Thiol-group reactivity, hydrophilicity and stability of alloxan, its reduction products and its N-methyl derivatives and a comparison with ninhydrin.
The diabetogenic agent, alloxan, is a hydrophilic and chemically unstable compound. The logarithm of the octanol/water partition coefficient of alloxan was found to be -1.86; its half-life at pH 7.4 and 37 degrees in phosphate buffer was 1.5 min. The partition coefficients and half-lives of the alloxan reduction products, alloxantin and dialuric acid, were very similar to those of the parent compound; N-methylalloxan and N,N'-dimethylalloxan were less hydrophilic but more unstable. Ninhydrin was found also to be hydrophilic although this compound, in contrast to alloxan and its derivatives, was quite stable in aqueous solution. Alloxan and its N-methyl derivatives were reduced by thiols and in the presence of glutathione and cysteine, rapid redox cycling occurred, with formation of 'active oxygen' species; no such reaction was observed, however, with ninhydrin. Comparatively slow redox cycling was recorded with alloxan derivatives and dithiothreitol although rapid cycling occurred with ninhydrin and this dithiol. Such differences may explain why ninhydrin does not share with alloxan a selective toxic effect upon the pancreatic B-cell.
Lenzen
S
S
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
Munday
R
R
D000496:Alloxan / Q000031:analogs & derivatives / Q000737:chemistry*; D001463:Barbiturates / Q000737:chemistry; D002021:Buffers; D009555:Ninhydrin / Q000737:chemistry*; D010084:Oxidation-Reduction; D012995:Solubility; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001463:Barbiturates; D002021:Buffers; D013438:Sulfhydryl Compounds; D000496:Alloxan; D009555:Ninhydrin; C004469:alloxantin