Solubilization of Terfenadine,Riboflavin, and Sudan III by Aqueous Multi-basic Organic Acids

ABSTRACT

The aqueous solubility of terfenadine, riboflavin, and Sudan III (water-insoluble compounds) was enhanced by the addition of multi-basic organic acids, including citric, glutaric, malic, malonic, and tartaric acids. The variations of physical properties (density, viscosity, electrical conductivity, pH, and surface tension) against acid concentration (0–3.6 M at 25°C) were measured in order to explore possible mechanisms of solubility enhancement. Apart from the partial molar volumes, the measured physical properties varied nonlinearly with acid concentration. Glutaric acid contributes to solubility enhancement of terfenadine and Sudan III more than citric acid, with the latter slightly more effective towards riboflavin. Tartaric acid is the least effective, while malic and malonic acids occupy an intermediate position. Among the organic acids examined, only glutaric acid solutions exhibit significant surface activity, which lends itself to solubility enhancement of the three hydrophobic drugs (interfacial packing of 55 ± 3 Å² at the air–water interface, critical aggregate concentrations (CAC) at 1.8 ± 0.4 M). In contrast, all five organic acid solutions of terfenadine demonstrate more effective lowering of the surface tension of water, with the terfenadinium acid salts exhibiting interfacial packing of 108 ± 9 Å² at the air–water interface. On the other hand, organic acid solutions of riboflavin and Sudan III exhibited essentially no surface activity, aside from the intrinsic contribution of the organic acids themselves. Thus, self-association of glutaric acid contributes to the solubility enhancement of the three hydrophobic drugs. This combined with the surface activity of terfenadinium acid salts explains the higher tendency of glutaric acid to solubilize terfenadine. Mixed micellization of terfenadinium glutarate and glutaric acid occurs with an interfacial packing of 166 ± 18 Å² at the air–water interface. The corresponding CAC were estimated at 3.1 ± 0.2 mM for terfenadinium glutarate and 8.0 ± 0.4 mM for glutaric acid. Intermolecular hydrogen bonding with the extensive hydroxyl group network of riboflavin reflects the higher affinity of citric acid than glutaric acid towards riboflavin. The variability in solubility enhancement exhibited by tartaric, malic, and malonic acids appears to be a result of the interplay between several factors including intra- vs. inter-molecular hydrogen bonding, slight organic acid surface activity, and acid hydration.     

Influence of containing moisture on hydrothermal stability of modified collagen thermal characteristics analysis by DSC

The thermal stability of sheepskin collagen cross-linked with chrome sulfate and mimosa (MI)–oxazolidine (OZ), respectively, had been researched in this experiment. All samples’ shrinkage temperatures (T _s) are determined by a special T _s-testing-apparatus and denaturation temperatures (T _d) are determined by the differential scanning calorimetry. The relations between the modified collagens containing moisture and their hydrothermal stability, T _s or T _d, were studied. The results show that the cross linking agents can enhance the thermal stability of modified collagen whose T _s are 109.8 and 110.6 °C for collagen treated with chrome and MI–OZ, respectively. When the samples contain 25–71.9% moisture for chrome leather and 20–71.1% for leather treated with MI–OZ, the hydrothermal stability will decrease with the increase of moisture. It was found that the difference between T _s and T _d of collagen modified by chrome is more obvious than that of collagen modified with MI–OZ. And when the moisture of chrome leather exceeds 55%, T _d cannot express thermal stability of modified collagen as a substitute for T _s, and the moisture is 40% for leather tanned with MI–OZ.     

