Analysis of uracil hydration by means of vibrational spectroscopy and density functional calculations M.-P. Gaigeot, C. Kadri, M. Ghomi * Laboratoire de Physicochimie Biomole Âculaire et Cellulaire, UPRESA CNRS 7033, Case Courrier 138, Universite  Pierre et Marie Curie, 4 Place Jussieu, F-75252 Paris Cedex 05, France Received 31 August 2000; accepted 29 September 2000 Abstract Interaction of water molecules (up to seven) with uracil (RNA base) through the ®rst hydration shell has been analysed by means of density functional theory (DFT) calculations at the B3LYP/6-31G p level. Water molecules in uracil 1 2H 2 O and uracil 1 4H 2 O complexes interact with adjacent N±H and CyO chemical groups of the base. In addition to these groups, water molecules are also H-bonded to the uracil C±H groups in the uracil 1 7H 2 O complex. It has been shown that the formation of water dimer and water trimer around uracil is necessary to complete its ®rst hydration shell. Harmonic vibrational calculations have been performed after full geometry optimisation of each compound. A discussion has then been undertaken on the vibrational analysis of uracil in going from gas phase to solution state on the basis of available observed vibrational spectra and those calculated for isolated uracil and uracil 1 nH 2 O complexes. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Uracil; Nucleic acids; Hydration; DFT calculations; Vibrational spectra 1. Introduction Water is the natural medium of all biological mole- cules, participating in different processes involving the living cell. Particularly, several structural features that are necessary for the biological functions of nucleic acids, such as DNA double helix formation or RNA folding, are dependent on their interactions with surrounding water. The hydration of nucleic acids is controlled by the interaction of water mole- cules with various hydrophilic sites such as phos- phates, bases and sugars [1]. Water is a highly polar molecule which can be simultaneously an acceptor and a donor of H-bond via the interactions occurring through its oxygen or hydrogen atoms, respectively, with the nucleic acid constituents. As far as the nucleic acid bases are concerned, due to their chemical structure the majority of the H-bond interactions between them and water are of the following types: CyO´´´H, N±H´´´O and N´´´H±O. In this work, we focus our attention on uracil (RNA base) which is the structurally simplest base of nucleic acids and can mainly interact with water molecules through its H1, O2, H3 and O4 sites (Fig. 1). The main purpose of this paper is to analyse the hydrogen bonding features of uracil with up to seven water molecules. Stable con®g- urations of uracil±water complexes will be taken into consideration by means of full geometry optimisation. Calculated vibrational spectra of uracil and uracil± water complexes are also discussed on the basis of avail- able vibrational spectra observed in gas phase and aqueous solutions of uracil. Journal of Molecular Structure 565±566 (2001) 469±473 0022-2860/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0022-2860(00)00848-6 www.elsevier.nl/locate/molstruc * Corresponding author. Tel.: 133-1-44277555; fax: 133-1- 44277560. E-mail address: ghomi@lpbc.jussieu.fr (M. Ghomi).