Degradation Pathway of Bisphenol A: Does ipso Substitution Apply to Phenols Containing a Quaternary α-Carbon Structure in the para Position?

Abstract

The degradation of bisphenol A and nonylphenol involves the unusual rearrangement of stable carboncarbon bonds. Some nonylphenol isomers and bisphenol A possess a quaternary ␣-carbon atom as a common structural feature. The degradation of nonylphenol in Sphingomonas sp. strain TTNP3 occurs via a type II ipso substitution with the presence of a quaternary ␣-carbon as a prerequisite. We report here a new degradation pathway of bisphenol A. Consequent to the hydroxylation at position C-4, according to a type II ipso substitution mechanism, the C-C bond between the phenolic moiety and the isopropyl group of bisphenol A is broken. Besides the formation of hydroquinone and 4-(2-hydroxypropan-2-yl)phenol as the main metabolites, further compounds resulting from molecular rearrangements consistent with a carbocationic intermediate were identified. Assays with resting cells or cell extracts of Sphingomonas sp. strain TTNP3 under an 18 O 2 atmosphere were performed. One atom of 18 O 2 was present in hydroquinone, resulting from the monooxygenation of bisphenol A and nonylphenol. The monooxygenase activity was dependent on both NADPH and flavin adenine dinucleotide. Various cytochrome P450 inhibitors had identical inhibition effects on the conversion of both xenobiotics. Using a mutant of Sphingomonas sp. strain TTNP3, which is defective for growth on nonylphenol, we demonstrated that the reaction is catalyzed by the same enzymatic system. In conclusion, the degradation of bisphenol A and nonylphenol is initiated by the same monooxygenase, which may also lead to ipso substitution in other xenobiotics containing phenol with a quaternary ␣-carbon.

Bacteria-mediated bisphenol A degradation

“…strain MV1 proposed by Lobos et al (1992) and Spivack et al (1994) but in a pathway similar to that in Sphingomonas sp. strain TTNP3 proposed by Kolvenbach et al (2007), with minor difference. 4-(2-Propanol)-phenol and HQ were the products of cleavage of the ring of BPA.…”

“…strain TTNP3 was isolated from activated sludge sample obtained from laboratory-scale semi-continuous activated sludge unit, which was fed with nonylphenol for a period of approximately 4 months (Tanghe et al 1999). However, its BPA degradation ability was firstly proposed by Kolvenbach et al (2007). Sphingomonas sp.…”

“…strain TTNP3 was to introduce one atom of molecular oxygen into the BPA by the NADPH and FAD-aided monooxygenase to form a quinol intermediate (compound III). Then, the breakage of C-C bond between the phenolic moiety and the isopropyl group of BPA occurred (Kolvenbach et al 2007). …”

“…1 The proposed BPA degradation pathways in Sphingomonas sp. strains MV1, AO1 and TTNP3 and the unidentified strain WH1 yl]cyclohex-2-ene-1,4-diol (compound XII) or 1-[2-(4-hydroxyphenyl)propan-2-yl]cyclohex-2-ene-1,4-diol (compound XIII), by a NIH shift with subsequent hydrogenations of the hydroxylated ring or direct successive hydrogenations of the ring of the quinol intermediate (Kolvenbach et al 2007). …”

Unusual Cytochrome P450 Enzymes and Reactions

“…Other examples in which cleavage of a substrate occurs in such a mechanism involve the ipso cleavage of bisphenol A (supplemental Fig. S3) (31) and the conversion of nabumetone to 6-methoxy-2-naphthylacetic acid by the human P450 CYP1A2 (supplemental Fig. S4) (32, 33).…”