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Solution thermodynamics of alkyl p-aminobenzoates.

Equilibrium solubilities of the first four homologous alkyl p-aminobenzoate esters were determined in methanol, ethanol, and 1-propanol at 25, 33, and 40 degrees; the esters and the alcohols comprise separate homologous series. The solution process of a solute may be considered to be the summation of two sequential steps, melting and mixing, and the magnitude of solubility depends upon temperature and the extent of interactions between solute and solvent molecules. Quantitative solute concentrations, obtained from spectrophotometric analysis, were converted to mole fractions. Statistical analysis of the logarithmic mole fraction solubilities of the aminobenzoates, which were linear with respect to both reciprocal absolute temperature and the logarithm of absolute temperature, generated enthalpies and entropies of solution, respectively. The heats of fusion and the melting points of these aminobenzoates were determined to calculate their ideal solubilities. Excess free energies and partial molal free energies of each solution were calculated from the activity coefficients of the solutes; the thermodynamic elements for these systems are discussed.

Aminobenzoates↗

Solubility profiles and thermodynamics of parabens in aliphatic alcohols.

The solubility of a series of compounds was determined in a wide polarity spectrum of normal aliphatic alcohols over a limited temperature range. The solutes chosen were the methyl through n-butyl p-hydroxybenzoates, several of these being useful preservatives. Solubility profiles were determined for these compounds, and the effect of temperature upon their solubility behavior was investigated. The solubility of the solutes is expressed in several concentration notations; mole fraction plots showed a variable twin peak array as a function of the dielectric constant for the solutes studied. Since heats of fusion were available and data were generated as a function of temperature, thermodynamic parameters for these systems could be calculated. The relationship of these parameters to multiple solubility peak array is discussed.

Alcohols↗

Thermodynamic relationship between alpha- and beta-forms of crystalline progesterone.

Thermodynamic properties such as the latent heat of fusion, aqueous solubility, heat of solution, and interchange energy with water were determined for single crystals of progesterone in alpha- and beta-forms. The differences in the properties between the polymorphic crystals arise from a dissimilar mode of molecular packing, rather than of molecular conformation, in the unit cells, as reflected in the IR spectral and X-ray crystallographic results..

Crystallization↗

Prostaglandin prodrugs VI: structure-thermodynamic activity and structure-aqueous solubility relationships.

Solubilities in isoctane and water were determined for several C1-phenolic esters of prostaglandin F2 alpha and prostaglandin E2 and acetates having the same phenol moiety. Linear free energy relationships for solubility among the series were observed with slopes of approximately 1. These results suggest that the contributions of the phenyl substituent to the free energies of these processes are similar in the three series, even though the structure of the acyl moiety is varied. In addition, aqueous solubility was separated into two thermodynamic components, reflecting transfer from the solid phase to an inert solvent and transfer from the inert solvent to water, to evaluate the relative effects of various substituents on the escaping tendency of the drug from the solid phase and on solution interactions. It was found that polar, hydrogen-bonding functional groups in many cases do not bring about increased water solubility because of a corresponding increase in intermolecular interaction in the solid phase.

Prostaglandins↗

Kinetics and thermodynamics of interfacial transfer.

The kinetic barrier against the transport of methyl and ethyl nicotinates across the water-isopropyl myristate interface has been studied as a function of temperature using a rotating diffusion cell. The temperature dependence of the interfacial transfer kinetics has enabled calculation of the thermodynamic parameters for the process. It is evident from the results that, for the transferring solutes considered, the activation energy barrier is enthalpic, because there is a large positive entropy for transfer into the interfacial region.

Diffusion↗

Dissolution and partition thermodynamic functions of some nonsteroidal anti-inflammatory drugs.

Solubility values of a selected group of nonsteroidal anti-inflammatory drugs have been determined in water and 1-octanol as a function of temperature. Thermodynamic functions of dissolution and partition have been calculated and discussed with respect to various physical parameters of each solute and the two solvents. The calculated solubility values show good agreement with the experimental values. The analysis of the experimental solubility values of these compounds in terms of solid-state contribution and solute-solvent interaction suggests the different importance of these parameters in promoting solubility of solid nonelectrolytes.

Anti-Inflammatory Agents↗

Thermodynamic proton-ligand and metal-ligand stability constants of some drugs.

