Adelbert M. Knevel

Direct current and differential pulse polarography of penicillamine

Abstract The direct current and differential pulse polarographic behavior of the sulfhydryl group of penicillamine in 0.056 M citrate buffer of pH 6.45 was investigated. Depending on the concentration of penicillamine, one, two, or three waves were obtained. In most of the concentration regions investigated (1×10−5–1×10−3 M), a linear relationship was found to exist between concentration and the d.c. wave height. In the case of d.p. polarography, a linear relationship was obtained below the 5×10−4 M level. A study of the effects of mercury pressure on d.c. wave heights, the effects of Triton X-100 on both d.c. and d.p. polarograms, and the analysis of electrocapillary curves indicates that penicillamine exhibits an adsorption wave. Log plot analysis indicates that the electrode reaction product is RSHg. The calculated d.p. peak current was found to be lower than the experimental current, and the diffusion coefficient of penicillamine in 0.056 M citrate buffer of pH 6.45 was found to be 7.8×10−6 cm2 s−1.

A kinetic analysis of the acidic degradation of penicillin G and confirmation of penicillamine as a degradation product

Two recently proposed degradation pathways for the acidic degradation of pencillin G were examined by calculating the theoretical time course based on each pathway and examining the fit of the theoretical predictions to the experimental data. A substantial difference in the goodness of fit was observed. The degradation pathway which provided the best fit included penicillamine as a terminal degradation product. This pathway is therefore favoured since penicillamine was also identified as a degradation product of penicillin G by both reversed-phase high pressure liquid chromatography and differential pulse polarography.

An alternating current polarographic determination of nonprotein sulfhydryl in biological systems

Abstract A sensitive alternating current polarographic method of determination of NPSH in biological systems is described. Ascorbic acid does not interfere with the determination. The method can detect the physiological differences in nonprotein sulfhydryl levels in rat liver caused by stress.

Investigation of a proposed penicillin G acidic degradation scheme using high-pressure liquid chromatography and optimization techniques and mechanistic considerations

Optimization techniques were used to fit a recently proposed degradation scheme to recently published n.m.r. data for the time course of penicillin G and four degradation products at pH 2.5 and 37°C. Several conclusions arising from the n.m.r. analysis which were originally associated with the degradation scheme were not compatible with the optimized rate constants. It was necessary to change substantially the proportion of penicillin G degrading through benzylpenicillenic acid, benzylpenillic acid, and benzyl-penicilloic acid in order for the degradation scheme to fit the n.m.r. data. Benzylpenillic acid replaced benzylpenicillenic acid as the major product. The rate constants best describing the n.m.r. data showed benzylpenicillenic acid proceeding almost exclusively through benzylpenamaldic acid. Such optimization implied that the scheme could be simplified to three parallel reaction pathways, the dominant reaction occurring through benzylpenillic acid. However, mechanistic considerations indicate that the direct conversion of penicillin G into benzylpenillic acid is not possible and that a likely intermediate is benzyl-penicilloic acid. The degradation of benzylpenicilloic acid at pH 2.5 was consequently monitored by ionpair reversed-phase high-pressure liquid chromatography and rapid formation of benzylpenillic acid was detected. This observation is inconsistent with the recently proposed degradation scheme, even though the scheme can be made to fit the n.m.r. kinetic data.

Comparative studies of temporal changes in polarographic currents and ultraviolet absorption of benzylpenicillenic acid

Abstract The time behavior of the polarographic current and u.v. absorbance of benzylpenicillenic acid in buffers at different pH values are compared. The rate of decrease of current with time is the same as the rate of decrease of absorbance in the intermediate pH region but is slower in the alkaline and acidic regions. The slower rate in these regions is explained by the transformation of the thiazolidinyl-oxazolone isomer to the u.v.-absorbing and polarographically active isomer at the electrode.

Molecular inclusion complexation of tolbutamide with permethyl-β-cyclodextrin

The formation of a stable inclusion complex between tolbutamide and permethyl-β cyclodextrin was systematically studied. It shows that permethyl-β-CD forms a 1 : 1 complex with tolbutamide. Its molecular structure was elucidated by physicochemical methods including IR and high field NMR analysis. The influence of pennethyl-β-cyclodextrin on the hypoglycemic effect of tolbutamide was evaluated by measuring the blood glucose level. The reduction in plasma glucose was significantly greater when the rabbits were treated with the complex than with tolbutamide alone. The enhancement of the bioavailability of tolbutamide by permethyl-β-cyclodextrin is likely attributed to the molecular inclusion effect.