The electronic effects of benzoic acid substituents on glycine conjugation.
The electronic properties of 3- and 4-substituted benzoic acids were determined by the Pariser-Parr-Pople (PPP) molecular orbital (MO) method and were then related to glycine conjugation using the mitochondria fraction of rat liver. With the exception of nitro- and cyano-substituted compounds, the conjugation activity increased linearly with the decrease in the energy (Elumo) of the lowest unoccupied molecular orbital (LUMO) and the energy (Ehomo) of the highest occupied molecular orbital (HOMO). The differences shown by the nitro- and cyano-substituted compounds have related to the low values of the atomic orbital coefficient (Cl,e) of the carboxyl carbon of LUMO and the negativity of the net charge on the substituent atom. These parameters are discussed in terms of the reactivity of the carboxyl carbon and the interaction between the compounds and enzymes. Regression analysis of the combination of these electronic parameters showed that there was a significant correlation. As far as the effect of the alkyl substituent was concerned, steric hindrance effect was noted in the case of methoxy and dimethylamino groups.
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Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd., Ibaraki, Japan.
D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D002458:Cell Fractionation; D002855:Chromatography, Thin Layer; D005998:Glycine / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar
D001565:Benzoates; D005998:Glycine