Biomedical subjects

K A Connors

Publications and source records attributed to K A Connors.

At least 19 recordsLinked to original sources

PubMed1995

Population characteristics of cyclodextrin complex stabilities in aqueous solution.

Binding constants (K11) of 1:1 complexes of alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin with many substrates (guests) were collected from published sources and subjected to statistical analysis. All systems refer to 25 +/- 5 degrees C and aqueous solution. The frequency distributions of log K11 are satisfactorily described by normal distributions with the following parameters (n = number of complexes, mu = population mean, sigma = population standard deviation): alpha-cyclodextrin, n = 663, mu = 2.11, sigma = 0.90; beta-cyclodextrin, n = 721, mu = 2.69, sigma = 0.89; gamma-cyclodextrin, n = 166, mu = 2.55, sigma = 0.93. Stabilities of pairs of cyclodextrin complexes with a common substrate are not precisely correlated, but they do not appear to be wholly independent quantities. The stabilities of alpha-cyclodextrin complexes are consistent with a recent interpretation of solvent effects on alpha-cyclodextrin complex stabilities.

Cyclodextrins↗

PubMed1994

Solvent effects on chemical processes. 8. Demethylation kinetics of aspartame in binary aqueous-organic solvents.

The kinetics of demethylation of aspartame were studied in binary aqueous-organic solvent mixtures at 25 degrees C under two solution conditions, namely 1.0 M HCl (pH 0.28 in water) and carbonate buffer (pH 10.1 in water). Under these conditions solvent effects on the acid dissociation constants of aspartame do not complicate the interpretation of the kinetics. The organic cosolvents were acetone, acetonitrile, dimethyl sulfoxide, dioxane, tetrahydrofuran, and methanol. The observed kinetic solvent effects were modest in magnitude, not exceeding a factor of 3 in rate constant, relative to the fully aqueous solution. The rate changes included both increases and decreases, and in some solvent mixtures extrema were observed. It is concluded that at least two contributory factors, identified as an electrostatic (dielectric constant) effect and a solvation effect, must be operating to produce the observed kinetic solvent effects.

Acetone↗

PubMed1993

Solvent effects on chemical processes. V: Hydrophobic and solvation effects on the solubilities of substituted biphenyls in methanol/water mixtures.

A phenomenological model that permits solvent effects to be separated into general medium effects (the solvophobic effect) and solvation effects is applied to the solubility of a series of biphenyl compounds in methanol/water mixtures. The parameters of the model (gA, K1, and K2, K1 and K2 are equilibrium constants for solvation and gA describes the general medium contribution) were evaluated from the nonlinear regression of the model equation to the data. It was found that the surface tension curvature factor (g) was 0.37, that A represents the hydrophobic (nonpolar) surface area of the solute molecule, and that K1 and K2 were 2.53 and 1.77 (means for solutes in methanol/water), respectively. These results permit solvent effects on solubility in methanol/water to be predicted and they refine the interpretation of the solvent effect model.

Biphenyl Compounds↗

PubMed1993

Demethylation kinetics of aspartame and L-phenylalanine methyl ester in aqueous solution.

The kinetics of demethylation of aspartame and L-phenylalanine methyl ester were studied in aqueous solution at 25 degrees C over the pH range 0.27-11.5. The pseudo-first-order rate constant for aspartame was resolved into individual contributions from methyl ester hydrolysis and diketopiperazine formation. pH-rate profiles were quantitatively described by chemically reasonable kinetic schemes. Aspartame is maximally stable at pH 4 (t90 = 53 days at 25 degrees C); phenylalanine methyl ester, at pH 3. The potentiometrically measured pKa values were pKa1 3.19 and pKa2 7.87 for aspartame and pKa 7.11 for phenylalanine methyl ester.

Aspartame↗

PubMed1992

Misoprostol dehydration kinetics in aqueous solution in the presence of hydroxypropyl methylcellulose.