Electrogenerated Chemiluminescence Based on Tris(2,2′-bipyridyl) Ruthenium(II) with Hydroxyl Carboxylic Acid

Upon the electrochemical oxidation of tris(2,2′-bipyridyl) ruthenium(II) [Ru(bpy)²⁺₃] and hydroxyl carboxylic acids, for instance, citric acid, tartaric acid, malic acid, and -gluconic acid, bright electrochemiluminescences (ECLs) were observed. Different luminescent reactions were presented depending on the applied potential. The light emission was mainly caused by the reaction between alkoxide radical ion and Ru(bpy)³⁺₃below the potential +1.80 V (vs Ag/AgCl). The luminescence intensity obviously increased because of the more complex reaction process. The luminescence wavelength of 608 nm, which could be found either at higher potential than +1.80 V or in the potential range from +1.30 to +1.80 V, confirmed that ECL was caused by Ru(bpy)²⁺₃*. The factors which affect the determination and HPLC separation of the four acids were also investigated.     

Kinetics and Mechanism of the Reduction of Enneamolybdomanganate(IV) by Citric Acid

The kinetics and mechanism of reduction of enneamolybdomanganate(IV) by citric acid in acidic solution was studied by spectrophotometry, and showed that the reaction, with respect to enneamolybdomanganate(IV) and to citric acid, is pseudo-second-order and first-order, respectively. The values of 1/k_obs increase with the values of [H⁺] and reaction rates increase with temperature. The activation parameters of the rate-determining steps were evaluated. A mechanism related to this reaction is proposed.     

The structures of low molecular weight glycerin propoxylates: An experimental,semi-empirical,and Monte Carlo study

A simple Monte Carlo model has been developed for calculating the structural features and properties of low molecular weight triols produced by the base-catalyzed propoxylation of glycerin. The model computes the probability of a reaction to a specific oligomer from the local site reactivities of model compounds with an adjustment for the molecular weight of the reacting oligomer. The resulting product array is then used to calculate typical polymer properties such as average molecular weight, polydispersity, and average chain length. Trial rate constants were estimated from the activation energies of MNDO-PM3 semi-empirical molecular orbital theory. For the compounds used to model the oligomer chain end groups, the activation enthalpies were found to be within the ranges reported for experimental values. Although the predicted enthalpies of activation were significantly higher for the alkoxylation directly at glycerin, this was found to be attributable to intramolecular hydrogen bonding in the reactants that was disrupted in the transition states. Although the hydrogen bonding energies were higher than what are normally considered typical, comparison tests showed that the calculated energies agreed well with experimental values of alkoxide anion–alcohol systems. The PM3 rate constants, when used to calculate Monte Carlo probabilities, predicted the isomer distribution of the four isomeric monopropoxylates with a error of 4%. Optimization of the model reduced this to 0.5%. However, to accurately predict the oligomer distribution of higher molecular weight adducts and other properties, the correction term (M₀/M_i)^b had to be included, where M₀/M_i is the ratio of the molecular weight of glycerin to the molecular weight of the oligomer undergoing alkoxylation, and b is assigned the value 0.7. Although b is empirical, it is consistent with a simple molecular mechanics (MM2) conformational study of the relative availability of the reactive end groups. When the final model was used to simulate the propoxylation of glycerin for a variety of PO/glycerin ratios, it was found to accurately reproduce properties such as primary hydroxyl content, polydispersity, oligomer distribution, and change in the monopropoxylate isomer ratio as a function of bulk PO/glycerin ratio. © 1995 John Wiley & Sons, Inc.     

Interaction of Maleic Acid Copolymers with Collagen

One of the present trends to increase the efficiency of the chrome tanning process is the use of chemicals which change the affinity and induce a better binding of the chromium ions in the hides. Recently, some anionic polyelectrolytes based on poly(acrylic acid) or maleic acid copolymers were developed as additives in the chrome tanning. The effect of polyelectrolytes could be explained by their interaction with the collagen from hide. In our work four maleic acid copolymer/collagen systems were investigated by turbidimetric, conductometric and potentiometric titrations. The interaction between the two macromolecular compounds was clearly evidenced, and its dependence on the chemical structure of the maleic acid copolymer and on the amount of added chromium ions was studied. Homogeneous systems or turbid dispersions were observed depending on the hydrophilic or hydrophobic character of the maleic copolymer, on the [CH]/[MP] ratio, and on the concentration of the chromium ions.     

