Valerate Esters Research Articles

Influence of chain length on the in vitro hydrolysis of model ester prodrugs by ocular esterases.

In designing ester prodrugs to improve corneal drug bioavailability, it is important to consider the influence of chain length on both corneal permeation and hydrolysis of the prodrug. However, the second factor has received relatively little attention. The purpose of this study was to evaluate whether the ocular hydrolysis of a homologous series of alpha- and beta-naphthyl esters was influenced by chain length. Solutions of each ester were incubated with selected ocular tissues and fluids of adult albino rabbits. For the alpha-series peak hydrolytic rate was reached at the caproate (C6) ester, coinciding with minimization in the value of the Michaelis-Menten constant (Km) and maximization in the value of maximum velocity (Vmax). For the beta-series peak hydrolytic rate was reached at the valerate (C5) ester. In contrast to the alpha-series this was primarily due to a large increase in value for Km. These findings indicate that the rate of ocular esterase-mediated hydrolysis varies within a homologous series of esters, and that this chain length dependency is influenced by the chemical nature of the parent compound.

Physical Model Evaluation of Topical Prodrug Delivery—simultaneous Transport and Biocnversion of Vidarabine-5′-valerate II: Parameter Determinations

Results of initial studies on methods for determining various model parameters are reported. By employing excised hairless mouse skin in a diffusion cell system, numerous model parameter values were deduced. The stratum corneum permeability was estimated from steady-state fluxes with preparations of heat-separated epidermal membranes. Determinations of dermis diffusivities and enzyme rate constants in situ involved considering the simultaneous transport and the enzyme processes and factoring the diffusivities and enzyme rate constants from the overall kinetics. Dermal diffusivities were on the order of 10−6 cm2/sec for vidarabine and its 5′-valerate ester. The enzyme rate constants were 1.70 × 10−3 sec−1 for the esterase and 8.68 × 10−3 sec−1 for the deaminase.

Effect of molecular architecture of long chain fatty acids on the dispersion properties of titanium dioxide in non-aqueous liquids

The effect of varying chain length and chain branching on the adsorbed layer thickness of oligoesters on titania in non-aqueous solvents has been studied and related to the degree of flocculation of the dispersions using viscometry.The oligoesters were a series of monodisperse condensates of 12-hydroxystearic acid, up to the pentamer. Also, a series of branched esters in which the degree of branching was varied systematically was studied. The latter consisted of the valeric esters of mono-, di- and tri-hydroxystearic acid.It was found that the thickness of the adsorbed layer was not necessarily the criterion for good dispersion stability, but a complex function of surface concentration. This was dependent on main chain length, the size, position and number of branches and the solvency of the medium.

Nonspecific esterases of human peripheral nerve and centrum ovale. A comparison and observations on esteratic activity of myelin fractions.

Nonspecific esterases (NsE) of human PNS and CNS occur in free (hydrosoluble) and bound (triton X-100 extractible) forms. Free and bound NsE were studied in whole tissue and in myelin fractions by starch gel electrophoresis (zymograms) and chemical assay, using as substrates alpha-naphthyl acetate, (NA), alpha-naphthyl propionate (NP) and alpha-naphthyl butyrate (NB). By chemical assay whole homogenates of CNS and PNS differ thusly: (1) NP/NA and NB/NA hydrolysis ratios are greater in PNS; (2) NsE activity, whether expressed per gram wet weight or specific activity, is several-fold greater in CNS; (3) 76–86% of NsE activity of PNS occurs in free form while CNS free esterase constitutes less than 20% of the total. NA zymograms of free NsE of PNS and CNS are alike, and differ from other tissues and contain predominantly E-600-resistant A-type esterase, with a minor C-type component. Certain molecular forms of NsE preferentially hydrolyzing NP and NB (and the valerate ester) are characteristic of cerebral and cerebellar white matter and are absent from PNS, liver, kidney, skeletal muscle and leptomeninges. CNS myelin fractions, prepared as described in this publication, contain NsE of predominately B-type (E-600-sensitive enzyme). Respectively, 6.7, 8.0 and 9.1% of the NA-, NP- and NB-hydrolyzing capacity of centrum ovale are recovered in the myelin fraction. PNS myelin lacks NsE. These results, though suggestive, do not prove an intrinsic association of NsE with human CNS myelin. Autolysis, among other factors, may cause displacement of enzyme from in vivo sites. Nonetheless results reported here and in earlier papers support a role for NsE in myelin metabolism, especially of those CNS NsE that cleave preferentially 3–5 carbon esters.

Determination of the Ester Composition of Neopentyl Polyol Ester Lubricants

Because of the increasing use of the neopentyl polyol esters as lubricants, an analytical method capable of giving detailed information concerning the composition of these complex ester mixtures is desirable. Methods of gas-liquid chromatography and thin-layer chromatography have been applied in the successful development if such an analytical method. By direct programmed temperature gas chromatography of the lubricants, the components are separated according to volatility; in most cases resolution is adequate for semi-quantitative analysis. Gas-liquid chromatographic analysis of the free acids produced by hydrolysis of the sample reveals the acyl composition. The parent polyols are determined by programmed temperature gas chromatography of their valerate esters. A semi-preparative thin-layer chromatographic method permits the isolation of the three main ester types, trimethylol propane, pentaerythritol, and dipentaerythritol, for further analysis. A combination of these analytical methods permits a detailed study of the changes in composition which occur in these lubricants during service.

Solubilities of testosterone propionate in non-polar solvents at 100°

Abstract THE solubilities of the formate to valerate esters of testosterone in non-polar solvents at 25° were determined by James & Roberts (1968) who also compared them with ideal mole fraction solubilities (X2), calculated from the equation, (Hildebrand & Scott 1962). ΔHF is the heat of fusion of the solute and TM the melting point. Changes in solubility as the homologous series is ascended were predicted by equation (1), but the individual experimental results did not agree with the calculated values. ΔHF was calculated from the heat of fusion at the melting point, ΔHFM, by correcting for the differences in heat capacity of the solid and the supercooled liquid between TM and T. The correction was estimated with a differential scanning calorimeter by extrapolating the liquid enthalpy line back to 25° and measuring the area between the extrapolation and the enthalpy line of the solid. The method was considered questionable, however, because it assumed that the enthalpy line of the supercooled liquid decreased linearly over the whole range of temperature. This theory is tested below by comparing the measured and calculated solubilities of testosterone propionate at a temperature just below its melting point, where the heat capacity correction is small and ΔHFM can be used for ΔHF. The solvents examined by James & Roberts (1968) had smaller molar volumes than the testosterone esters, and it was suggested that the difference in molar volume between solute and solvent could prevent the random distribution assumed by regular solution theory. Prediction of solubility would thus improve as the molar volume of the solvent approached that of the solute. The test is applied below by determining the solubility of testosterone propionate in a range of solvents.

The solubilities of the lower testosterone esters.

Abstract The solubilities of the formate to valerate esters of testosterone have been determined in water and several organic solvents. The aqueous solubilities decrease logarithmically as the homologous series is ascended, but the acetate is less soluble than anticipated in the organic solvents. The variation in solubility from ester to ester can be predicted in the organic solvents from thermodynamic data, and is a reflection of the differences in melting point. The melting point differences are explained from the space group dimensions and the area of α to α face contact in the crystals.