Misoprostol (Searle), and E1-type prostaglandin, is known to be stabilized in the form of a solid dispersion with hydroxypropyl methylcellulose (HPMC), yet no evidence has been found for specific intermolecular interactions. In the present study, the dehydration kinetics of this prostaglandin were studied in aqueous solution in the absence and the presence of HPMC. The dispersion of the drug with HPMC, when dissolved in pH 7.66 aqueous solution, exerted a small but significant stabilizing effect. A possible interpretation of this kinetic result, together with lack of evidence for complex formation in both the solid and solution states, may be that HPMC exerts its stabilizing effect by physically limiting the access of water the prostaglandin through an entanglement of the prostaglandin in the polymer environment, the diffusion of drug away from the polymer being slow on the time scale of the dehydration kinetics.

Algorithms↗

PubMed1992

Solvent effects on chemical processes. I: Solubility of aromatic and heterocyclic compounds in binary aqueous-organic solvents.

The standard free energy change (delta G0) for equilibrium dissolution in binary solvent mixtures is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The general medium effect is given by gA gamma, where g is a curvature correction factor to the surface tension (gamma) and A is the molecular cavity surface area. A new feature is the definition of gamma to be that value appropriate to the equilibrium mean solvation shell composition. The solvation effect is modeled by stoichiometric stepwise competitive equilibria between the two solvent components for the solute. The intersolute effect includes the crystal energy and solution phase interactions. In this work, water was solvent component 1, and various miscible organic cosolvents served as solvent component 2. Relating all data to the fully aqueous solution gives an explicit expression for delta M delta G0, the solvent effect on the free energy change, as a function of the mole fractions x1 and x2. This function is a binding isotherm. Nonlinear regression leads (for a two-step solvation scheme) to estimates of the solvation exchange constants K1 and K2 and the parameter gA. This relationship was applied to 44 systems comprising combinations of 31 solutes and eight organic cosolvents. Curve fits were good to excellent, and most of the parameter estimates had physically reasonable magnitudes.

Chemical Phenomena↗

PubMed1988

Studies on adsorptiochromism. II: Diffuse reflectance spectroscopy of adsorptiochromic spiropyrans adsorbed to some pharmaceutically useful solids.

The colored powders produced by the adsorption of four adsorptiochromic spiropyrans to many solids (silica gel, silicic acid, fumed silica, alumina, microcrystalline cellulose, talc, titanium dioxide) were examined by diffuse reflectance spectroscopy. The reflectance spectra were dominated by two bands, one at 550 nm and the other in the range 400-500 nm, often at 472 nm. Plots of the Kubelka-Munk function [F(R' infinity)] against g, the coverage expressed in nmol/m2, were linear at very low g and approached a limiting value independent of g at high coverage. The color formation upon adsorption terminates at coverages much lower than the maximum binding capacity of the solid. The slope of the plot of F(R' infinity) against g, at low g (denoted f0), appears to be sensitive to the scattering properties of the solid. For a single solid (silica gel), comparison of f0 for adsorptiochromic adsorbates with f0 for permanent dyes allowed estimates to be made of the fraction of adsorbed spiropyran in the colored form on the surface.

Benzopyrans↗

PubMed1987

Chromogenic reactions of tertiary amines with polycarboxylic acids and acetic anhydride: carbon suboxide as the reactive species in the malonic acid reagent.

Analytical methods based on the title reactions are reviewed, and the malonic acid-acetic anhydride system was selected for detailed study. It is postulated that carbon suboxide, O = C = C = C = O, formed by the action of acetic anhydride on malonic acid, is the effective reactive species in this system. Carbon suboxide was prepared and identified, and spectrophotometric observations of its reactions with tertiary amines are described. Aliphatic and aromatic tertiary amines generate colored products upon reaction with carbon suboxide in the presence of acetic anhydride. It was found that aliphatic tertiary amines form colors upon reaction with carbon suboxide in the absence of acetic anhydride, whereas aromatic tertiary amines require the presence of acetic anhydride.

Acetates↗

PubMed1987

Studies on adsorptiochromism. I: Binding of adsorptiochromic spiropyrans to some pharmaceutically useful solids.

The adsorption of four adsorptiochromic spiropyrans to many solids (silica gel, silicic acid, fumed silica, alumina, microcrystalline cellulose, talc, titanium dioxide) was studied at 25 degrees C from cyclohexane solution. Nineteen adsorption isotherms were determined; and the binding data were fitted to the Langmuir equation. A model for binding of adsorptiochromic substances is described, and the parameters of the model are related to the experimental binding constant K.