Polymerization of trimethylene carbonate in aqueous solutions: Reaction mechanism and characterization

Polymerization of a trimethylene carbonate (TMC) in an aqueous solution was investigated by gel permeation chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance. The polymerization reaction proceeded rapidly in the aqueous solution and high conversion was achieved in a relatively short time. 1,3‐Propanediol (PPD) formed by hydrolysis of TMC was used as the initiator. The TMC oligomer obtained by ring‐opening polymerization had a TMC unit backbone with terminal 3‐hydroxypropyl groups at both chain ends. The oligomer underwent transesterification reaction with elimination of PPD, resulting in a gradual increase in the molecular weight of the product. The molecular weight was affected by the concentration of TMC. The thermal properties of the polymers were investigated by differential scanning calorimetry. Polymers within the molecular weight (M_n) range from 6.0 × 10³ to 2.3 × 10⁴ g/mol crystallized, and endothermic peaks corresponding to the melting temperature were observed. The glass transition temperature increased with the molecular weight of the polymers. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1485–1492, 2010     

Kinetic Study of the Bromine-Catalyzed Isomerization of Methyl- and Chloro-Maleic Acids in Aqueous Ce(IV)-Br -H2SO4 Medium

Methylmaleic (citraconic, CTA) acid and methylfumaric (measaconic, MSA) acid in aqueous sulfuric acid solution undergo bromine-catalyzed reversible cis-trans isomerization in the presence of ceric and bromide ions. The positional isomerization of CTA or MSA to itaconic acid (ITA) is not observed. The method of high performance liquid chromatography (HPLC) was applied to study the kinetics of this catalyzed isomerization. The major catalytic species is best expressed as the Br^?₂ · radical anion. Under suitable catalytic conditions, there is a tendency for the [MSA]/[CTA] ratio to reach an equilibrium value of 4.10 at 25° for the CTA+Br^?₂ · ? MSA+Br^?₂ · reaction. Chloromaleic (CMA) and chlorofumaric (CFA) acids undergo similar isomerization with an equilibrium [CFA]/[CMA] ratio of 10.3 at 25°. The isomerization of maleic acid (MA) to fumaric acid (FA) is essentially irreversible with 50 as the lower limit of the equilibrium [FA]/[MA] ratio. The substituent has an important effect on the reversibility of this catalyzed isomerization of butenedicarboxylic acids. The thermodynamic parameters ΔH° and ΔS° at 25° for the CTA+Br^?₂ · ? MSA+Br^?₂ · reaction were found to be ?5.1±0.7 kj/mol and ?6.0±3.3 J/mol K, respectively. The present method gives a plausible way to measure the differences in enthalpy and entropy between the trans- and cis-isomers of butenedicarboxylic acids (CRCO₂H=CR'CO₂H) in aqueous solution.     

Further relaxation kinetic investigations of iron(III) chelation. Data for diglycolic,tartaric, and citric acids

The kinetics of the reactions of iron(III) with diglycolic, tartaric, and citric acids have been studied in aqueous acid solutions by the temperature-jump method at 25.0°C and at ionic strengths 1.0 (for tartaric and citric acids) and 0.50 mol/dm³ (for diglycolic acid). The experimental data indicate that iron(III) monochelate formation occurs by the same reaction mechanism for all three ligands examined and that only pathways involving the FeOH²⁺ ion contribute to the chelation process. The reacting species for citric acid is the undissociated ligand. For tartaric and diglycolic acids both the neutral ligands and the corresponding monoanions react significantly under the experimental conditions used. Kinetic evidence for the contribution of intermediate steps to the limiting rate in the overall chelate-formation process has been obtained and discussed.     