The thermodynamic proton-ligand (pKa) and metal-ligand stability constants of clioquinol, clofibrate, nitrofurazone, and tetracycline with Cu2+, Zn2+, Mn2+, Mg2+, and Ca2+ have been determined at 35 degrees C in 50% ethanol-water media. An empirical pH correction for mixed-aqueous media has been applied. The metal-ligand stability constants were determined by following the Bjerrum Calvin titration technique as applied by Agrawal to mixed-aqueous solvents. The effect of the basicity of the ligand and the order of stability constants is discussed. The stability constants of the divalent metals follow the order: Cu2+ greater than Zn2+ greater than Mn2+ greater than Mg2+ greater than Ca2+ with all the drugs.

Buffers↗

Determination of the thermodynamic ionization constants of cefroxadine.

The values of the thermodynamic ionization constants of the carboxylic (pK = 3.30 +/- 0.02) and amine (pK = 7.00 +/- 0.06) groups of cefroxadine were determined at 35.0 degrees C using potentiometric data. The apparent ionization constants of these groups were also determined at 35.0 degrees C, and at different values of ionic strength.

Cephalosporins↗

Percutaneous absorption of physostigmine: optimization of delivery from a binary solvent by thermodynamic control.

A series of binary vehicles was used to deliver physostigmine across dermatomed human skin. The vehicles consisted of isopropyl myristate (IPM) and isopropyl alcohol (IPA) mixed in various volume fractions. The kinetics of penetration is conveniently considered as the sum total of two contributing effects: a "push" process resulting from the excess free energy (delta EG) of the penetrant in the donor vehicle, and a "pull" process resulting from the effect of IPA and IPM on the skin barrier. The inverse ratio of the solubility of the drug in a given vehicle to that in pure IPA was used to estimate the relative delta EG, hence the relative "push" effect. The solubility of physostigmine was highest in pure IPA (delta = 11.5), lowest in pure IPM (delta = 8.5), and intermediate in their various mixtures. But the permeability coefficient (Kp) of physostigmine was highest when delivered from a 1:9 (v/v) solution of IPA:IPM and a calculated delta y = 8.8. A further increase in the volume fraction of IPA caused an opposite decrease in the Kp values of physostigmine. The "steady-state" flux (Jss) of IPA from the same vehicle was lowest at a volume fraction of 1:9 and highest at one of 1:1 IPA:IPM. Thus, the maximal physostigmine penetration enhancing effect of IPA occurs at the lowest flux of IPA found in the present series. This indicates that the "pull" process ascribed to the presence of IPA in the barrier membrane is not important enough to outweigh the decrease in delta EG of physostigmine following an increase in the volume fraction of IPA in the donor vehicle, or that an excess of IPA in the barrier is not conducive to further enhancement of physostigmine diffusivity across the barrier. Optimized percutaneous delivery of physostigmine is possible by thermodynamic control of the penetration process.

1-Propanol↗

Evaluation of thermodynamic ionization constants by computation of spectrophotometric and potentiometric experimental data obtained simultaneously from a flow system.

A method is proposed for the direct and simultaneous determination of the thermodynamic ionization constants of bifunctional substances, with (microscopic) and without overlap in the ionizations, with computational treatment of spectrophotometric and potentiometric experimental data obtained simultaneously in a flow system. For monofunctional substances, potentiometric data are enough. The data are obtained at very low values of ionic strength, which is variable throughout the experiment because no inert electrolyte is added. The MICROTER program, written in FORTRAN 77, is based on an algorithm of mathematical optimization with a controlled-descent movement. The ionization constants of the following substances of pharmacological interest were determined: cysteine, penicillamine, ofloxacin, and norfloxacin (bifunctional with overlap); cephalexin and cephapirin (bifunctional without overlap); and tolazoline, naphazoline, and oximetazoline (monofunctional).

Adsorption↗

A thermodynamic approach to the binding mechanisms of cefotaxime to serum albumins.

