Structures and thermodynamics of biphenyl dihydrodiol stereoisomers and their metabolites in the enzymatic degradation of arene xenobiotics

A key step in the metabolic degradation of biphenyl xenobiotics is catechol formation upon dehydrogenation of cis ‐ and trans ‐dihydrodiols in prokaryotic and eukaryotic pathways, respectively. Structure and thermodynamics of stereoisomers of cis ‐, trans ‐2,3‐biphenyl‐dihydrodiols ( I ) and their dehydrogenation products (hydroxyketones, II ), as well as final catechol (2,3‐biphenyldiol, III ) are studied by means of ab initio MP2/6‐311++G(2df,2p)//MP2/6‐311G(d,p) calculations. Formation of stereoisomers I and II is exothermic and endergonic, whereas III is enthalpically and entropically driven. Dehydrogenations are endothermic (Δ H   R 0∼ 1.5–4 kcal mol −1 ) and exergonic (Δ G   R 0∼ −5 to −7.5 kcal mol −1 ) without noticeable differences between cis and trans pathways, although the same keto stereoisomer II ‐(2S) is found to be the more favored product from both cis ‐ and trans ‐ I . The final II → III tautomerization is thermodynamically enhanced (Δ H   R 0∼ −27, Δ G   R 0∼ −28 kcal mol −1 ) but the process is shown to have a large activation energy if it had to occur via unimolecular path. Although this tautomerization is generally assumed to be a nonenzymatic process as it involves rearomatization of an oxygenated ring, proton transfer with an anionic intermediate might be a more probable process. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009