title: ipso-substitution: a general biochemical and biodegradation mechanism to cleave alpha-quaternary alkylphenols and bisphenol A.
abstract: Sphingobium xenophagum Bayram is capable of metabolizing 4-alkoxyphenols and endocrine disruptive alpha-quaternary 4-nonylphenols by an ipso-substitution mechanism that involves ring hydroxylation at the site of the substituent. Here, we show that Bayram's ipso-hydroxylating activity was able to transform also bisphenol A (= dimethyl-4,4'-methylenediphenol; BPA) and 4-isopropylphenol. We identified six metabolites when resting cells of strain Bayram were incubated with BPA. They were unambiguously characterized by HPLC-UV, HPLC/MS, and HPLC/MS/MS as hydroquinone, 2-(4-hydroxyphenyl)isopropanol, 4-isopropenylphenol, 4-isopropylphenol, 4-hydroxy-4-isopropenylcyclohexa-2,5-dien-1-one, and 4-hydroxy-4-isopropylcyclohexa-2,5-dien-1-one. In experiments with 4-isopropylphenol as a substrate, 4-hydroxy-4-isopropylcyclohexa-2,5-dien-1-one, one of the metabolites from BPA, accumulated to a high degree. We could rationalize the formation of all metabolites by invoking ipso-hydroxylation and ipso-substitution mechanisms. On closer view, also classical bacterial metabolism of BPA can be well rationalized by an ipso-substitution mechanism, albeit with ipso-attack of an internal alkyl radical instead of an activated oxygen species. This highlights the important role of ipso-substitution as a versatile degradative principle utilized by diverse organisms to degrade alpha-quaternary 4-nonylphenols, 4-alkoxyphenols, and BPA.
authors: Swiss Federal Institute for Aquatic Science and Technology (Eawag), CH-8600 Dübendorf.
authors: Frédéric L P
authors: FL
authors: Gabriel
authors: Maike
authors: M
authors: Cyris
authors: Walter
authors: W
authors: Giger
authors: Hans-Peter E
authors: HP
authors: Kohler
mesh_terms: D001559:Benzhydryl Compounds; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D010636:Phenols / Q000378:metabolism*; D020578:Sphingomonas / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C028690:4-isopropylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds