ORIGINAL PAPER Conformational flexibility of pyrimidine rings of nucleic acid bases in polar environment: PCM study Oleg V. Shishkin Leonid Gorb Jerzy Leszczynski Received: 31 January 2009 / Accepted: 28 May 2009 / Published online: 17 June 2009 Ó Springer Science+Business Media, LLC 2009 Abstract The results of calculations of molecular struc- tures of nucleic acid bases in polar environment using Polarized Continuum Model of solvent combined with the MP2/cc-pvdz level of ab initio theory demonstrate con- siderable polarization of thymine, cytosine, and guanine. This phenomenon can be related to considerable contri- bution of zwitter-ionic resonant forms into total structure of the studied species. It leads to significant increase (about 30%) of frequencies of the out-of-plane pyrimidine ring vibrations and is related to considerable decrease of con- formational flexibility of heterocycle due to smaller out- of-plane deformability of pyrimidine ring in zwitter-ionic resonant forms. In the case of adenine, the presence of a polar environment results in an increase of conformational flexibility of pyrimidine ring. Keywords Nucleobases  Solution  Polarization  Conformational flexibility  MP2  PCM Introduction The conformational flexibility of DNA macromolecules plays a very important role in the structure and functioning of these biopolymers. This especially concerns relaxation of geometry of nucleic acid bases during interactions with water, proteins, intercalating agents, drugs or counterions [1, 2]. For many years ability of these biopolymers to change their conformations was associated with confor- mational flexibility of sugar-phosphate backbone while stacked and hydrogen bonded nucleic acid bases were considered to be quite rigid fragments. However, later it was demonstrated that pyrimidine ring in uracil, thymine, cytosine, and guanine possesses high conformational flexibility [3, 4]. Transition from a planar equilibrium conformation to a non-planar one characterized by values of endocyclic torsion angles up to ±20° results in energy increase \ 1.2 kcal/mol. This indicates that these mole- cules can change their conformations easily in order to maximize energy of intermolecular interactions or mini- mize any steric strain. The same conclusion was derived for pyrimidine ring in adenine also, despite its aromatic character [5]. Recent investigation of nucleic acid bases by ab initio Carr–Parinello molecular dynamics method [6] demonstrated that only a fraction of 12–30% of molecules possesses a planar geometry of ring at the every moment of time. High conformational flexibility of pyrimidine rings in nucleobases represents important source of relaxation of geometry of molecules for various inter- and intramolec- ular interactions. In particular, asymmetric distribution of water around adenine results in out-of-plane deformation of pyrimidine ring in order to maximize adenine–water interactions [7]. Similar deformations were found in some conformers of 2 0 -deoxyribonucleotides due to formation of O. V. Shishkin (&) STC ‘‘Institute for Single Crystals’’, National Academy of Science of Ukraine, 60 Lenina Ave., 61001 Kharkiv, Ukraine e-mail: shishkin@xray.isc.kharkov.com O. V. Shishkin Department of Inorganic Chemistry, V.N.Karazin Kharkiv National University, 4 Sovobody sq., 61077 Kharkiv, Ukraine L. Gorb  J. Leszczynski Interdisciplinary Nanotoxicity Center, Department of Chemistry and Biochemistry, Jackson State University, P.O. Box 17910, 1325 Lynch Street, Jackson, MS 39217, USA L. Gorb Department of Molecular Biophysics, Institute of Molecular Biology and Genetics, National Academy of Science of Ukraine, 150 Zabolotnogo str., 03143 Kyiv, Ukraine 123 Struct Chem (2009) 20:743–749 DOI 10.1007/s11224-009-9477-1