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Structures and thermodynamics of biphenyl dihydrodiol stereoisomers and their metabolites in the enzymatic degradation of arene xenobiotics
Author(s) -
Pacios Luis F.,
Campos Víctor M.,
Merino Irene,
Gómez Luis
Publication year - 2009
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21248
Subject(s) - chemistry , exergonic reaction , tautomer , dehydrogenation , biphenyl , endothermic process , computational chemistry , stereochemistry , catechol , organic chemistry , catalysis , adsorption
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