Conformational ¯exibility of pyrimidine ring in adenine and related compounds Oleg V. Shishkin a,b, * , Leonid Gorb b , Jerzy Leszczynski b a Department of Alkali Halide Crystals, Institute for Single Crystals, National Academy of Sciences of Ukraine, 60 Lenina ave., 61072 Kharkiv, Ukraine b Computational Center for Molecular Structure and Interactions, Department of Chemistry, Jackson State University, P.O. Box 17910, 1325 Lynch Street, Jackson, MS 39217, USA Received 20 June 2000; in ®nal form 15 September 2000 Abstract The structural non-rigidity of aromatic pyrimidine rings in adenine and selected related compounds has been in- vestigated by quantum chemical non-empirical methods of calculation at the MP2 and DFT levels of theory. The results of the calculations demonstrate that the pyrimidine ring possesses a notable degree of conformational ¯exibility despite its aromatic character. The transition of the heterocycle from a planar equilibrium geometry to a non-planar structure with an endocyclic torsion angle of 20° results in an energy increase of less than 2.8 kcal/mol. An analysis of the population of ground and excited vibrational levels for the lowest out-of-plane vibration of the ring indicates that in adenine 45% of the molecules have a non-planar pyrimidine ring with relevant torsion angle up to 17° at any moment of time. Ó 2000 Elsevier Science B.V. All rights reserved. 1. Introduction For many years, nucleic acid bases were expected to be planar and conformationally rigid [1,2]. How- ever, it was recently demonstrated that the pyrimidine ring in uracil, thymine, cytosine, isocytosine, and guanine possesses high conformational ¯exibility [3,4]. The transition of the heterocycle in uracil from a planar equilibrium to a sofa conformation with an N(1)±C(2)±N(3)±C(4) torsion angle of 20° results in an energy increase of less than 1 kcal/mol. High deformability of the pyrimidine ring is also retained in Watson±Crick adenine±thymine and guanine±cytosine base pairs [5] and stacked dimers of thymine, cy- tosine, and thiocytosine [6]. An analysis of the molecular structure and conformational ¯exibility of nu- cleobase analogues has led to the conclusion that this property of the pyrimidine ring is caused by a deviation of the character of the cyclic p-system from aromatic [4,7±9]. It is well known [10] that the high conformational ¯exibility of the molecule is associated with the presence of one or several vibrational modes with frequencies below 200 cm 1 . An analysis of the theo- retical and experimental vibrational data for nucleobases [11] con®rms this conclusion. Recently, [12], we 17 November 2000 Chemical Physics Letters 330 (2000) 603±611 www.elsevier.nl/locate/cplett * Corresponding author. Fax: +380-572-321082. E-mail address: shishkin@xray.isc.kharkov.com (O.V. Shishkin). 0009-2614/00/$ - see front matter Ó 2000 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 2 6 1 4 ( 0 0 ) 0 1 1 2 7 - 1