The influence of conformational factors on the metabolic conjugation of aryloxyacetates

Abstract

Among p-chlorophenoxyalkanoic acids, the acetate and 2-propionate are essentially inert towards metabolic conjugation, whereas the isobutyrate (clofibric acid) undergoes extensive glucuronidation, as well as amino acid conjugation in carnivores. To try to explain these differences, the conformational behaviour of three model compounds was studied by quantum mechanical calculations (PCILO method). All three compounds prefer syn (folded) conformers, but the isobutyrate, in contrast to its two lower homologues, also has anti (extended) conformers of relatively low energy. Based on these results, a hypothetical topographical model is proposed for the binding site of glucuronyltransferase.

Effects of Charge and Intramolecular Structure on the Lipophilicity of Nitrophenols

“…The strong stabilization of this intramolecular hydrogen bond in nonpolar environments, already described for the partitioning of ortho-nitrophenols in alkane/water systems, renders these compounds much more lipophilic than other nitrophenols in the 1,2-DCE/water system, confirming previous experiments and ab initio MO calculations . In the octanol/water system, the large amount of water existing in the organic phase offers additional possibility of intermolecular hydrogen-bond interactions to the phenolic group.…”

The effects of the selective κ-opioid agonist MR 2034 on the guinea-pig ileum

“…Brisbane, Queensland 4000. AustraliaThe crystal structure of three aryloxyacetates have torsion angles significantly different from those forecast by van deWaterbeemd et al (1986) using quantum mechanical PCILO calculations. However, these torsion angles are near a minimum in their published three dimensional conformational maps.…”