Ab initio study of the (5R)- and (5S)-TT pyrimidine h⁵(6-4) pyrimidone photoproducts. Implications on the design of new biologically relevant analogues

Dupradeau, F., Sonnet, P., Guillaume, D., Senn, H.M. and Clivio, P. (2002) Ab initio study of the (5R)- and (5S)-TT pyrimidine h⁵(6-4) pyrimidone photoproducts. Implications on the design of new biologically relevant analogues. Journal of Organic Chemistry, 67(26), pp. 9140-9145. (doi: 10.1021/jo020604g)

Abstract

A computational study of a series of N₁- and/or C₆-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 N₁-position favors a half-chair conformation with the C₅ -and C₆-substituents in the equatorial position. On the other hand, in the case of the (6S)-1,6-dimethyl-5,6-dihydrothymine, the C₆-substituent adopts the axial position to minimize its van der Waals interactions with the N1-substituent. Furthermore, if the configuration at the C₅-dihydrothymine position has no resultant influence on the total molecular free energy, when a pyrimidone substituent is introduced at the dihydrothymine C₆-position, additional repulsive forces between the C₅- and C₆-substituents make the diaxially substituted half-chair conformation the most energetically favorable one. These results indicate that the observed C6-axially substituted conformation of the thymine-thymine pyrimidine h⁵(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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Senn, Dr Hans
• Authors: Dupradeau, F., Sonnet, P., Guillaume, D., Senn, H.M., and Clivio, P.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• Publisher: American Chemical Society
• ISSN: 0022-3263
• ISSN (Online): 1520-6904
• Published Online: 05 December 2002