Adsorption↗

PubMed1987

Adsorption of inorganic and organic ions to polycarbophil as a means of sustained-release dosage formulation.

The adsorption and desorption of drugs and inorganic ions to and from polycarbophil (PC), a polymer, were investigated to determine if PC would be a suitable carrier for sustained-release dosage formulations. Both in vitro and in vivo experiments with a polycarbophil-atropine sulfate complex demonstrated the gradual-release properties of this system. Adsorbed Cr3+ ions, like atropine, are released slowly. In contrast, 51CrO4(2-) ions are predominantly bound in an irreversible manner. A third group of drugs minimally adsorbed to PC under the conditions studied. We conclude that PC under both in vitro and in vivo conditions is able to bind certain ions and drugs and then release them over a period of time in a predictable and repeatable manner.

Acrylic Resins↗

PubMed1987

Estimation of surface polarity of silicas by absorption spectroscopy of glycerin suspensions of adsorbed 6-nitrobenzoindolinopyran.

The title compound (6-NO2-BIPS) is adsorptiochromic, becoming colored upon adsorption to a polar surface. Powders of 6-NO2-BIPS adsorbed to silica gel or silicic acid are suspended in glycerin, and the absorption spectrum of the adsorbate is recorded by conventional absorption spectroscopy. The wave number of maximum absorption is related to the effective surface polarity by v*/cm-1 = 90.85 Z + 11,571, where Z is the Kosower polarity measure. Silica surface polarity corresponds to Z = 86-89.

Absorption↗

PubMed1984

Improved competitive indicator methods for the study of alpha-cyclodextrin complexes.

The competitive indicator method for studying molecular complexes is extended to systems forming 1:1 (SL) and 1:2 (SL2) complexes of substrate (S) and ligand (L). A modification is described for slightly soluble substrates, in which the presence of solid substrate establishes a constant concentration of uncomplexed substrate. These methods are applied to complexes of alpha-cyclodextrin with some aromatic substrates, with methyl orange as the indicator in acid solution; nitrazine yellow is introduced as an indicator for these studies in basic solution.

Chemical Phenomena↗

PubMed1983

Kinetic study and analytical application of the hexadecyltrimethylammonium bromide-catalyzed reaction of 1-fluoro-2,4-dinitrobenzene with amines.

Arylation of amines by reaction with 1-fluoro-2,4-dinitrobenzene is catalyzed by micelles of cetrimonium bromide. This catalysis has been exploited to reduce the analysis time in the spectrophotometric determination of amines as their dinitrophenyl derivatives. The kinetics of the catalysis were studied for the five amines: alanine, phenylalanine, aniline, 4-methylaniline, and 4-methoxyaniline. The dependence of rate constant on surfactant concentration can be quantitatively accounted for by Berezin's model, in which uptake of the amine and the 1-fluoro-2,4-dinitrobenzene by the micelle is described as a partitioning phenomenon for both species. An alternative model is developed in which one reactant partitions into the micellar phase and the other binds to the micelle with 1:1 stoichiometry; the two models are formally equivalent. Intrinsic catalytic rate constants and binding constants were evaluated. About one-third to one-half of the maximum observed micellar acceleration is attributed to a true micellar catalysis, the remainder being ascribed to an increase in local reactant concentrations in the micelle.

Amines↗

PubMed1983

Kinetics and mechanism of hydroxy compound cinnamoylation in acetonitrile catalyzed by N-methylimidazole and 4-dimethylaminopyridine.

The kinetics of reaction of the acylating agents trans-cinnamic anhydride and trans-cinnamoyl chloride with the hydroxy compounds n-propyl alcohol and water in the presence of N-methylimidazole and 4-dimethylaminopyridine were studied spectrophotometrically in acetonitrile solution at 25 degrees. The acid chloride reacted via the intermediate formation of the N-acyl catalyst, which underwent general base-catalyzed reaction with the hydroxy compound. The anhydride did not form the N-acyl intermediate, but instead underwent direct general base catalysis. In the presence of water, all systems formed the N-acyl intermediate. The mechanistic route followed by the system was determined by the nucleophilicity of the catalyst, the ability of the leaving group, and the polarity of the solvent.

