ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In this study, we compared the lipophilicity of O-glucuronides and their aglycones. Distribution coefficients (log D) and P values of neutral species (log P) were determined by centrifugal partition chromatography (CPC) in octanol/buffer systems. Two-phase potentiometry was also used to measure the log P value of some lipophilic solutes. The experimentally determined global influence of glucuronidation on lipophilicity, obtained as the difference (decrement) log P(glucuronide) - log P(aglycone), was found to be -1.30 ± 0.16 (n = 4) for glucuronides of alcohols (methyl, menthyl, neomenthyl, and chloramphenicol O-glucuronide). The mean decrement was -2.06 ± 0.31 (n = 9) for glucuronides of phenols (phenyl, p-nitrophenyl, 1-naphthyl, 6-bromo-2-naphthyl, 4-methylumbelliferyl, 3-coumarinyl, phenolphthalein, 4′-benzophenonyl O-glucuronide, and diflunisal phenolic glucuronide). For the acylglucuronide of diflunisal and its rearrangement isomers, the mean decrement was -1.80 ± 0.08 (n = 4; range -1.7 to -1.9). Differences in through-bond proximity effects as parametrized in the CLOGP algorithm seem to account for much of this difference. Conformational factors may also play a role, although it appears modest and unassessable for the glucuronides investigated here. The results imply that in vivo glucuronidation should have a stronger influence on the excretion of phenols than on that of alcohols.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19980810214
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