The interaction between cefotaxime and the serum albumin of several mammalian species (swine, rabbits, and sheep) at the albumin concentration of 5 x 10(-5) M was studied. Ultrafiltration and spectrophotometric determination of the free antibiotic in the filtrate were used. Binding percentages were determined, and the binding constants and number of sites at various temperatures were calculated. An increase in binding constants, especially in sheep albumin, and an increase in the number of sites from two to three were observed when compared to the results obtained at the physiological albumin concentration. The thermodynamic parameters of interaction varied between the following values: change in Gibbs energy, between -5.7 and -6.4 kcal.mol-1; change in enthalpy, between -6.7 and -9.6 kcal.mol-1; and change in entropy, between -3.1 and -11.2 entropy units. The binding constants increased considerably as the ionic strength of the solution decreased although the number of binding sites remained unchanged. These results indicate the existence of ionic and hydrogen bonds. The possibility of a small contribution from hydrophobic bonds cannot be ruled out.

Animals↗

Thermodynamic analysis of energy dissipation by pharmaceutical tablets during stress unloading.

A thermodynamic analysis of the energy transformations occurring within pharmaceutical tablets during the unloading phase of compaction was performed on Avicel, calcium phosphate, acetaminophen, and calcium oxalate. This analysis was based on viscoelastic stress data collected using an instrumented rotary press and was conducted for the purpose of determining the extent and nature of energy release, beyond that of force displacement, during this phase of compaction. The four materials investigated were selected to reflect a range of compaction properties, and the viscous vs force-displacement energy distributions were seen to be consistent with their brittle vs plastic character. Magnesium stearate, added in various concentrations up to 4% w/w, was found to act both as an internal lubricant for particle-particle slipping and as a moderator of interparticulate bonding.

Acetaminophen↗

A new pH-metric methodology for the determination of thermodynamic inclusion constants of guest/cyclodextrin complexes.

A new methodology of pH-metric data treatment was developed to extract the stoichiometry and the thermodynamic association constants of guest-cyclodextrin inclusion complexes in dilute aqueous solution when the guest is a participant in an acid-base equilibrium. pH-metric titration curves in the presence of cyclodextrin (CD) were treated by a curve-fitting technique according to a nonlinear least-squares regression. Equations corresponding to the different kinds of acid-base pairs (AH/A-, BH+/B) and stoichiometries (1:1 and 1:2) were established. The methodology was validated by studying the 5-phenylbarbituric acid complexation with beta-CD and the 4-cyanobenzoic acid complexation with alpha-CD. Then it was applied to chlorpromazine. Both the acid form (constant K1 = 3260) and the base form (constant G1 = 13,100) gave complexes with beta-CD according to 1:1 stoichiometry.

Barbital↗

Thermodynamics, the structure of integral membrane proteins, and transport.

Membranes are structures whose lipid and protein components are at, or close to, equilibrium in the plane of the membrane, but are not at equilibrium across the membrane. The thermodynamic tendency of ionic and highly polar molecules to be in contact with water rather than with nonpolar media (hydrophilic interactions) is important in determining these equilibrium and nonequilibrium states. In this paper, we speculate about the structures and orientations of integral proteins in a membrane, and about how the equilibrium and nonequilibrium features of such structures and orientations might be influenced by the special mechanisms of biosynthesis, processing, and membrane insertion of these proteins. The relevance of these speculations to the mechanisms of the translocation event in membrane transport is discussed, and specific protein models of transport that have been proposed are analyzed.

Biological Transport, Active↗

Study of the mechanism of enantioseparation part VI: thermodynamic study of HPLC separation of some enantiomers of phenylcarbamic acid derivatives on a (S,S) Whelk-O 1 column.

The enantiomers of thirteen 2-, 3-, and 4-alkoxyphenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino)methyl]ethyl ester were separated on a (S,S) Whelk-O 1 CSP column isothermally in the range of 0-50 degrees C at 10 degrees C increments, using methanol/ water (90/10, v/v) containing 17.5 mmol L(-1) acetic acid and 14.36 mmol L(-1) triethylamine as a mobile phase. The dependence of the natural logarithms of retention and selectivity factors (In k, In alpha, respectively) on the inverse of temperature, 1/T, was used to determine thermodynamic data of enantiomers of alkoxysubstituted phenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino) methyl]ethyl esters. Enthalpyentropy compensation plots showed that all of the compounds in this study separate via the same enthalpy-driven chiral recognition mechanism.

Acetic Acid↗

Extended thermodynamic approach to ion interaction chromatography. A mono- and bivariate strategy to model the influence of ionic strength.