RADIATION INDUCED ACRYLAMIDE/CITRIC ACID HYDROGELS AND THEIR SWELLING BEHAVIORS

Citric acid (CAc) moieties containing acrylamide (AAm) hydrogels were prepared by gamma irradiation of their aqueous solutions. A possible polymerization and crosslinking mechanism for acrylamide/citric acid (AAm/CAc) hydrogels is proposed. The effects of irradiation dose and citric acid content on swelling behavior were investigated. Swelling took place in water at 25°C and was followed gravimetrically. Incorporation of a relatively low amount of citric acid to acrylamide hydrogel increased its swelling up to 950% from 700%. The diffusion of water into AAm/CAc hydrogels was found to be a non-Fickian type. Diffusion coefficients of AAm/CAc hydrogels found as 5 × 10^?7? 10 × 10^?7 cm² sec^?1. It has also been found that the number average molar mass between crosslinks is increased with the CAc content and decreased with irradiation dose.     

Effect of acid on morphology of calcite during acid enhanced defluoridation

Fluoride removal from water by lime materials is a promising defluoridation process. Acid enhanced limestone defluoridation (AELD) technique involves precipitation of CaF₂ as well as adsorption of fluoride on the surface of limestone which is capable of reducing fluoride concentration to below the WHO guideline value of 1.5 mg/L. Acids such as acetic acid and citric acid are added to the fluoride water before filtration through limestone column to enhance the Ca²⁺ activity in solution for precipitation of fluoride as CaF₂. This paper describes the effects of these acids on the quality of the limestone during the AELD process, which has been studied to evaluate the reusability of the limestone. The reaction products that formed during the AELD process have also been analyzed. The detail study of the morphology of the limestone before and after use have been done using various analytical techniques, viz., X-ray diffraction, infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy combined with energy dispersive X-ray spectroscopy. The study reveals that the limestone degrades to some extent in the process due to dissolution of calcium carbonate by the acids and adsorption of fluoride by the limestone. While appreciable quantity of the citrate salt of calcium was formed in the column, the acetate salt mostly remained dissolved in the water. Since mainly the surface of the limestone particles take part in the reaction, the limestone particles can be reused for the defluoridation process after cleaning the outer surface. The limestone after use remains also suitable as raw material for cement.     

A study of the kinetics of the microwave cure of a phenylethynyl‐terminated imide model compound and imide oligomer (PETI‐5)

The kinetic mechanism of the microwave cure of a simple phenylethynyl‐terminated imide model compound, 3,4′‐bis[(4‐phenylethynyl)phthalimido]diphenyl ether (PEPA‐3,4′‐ODA) and a phenylethynyl‐terminated imide oligomer (PETI‐5, M_n 5000 g/mol) was studied. Dielectric properties of the model compound and PETI‐5 were measured in the microwave range from 0.4 GHz to 3 GHz. FTIR was used to follow the cure of the model compound (PEPA‐3,4′‐ODA), while thermal analysis (DSC) was used to follow the cure of the PETI‐5 oligomer. The changes in room temperature IR absorbance of phenylethynyl triple bonds at 2214 cm⁻¹ of PEPA‐3,4′‐ODA as a function of cure time were measured after cure temperatures of 300, 310, 320, and 330 °C. The changes in the glass‐transition temperature, T_g, of PETI‐5 as a function of cure time were measured after cure at 350, 360, 370, and 380 °C, respectively. The T_g 's were determined to calculated the relative extent of cure, x, of the PETI‐5 oligomer according to the DiBenedetto equation. For the model compound, the reaction followed first order kinetics, yielding an activation energy of 27.6 kcal/mol as determined by infrared spectroscopy. For PETI‐5, the reaction followed 1.5th order, yielding an activation energy of 17.1 kcal/mol for the whole cure reaction, as determined by T_g using the DiBenedetto method. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2526–2535, 2000     

