title: Ab initio study of the (5R)- and (5S)-TT pyrimidine h5(6-4) pyrimidone photoproducts. Implications on the design of new biologically relevant analogues.
abstract: A computational study of a series of N(1)- and/or C(6)-alkyl-5,6-dihydrothymine diastereomers at theory levels up to MP4(SDTQ)/6-31G//HF/6-31G and MP2/6-311G//HF/6-31G has demonstrated the respective importance of the substituents at positions 1, 5, and 6 on the energetically favored conformation of each isomer. Results obtained both in the gas and condensed phase indicate that unsubstitution of the N(1)-position favors a half-chair conformation with the C(5) -and C(6)-substituents in the equatorial position. On the other hand, in the case of the (6S)-1,6-dimethyl-5,6-dihydrothymine, the C(6)-substituent adopts the axial position to minimize its van der Waals interactions with the N(1)-substituent. Furthermore, if the configuration at the C(5)-dihydrothymine position has no resultant influence on the total molecular free energy, when a pyrimidone substituent is introduced at the dihydrothymine C(6)-position, additional repulsive forces between the C(5)- and C(6)-substituents make the diaxially substituted half-chair conformation the most energetically favorable one. These results indicate that the observed C(6)-axially substituted conformation of the thymine-thymine pyrimidine h(5)(6-4) pyrimidone photoproducts is not necessarily induced by the macrocyclic structure. They also nicely explain the formation mechanism of these photoproduct derivatives, and allow the prediction of the conformation of new analogues.
authors.affiliation: ICSN, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. fyd@u-picardie.fr
authors.forename: François-Yves
authors.initials: FY
authors.lastname: Dupradeau
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
authors.forename: Dominique
authors.initials: D
authors.lastname: Guillaume
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Senn
authors.forename: Pascale
authors.initials: P
authors.lastname: Clivio
mesh_terms: D019295:Computational Biology; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010777:Photochemistry; D011743:Pyrimidines / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D011743:Pyrimidines; D011744:Pyrimidinones