Recent breakthroughs in the theory of ion interaction chromatography (IIC) permit new analyses of the dependence of retention on different interdependent factors. The influence of the ionic strength / on the surface potential, the Donnan effect, and salting effects are taken into account to model the chromatographic behaviour of charged analytes in IIC. The most reliable experimental results found in the literature were used to test the retention equations that were developed following both a monovariate (/ changes as the concentration of H, ion interaction reagent, changes) and a bivariate (/ changes because of the simultaneous variation of H and of the background electrolyte concentrations) approach. The present extended thermodynamic model builds on the sound intuition of the electrostatic approach and proves to provide the most successful and exhaustive quantitative explanation of experimental evidence. It is also able to rationalise the less extensive agreement between the pure electrostatic approach predictions and experimental results. The adequacy of the model is supported by physically reliable estimates of the adjustable constant (ion-pair constants, deltaG degrees). Moreover statistical practice demonstrates that all the adjustable parameters (three at most) are statistically significant. A linear, zero crossing function with unit slope is obtained when k(pred) is plotted against k(exp). The mean percent error between k(pred) and k(exp) is 4.5% at most. In the absence of H the present retention equation reduces, as expected, to the relationship that describes the influence of / on the retention behaviour in reversed-phase liquid chromatography.

Chromatography↗

Adsorption kinetics and thermodynamics of acid dyes on a carboxymethylated chitosan-conjugated magnetic nano-adsorbent.

The monodisperse chitosan-conjugated Fe(3)O(4) nanoparticles with a mean diameter of 13.5 nm were fabricated by the carboxymethylation of chitosan and its covalent binding onto Fe(3)O(4) nanoparticles via carbodiimide activation. The carboxymethylated chitosan (CMCH)-conjugated Fe(3)O(4) nanoparticles with about 4.92 wt.-% of CMCH had an isoelectric point of 5.95 and were shown to be quite efficient as anionic magnetic nano-adsorbent for the removal of acid dyes. Both the adsorption capacities of crocein orange G (AO12) and acid green 25 (AG25), as the model compounds, decreased with increasing pH, and the decreasing effect was more significant for AO12. On the contrary, the increase in the ionic strength decreased the adsorption capacity of AG25 but did not affect, obviously, the adsorption capacity of AO12. By the addition of NaCl and NaOH, both AO12 and AG25 could desorb and their different desorption behavior could be attributed to the combined effect of pH and ionic strength. From the adsorption kinetics and thermodynamics studies, it was found that both the adsorption processes of AO12 and AG25 obeyed the pseudo-second-order kinetic model, Langmuir isotherm, and might be surface reaction-controlled. Furthermore, the time required to reach the equilibrium for each one was significantly shorter than those using the micro-sized adsorbents due to the large available surface area. Also, based on the weight of chitosan, the maximum adsorption capacities were 1 883 and 1 471 mg x g(-1) for AO12 and AG25, respectively, much higher than the reported data. Thus, the anionic magnetic nano-adsorbent could not only be magnetically manipulated but also possessed the advantages of fast adsorption rate and high adsorption capacity. This could be useful in the fields of separation and magnetic carriers. [formula in text].

Acids↗

31P NMR studies of the thermodynamics and kinetics of the creatine kinase reaction.

The thermodynamic and kinetic parameters of the reaction catalyzed by creatine kinase (CK) were measured in vitro in the temperature range 13 to 35 degrees C, using 31P NMR spectroscopy, including magnetization transfer methods. The apparent equilibrium constant of the reaction and the associated enthalpy for the formation of ATP at 35 degrees C, pH 8.2, and excess [Mg2+] were 3.5 x 10(9) M-1 and -2.4 +/- 0.5 kcal/mol, respectively. The rates at equilibrium at 35 degrees C catalyzed by 1 unit/ml CK were 12.4 and 10.7 microM/s at pH 7 and 8, respectively. The rate constants per 1 unit CK/1 ml at 35 degrees C, pH 7, were 1.3 x 10(8) s-1 M-2 and 9.9 x 10(-3) s-1 M-1 in the direction of ATP and PCr formation, respectively. The activation energies in both directions were similar and corresponded to 15 +/- 2 kcal/mol at pH 7 and 17.5 +/- 1.5 kcal/mol at pH 8. Comparison of in vivo results with the above in vitro data may provide information regarding the activity and kinetics of the CK reaction.

Creatine Kinase↗