1-Propanol↗

PubMed1983

Solvent effects on the cinnamoylation of n-propyl alcohol catalyzed by N-methylimidazole and 4-dimethylaminopyridine.

The kinetics of reaction of trans-cinnamic anhydride or trans-cinnamoyl chloride with n-propyl alcohol, catalyzed by N-methylimidazole or 4-dimethylaminopyridine, were studied spectrophotometrically at 25 degrees in methyl ethyl ketone, ethylene dichloride, methylene chloride, and toluene. The acid chloride reacted in all solvents via the intermediate formation of the N-acyl catalyst, which underwent reaction with the alcohol catalyzed by another molecule of the base. The anhydride did not form the intermediate in any of the solvents, but underwent direct general base catalysis. The rate of the anhydride reactions was not sensitive to solvent polarity, whereas the rate of the chloride reactions tended to increase as the solvent polarity decreased. A kinetic analysis is given of the effect of ion-pair formation on the kinetics of acyl transfer in systems where the charged N-acyl catalyst intermediate is formed.

1-Propanol↗

PubMed1983

Stability constants for complex formation between alpha-cyclodextrin and some amines.

Complex formation of alpha-cyclodextrin with 15 amines (including seven 4-substituted anilines) was studied by the potentiometric method, supplemented by direct UV spectrophotometry and a competitive indicator spectrophotometric method. The data were analyzed in terms of 1:1 and 1:2 complexes (amine-cyclodextrin ratios) and the stability constants K11a, K12a, K11b, and K12b were evaluated; the subscripts indicate the stoichiometry and conjugate acid-base form. For all amines K11b was greater than K11a and K12a was 0. On the basis of the relationship of complex stability to amine structure, it was concluded that the primary binding site in anilines is the 4-substituent.

Amines↗

PubMed1983

Complex formation between alpha-cyclodextrin and 4-substituted phenols studied by potentiometric and competitive spectrophotometric methods.

Stability constants for complex formation between alpha-cyclodextrin and the conjugate acid and base forms of nine phenols were measured in aqueous solution at 25 degrees. The potentiometric method, in which the apparent acid dissociation constant of the phenol is measured as a function of cyclodextrin concentration, was supplemented by a modified version of a competitive spectrophotometric methyl orange method. For all phenols, the 1:1 stability constant for the conjugate base form (K11b) was larger than K11a for the conjugate acid form. Finite K12b values were found for phenols whose 4-substituents could tolerate a positive charge by electron delocalization. Complex stability, as measured by K11a and K11b, increases with electron density and polarizability at the 4-substituent. It is concluded that the 4-substituent is the sole or predominant site of binding for both the conjugate acid and base forms of the phenols. The general result that K11b is greater than K11a for any phenol is accounted for by relative delocalization of charge in the anion and neutral species.

Binding Sites↗

PubMed1982

Potentiometric study of molecular complexes of weak acids and bases applied to complexes of alpha-cyclodextrin with para-substituted benzoic acids.

The theory of the potentiometric methods of studying complexes of ionizable substrates was developed, nd graphical techniques are described for obtaining stability constant estimations from the data. The method described is for a system in which the conjugate acid and base forms of the substrate (S), are capable of forming 1:1 (SL) and 1:2 (SL2) complexes with the ligand (L). It was applied to complexes of alpha-cyclodextrin (cyclohexaamylose) with 10 para-substituted benzoic acid derivatives. Letting K11a and K12a be stability constants for the conjugate acid forms of the substrates, and K11b, K12b for the conjugate base forms, it was found that K12b is zero for all substrates, K12a is zero for seven of the substrates, and K11a greater than K11b in every case. Hammett plots yielded p11a and p11b values of -0.31 and 0.77, respectively, which was interpreted to mean that K11a mainly represents binding at the carboxylic acid site, and K11b describes binding at the site of the para-substituent. This model of the complexing suggests that K12a represents binding at the para-substituent, and therefore K12a should vary roughly with substituent as K11b does; this trend was observed.

Acids↗