefficients of charged and uncharged local anesthetics into dipalmitoylphosphatidylcholine bilayer membrane: estimation from pH dependence on the depression of phase transition temperatures

Effects of the local anesthetics, dibucaine, bupivacaine and lidocaine on the phase transition temperatures of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane were studied by the optical method. We focus our attention on pH dependence of the depression of main transition and pretransition temperatures. The temperatures of both transitions of DPPC bilayer membrane were depressed by the addition of anesthetics; the higher the value of pH, the larger the depression of main transition temperature and/or pretransition temperature by anesthetics. By extending the colligative thermodynamic framework to the depression of main transition temperature by an anesthetic, we can estimate the differential partition coefficient, which is defined by the difference in partition coefficients of an anesthetic into the ripple gel and liquid crystal phases. The difference in partition coefficient between the lamellar and ripple gel phases can also be estimated from the depression of pretransition temperature. Since the differential partition coefficients include both contributions of the charged and uncharged anesthetics, we could estimate the partition coefficients of the charged and uncharged anesthetic into the membranes from the pH dependence of differential partition coefficients. The liquid crystalline membrane of DPPC bilayer was more receptive to the uncharged local anesthetics than the charged species. The partition coefficients of the charged and uncharged anesthetics into the liquid crystalline phase of DPPC bilayer membrane were 3540 and 249 000 (for dibucaine), 1120 and 83 900 (for bupivacaine), 256 and 11 700 (for lidocaine), respectively. The transfer free energy of uncharged anesthetics from the aqueous phase to the liquid crystalline membrane was well correlated to the local anesthetic potency.

Solvent effect on K+ to Na+ ion mutation: a Monte Carlo simulation study

Monte Carlo simulation studies of statistical perturbation theory (SPT) have been carried out to investigate the solvent effects on the relative free energies of solvation and the difference in partition coefficients (logP) for K+ to Na+ ion mutation in the several solvents. We compared the relative free energies for interconversion of K+ to Na+, in H2O (TIP4P) in this study with those published works, that in H2O (TIP4P) is −16.55kcal/mol in this study, those of the published works are −17.6, −17.3 and −17.31kcal/mol and that of the experiment is −17.6kcal/mol, respectively. Comparing the relative free energies for interconversion of K+ to Na+, in CH3OH in this study with those published works, that in CH3OH is −18.08±0.28kcal/mol in this study, that of molecular dynamic simulation is −19.6±0.4kcal/mol and that of the experimental work is −17.3kcal/mol, respectively. There is good agreement among the several studies if we consider both methods of obtaining the solvation (or hydration) free energies and the standard deviations. For the present K+ and Na+ ions, the relative free energies of solvation vs Born's function of solvents are decreased with increasing Born's function of solvent except for CH3OH, THF and MEOME. There is also good agreement between the calculated structural properties in this study and the computer simulation, ab initio and experimental works.

Diffusion of (de)acylated antibiotic A40926 in alginate and carrageenan beads with or without cells and/or soybean meal.

Effective diffusion coefficients (D(e)) of antibiotic A40926 and its deacylated derivative were determined in Ca-alginate (2% wt/wt) and kappa-carrageenan (2.6% wt/wt) gel beads with or without immobilized Actinoplanes teichomyceticus cells and/or soybean meal (SBM). The method used was based on transient concentration changes in a well-stirred antibiotic solution in which gel beads, initially free of solute, were suspended. Unsteady-state diffusion in a sphere was applied and D(e) determined from the best fit of experimental data. A40926 showed markedly different diffusion characteristics than its deacylated derivative. Diffusivity of deacyl-A40926 in alginate or carrageenan gel beads was six to seven times that of A40926. Large differences in partition coefficients (Kp) were also found. In case of beads without additions, A40926, in contrast to deacyl-A40926, strongly partitioned to the liquid phase. Introduction of SBM and/or mycelium in the gel beads decreased the effective diffusivity of deacyl-A40926, but increased its partitioning to the solid phase. Our findings indicate that a relatively moderate structural change of a lipoglycopeptide molecule could lead to a major change in its diffusion/partition characteristics.