THE EQUILIBRIA AND KINETICS OF THE COMPLEX FORMATION BETWEEN Fe(III) AND TARTARIC AND CITRIC ACIDS

Abstract

The equilibria and kinetics of formation of 1 : 1 iron(III) complexes with tartaric and citric acids have been studied in the pH range 1.0–2.0 in aqueous alcoholic perchlorate media. The equilibrium constants for the reactions Fe³⁺ +

H₄L^keq Complex + nH⁺ were obtained from spectrophotometric measurements in the wavelength range 360–420 nm. The values of K _eq determined at 20°, μ=1.0 M (water 100%), were 0.21 M with n=2 for tartaric and 0.0186 M² with n=3 for citric acid. The stoichiometry of the complex formation and the reaction sites of the ligands were discussed with reference to previous findings on ligands of related structures. The kinetics of the reactions were carried out by the stopped-flow technique. From the hydrogen ion dependence of the reaction rates it can be shown that complex formation occurs between FeOH²⁺ and differently protonated forms of the ligands. Forward rates for the different paths are consistent with an SN1 IP interaction in agreement with the Eigen mechanism; forward and reverse rate quotients enabled the evaluation of the equilibrium constants which agreed satisfactorily with the spectrophotometric ones. The effect of varying the solvent composition (water-alcohol) was discussed with reference to the reaction mechanism.     

Quantitative analysis of malic and citric acids in fruit juices using proton nuclear magnetic resonance spectroscopy

¹H NMR spectroscopy was applied to the quantitative determination of malic and citric acids in apple, apricot, pear, kiwi, orange, strawberry and pineapple juices. Aspartic acid was studied as a potential interference. The effect of the sample pH on the chemical shifts of signals from malic, citric and aspartic acids was examined and a value of 1.0 was selected to carry out the determination. Integration of NMR signals at 2.89-2.95 and 3.00-3.04 ppm were used for calculating the concentration of malic and citric acids, respectively. At this pH the integrated signals were not overlapped. Sodium 3-(trimethylsilyl)tetradeuteropropionate (TSP) was used as an internal reference. The obtained results applying NMR procedures to analyze the juices from different fruits were compared to those obtained using enzymatic methods and both were in close agreement. The intra- and inter-day repeatability was tested for apple juice (7.86 g l⁻¹ malic acid, 0.32 g l⁻¹ citric acid) and apricot juice (5.06 g l⁻¹ malic acid, 4.79 g l⁻¹ citric acid) obtaining coefficients of variation lower than 3.4% for intra-day measures (n = 10) and lower than 3.8% for inter-day measures (n = 20).     

Simultaneous dual wavelength spectrophotometric determination of citric and ascorbic acids using an artificial neural network

In this study, a very simple spectrophotometric method for the simultaneous determination of citric and ascorbic acid based on the reaction of these acids with a copper(II)-ammonia complex is presented. The Cu²⁺-NH₃ complex (with λ_max = 600 nm) was decomposed by citrate ion and formed a Cu²⁺-citrate complex (with λ_max = 740 nm). On the other hand, during the reaction of ascorbic acid with copper(II)-ammonia complex, ascorbic acid is oxidized and the copper(II)-ammonia complex is reduced to the copper(I)-ammonia complex and the absorbance decreases to 600 nm. Although there is a spectral overlap between the absorbance spectra of complexes Cu²⁺-NH₃ and Cu²⁺-citrate, they have been simultaneously determined using an artificial neural network (ANN). The absorbances at 600 and 740 nm were used as the input layer. The ANN architectures were different for citric and ascorbic acid. The output of the citric acid ANN architecture was used as an input node for the ascorbic acid ANN architecture. This modification improves the capability of the ascorbic acid ANN model for the prediction of ascorbic acid concentrations. The dynamic ranges for citric and ascorbic acid were 1.0–125.0 and 1.0–35.0 mM, respectively. Finally, the proposed method was successfully applied to the determination of citric and ascorbic acids in vitamin C tablets and some powdered drink mixes. The text was submitted by the authors in English.     

