Acid-catalyzed Hydrolysis Reactions Research Articles

Temperature and pH dependence of fluocinolone acetonide degradation in a topical cream formulation.

We investigated the degradation of fluocinolone acetonide (FA) incorporated into an oil-in-water cream base. The study examined the influence of temperature (23 to 80 degrees C) and cream pH (pH 2.3 to 6) on FA degradation rates. FA degradation followed pseudo-first-order kinetics and adhered to the Arrhenius expression over the entire temperature range investigated. At all temperatures, the pH strongly influenced the observed degradation rate constant (kobs) values, with rate minima observed near pH 4. The FA log(degradation rate)-pH profiles were consistent with a reaction mechanism requiring drug hydrolysis catalyzed by hydroxide and hydrogen ions. Taking into account both the temperature and the pH dependence of FA degradation permits calculating kobs values from the following equation: kobs = exp[22.5 - (17,200/RT)] + exp[38.7 - (22,200/RT)] x [H+] + exp[49.5 - (21,100/RT)] x [OH-] where the three bracketed terms represent Arrhenius expressions for neutral, acid-catalyzed, and base-catalyzed hydrolysis reactions. FA degradation in the cream base parallels the degradation of a related steroid (triamcinolone acetonide) in an aqueous alcohol solution. The equivalence between FA and triamcinolone acetonide kinetics in the different reaction media suggests that in the cream base, FA degradation is limited to an aqueous phase largely unperturbed by the presence of nonaqueous constituents that comprise the cream formulation.

Gas chromatography study of the acid catalyzed hydrolysis of tetraethylorthosilicate [Si(OC 2H 5) 4

The acid catalyzed hydrolysis reaction of tetraethylorthosilicate [TEOS] was monitored using gas chromatography. In these experiments TEOS was hydrolyzed using molar ratios of H 2O:TEOS of 1:1 and 4:1 at temperatures of 21, 45, and 65°C. In all cases the pH of the solution was between 0.5 and 1. The extent of hydrolysis was indirectly measured by monitoring the volume percentage of ethanol generated. It was found that for all of the conditions studied the amount of ethanol generated reached a peak within 20–25 min after initiation of the reaction and then remained constant with time. Our results indicate that for the conditions studied, the 4:1 ratio led to roughly 77% of full hydrolysis and the 1:1 ratio led to roughly 20%.

Oxygen-18 isotope effect in carbon-13 nuclear magnetic resonance spectroscopy. 9. Hydrolysis of benzyl phosphate by phosphatase enzymes and in acidic aqueous solutions

The /sup 18/O isotope-induced shifts in /sup 13/C and /sup 31/P nuclear magnetic resonance (NMR) spectroscopy were used to establish the position of bond cleavage in the phosphatase-catalyzed and acid-catalyzed hydrolysis reactions of benzyl phosphate. The application of the /sup 18/O-isotope effect in NMR spectroscopy affords a continuous, nondestructive assay method for following the kinetics and position of bond cleavage in the hydrolytic process. The technique provides advantages over most discontinuous methods in which the reaction components must be isolated and converted to volatile derivatives prior to analysis. In the present study, (..cap alpha..-/sup 13/C,ester-/sup 18/O)benzyl phosphate and (ester-/sup 18/O)benzyl phosphate were synthesized for use in enzymatic and nonenzymatic studies. Hydrolysis reactions catalyzed by the alkaline phosphatase from E. coli and by the acid phosphatases isolated from human prostate and human liver were all accompanied by cleavage of the substrate phosphorus-oxygen bond consistent with previously postulated mechanisms involving covalent phosphoenzyme intermediates. An extensive study of the acid-catalyzed hydrolysis of benzyl phosphate at 75/sup 0/C revealed that the site of bond cleavage is dependent on pH. At pH less than or equal to 1.3, the hydrolysis proceeds with C-O bond cleavage; at 1.3 < pH < 2.0, there is a mixturemore » of C-O and P-O bond scission, the latter progressively predominating as the pH is raised; at pH greater than or equal to 2.0, the hydrolysis proceeds with exclusive P-O bond scission. (S)-(+)-(..cap alpha..-/sup 2/H)Benzyl phosphate was also synthesized. Hydrolysis of this chiral benzyl derivative demonstrated that the acid-catalyzed C-O bond scission of benzyl phosphate proceeds by an A-1 (S/sub N/1) mechanism with 70% racemization and 30% inversion at carbon. 37 references, 4 figures, 2 tables.« less

A New Chemical Method for Measurement of Mean Temperatures with Special Applicability to Cold Environments

A method for the measurement of mean integrated temperature using a spectrophotometer to trace the course of a chemical reaction is described. The substrate, phenyl ,8-D glucopyranoside, has an acid catalysed hydrolysis reaction with a temperature response similar to that of biological processes. The accuracy of the technique (? 0.50C) is similar to the sucrose inversion method. Advantages of the new technique are 1) use of a spectrophotometer which is more commonly available than a polarimeter, 2) ability to measure in temperatures as low as -40'C and 3) storage of samples in an inactive state. Arrhenius parameters are given but it is recommended that these be calculated for each solution used. The temperature estimate is discussed in relation to environmental variability.

Kinetics of hydrolysis of polyoxyethylene (20) sorbitan fatty acid ester surfactants.

Abstract The kinetics of the hydrolysis of the oleate ester of polyoxyethylene (20) sorbitan (Tween 80) in aqueous buffers were studied at an initial concentration of 0&amp;#x006d;̇020% (w/v) and over the pH range of 1&amp;#x006d;̇10 to 10&amp;#x006d;̇28. The hydrolysis appears to be specific acid-catalysed at pH values below 3 and specific base-catalysed at pH values greater than 7&amp;#x006d;̇6. The pseudo first-order rate constants for hydrogen and hydroxyl ion catalysis were determined, and the temperature and ionic strength dependence of the acid-catalysed reaction was studied. Both the initial, acid- and base-catalysed hydrolysis of Tween 80 exhibited an unusual initial, micellar surfactant concentration-rate dependence, opposite to that previously reported for the hydrolysis of anionic surfactants of the n-alkyl sulphate-type. Specifically, as the initial concentration of Tween 80 was increased above its reported critical micellar concentration, there was a progressive, marked decrease in the rate of the reaction, with the rate eventually reaching a plateau value between 0&amp;#x006d;̇100 and 1&amp;#x006d;̇00% (w/v). It is suggested that this behaviour is due to alterations in the micellar state of the surfactant as its concentration is increased. The influence of the chemical structure of the Tween surfactant on the acid-catalysed hydrolysis reaction at 80° was also examined using the oléate (Tween 80), stéarate (Tween 60), and palmitate (Tween 40) esters of polyoxyethylene (20) sorbitan.