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 (DeltaHR0 approximately 1.5-4 kcal mol(-1)) and exergonic (DeltaGR0 approximately -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 (DeltaHR0 approximately -27, DeltaGR0 approximately -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.
Unidad de Química y Bioquímica, Departamento de Biotecnología, E. T. S. Ingenieros de Montes, Universidad Politécnica de Madrid, 28040 Madrid, Spain. luis.fpacios@upm.es
Luis F
LF
Pacios
Víctor M
VM
Campos
Irene
I
Merino
Luis
L
Gómez
D015082:2,2'-Dipyridyl / Q000737:chemistry* / Q000378:metabolism; D047250:Calixarenes / Q000737:chemistry / Q000378:metabolism*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry; D003198:Computer Simulation; D049308:Dioxygenases / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism*
D002396:Catechols; D009281:Naphthalenes; D015262:Xenobiotics; C507866:trans-1,2-dihydro-1,2-naphthalenediol; D047250:Calixarenes; D015082:2,2'-Dipyridyl; D049308:Dioxygenases; C034221:catechol