Synthesis of poly(glycolic acid) in ionic liquids

The synthesis of poly(glycolic acid) (PGA) by polyesterification of glycolic acid was studied using ionic liquids, mainly 1,3‐dialkylimidazolium salts, as reaction media. The ¹H NMR spectra of PGA oligomers were assigned and end‐group signals were used to follow the reaction. Low PGA yields were obtained by the direct polyesterification of glycolic acid at 200–240 °C, because of monomer evaporation during the reaction. On the other hand, PGAs of DP _n up to 45 were obtained by the postpolycondensation of a preformed oligomer in 1‐butyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)amide (BMIm⁺Tf₂N^?). The precipitation of PGA in reaction medium at long reaction times limited the achievable molar mass. Rate constants were determined for catalyzed and noncatalyzed reactions, assuming a second‐order reaction mechanism. The efficiency of esterification catalysts such as Zn(OAc)₂ was low in these media, as only about twofold increases in reaction rate were observed. This was assigned to the preferential interaction of Zn²⁺ with ionic liquid anion instead of the polymer carboxylic acid end‐groups. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3025–3035, 2006     

Gas chromatographic determination of isocitric and malic acid in the presence of a large excess of citric acid

Derivatization yields of different esters (methyl, ethyl, n-propyl, isopropyl, n-butyl and isobutyl) of citric, malic and isocitric acids with various acylating agents, such as acetic anhydride, propionic anhydride, trifluoroacetic anhydride and heptafluorobutyric anhydride, were investigated. The formation of acylated malic and isocitric acid esters is rapid and quantitative whereas the acylation of citric acid esters was slow and partial in most instances. It was found that selective analytical conditions can be achieved with the O-heptafluorobutyryl n-butyl esters. The analytical applicability of the separation and determination of the malic, isocitric and citric acid contents of model solutions and of pressed lemon juice is discussed. Concentrations of 1.2 × 10^?3 ?9.0 × 10^?3g per 100 g of isocitric acid and 4.2 × 10^?3 ?3.5 × 10^?2 g per 100 g of malic acid in the presence of 9.3 × 10^?1 g per 100 g of citric acid were measured with relative standard deviations of 7.5 and 4.2%, respectively.     

Ferrocytochrome c and deoxyhemoglobin in the reaction with the iron cysteamine nitrosyl complex {Fe2[S(CH2)2NH3]2(NO)4}SO4·2.5H2O

By an example of the iron cysteamine nitrosyl complex {Fe₂[S(CH₂)₂NH₃]₂(NO)₄}SO₄··2.5H₂O (CAC), it was shown for the first time that the hydrolysis of this NO donor in the presence of ferrocytochrome c (cyt c ²⁺) affords the iron nitrosyl complex NO-cyt c ²⁺, which serves as the NO depot. The rate constant of NO release from CAC was determined from the kinetics of the formation of NO-cyt c ²⁺. At pH 3.0 the rate constant is (2.7±0.1)·10⁻³ s⁻¹. Ferrocytochrome c produces a less stabilizing effect on CAC than deoxyhemoglobin (Hb). Thus in the presence of cyt c ²⁺, the reaction is completed in 1 h, whereas NO is released from a solution of CAC (2·10⁻⁴ mol L⁻¹) in the presence of Hb during 40 h. The previously unknown stabilization of iron nitrosyl complexes by hemoglobin was found.     

A Study of the Reaction of Phosphorus Trichloride with Paraformaldehyde in the Presence of Carboxylic Acids

Abstract

We investigated the mechanism of the reaction of paraformaldehyde with phosphorus trichloride in the presence of carboxylic acids (acetic, propanoic, and formic). Our results revealed that bisphosphonic acids were obtained without the use of water. The structures of the reaction products were studied by 1D and 2D homonuclear and heteronuclear ¹H-, ¹³C-, ³¹P- NMR spectroscopy.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional tables.]