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J. Phys. Chem. B 2006, 110, 26388-26395
Dimerization and Double Proton Transfer-Induced Tautomerism of 4(3H)-Pyrimidinone in Solution Studied by IR Spectroscopy and Quantum Chemical Calculations Adchara Padermshoke,† Yukiteru Katsumoto,§ and Misako Aida*,†,§ Center for Quantum Life Sciences, Hiroshima UniVersity, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan, Department of Chemistry, Graduate School of Science, Hiroshima UniVersity, Higashi-Hiroshima, Hiroshima 739-8526, Japan ReceiVed: August 22, 2006; In Final Form: October 26, 2006
The tautomerism and dimerization of 4(3H)-pyrimidinone (4(3H)Pyr) in carbon tetrachloride (CCl4) and chloroform (CHCl3) solutions were investigated using IR spectroscopy and quantum chemical calculations. The observed IR spectra in the NH and OH stretching regions clearly revealed the predominance of the keto tautomer in both solvent systems. The enol form only exists in a very small proportion in the CCl4 solution. The tautomeric constant for the two monomers KT[OH/NH] ) 0.012 and ∆E ) 2.62 kcal/mol were estimated at 25 °C. This result was supported by the self-consistent reaction field/polarizable continuum (SCRF/PCM) calculation at the MP4(full, SDQ)/aug-cc-pVDZ level, which predicted ∆E ) 3.06 kcal/mol in CCl4. In the CdO stretching region, two bands were observed, suggesting the coexistence of two keto structures at equilibrium. The calculated IR spectra indicated that the bands at 1711 and 1675 cm-1 arise from the keto monomer and keto-keto (KK) ring dimer, respectively. At elevated temperature, the populations of both the keto and enol monomers increased for the CCl4 solution. The present study revealed that the keto T enol tautomerization does not occur in the isolated monomer molecule. The double proton transfer (DPT) reaction in the KK ring dimer presumably plays a substantial role in the population increase of the enol monomer. To our knowledge, this may be the first observation of the tautomerization in a model base pair via the temperatureinduced ground-state DPT reaction under a nonpolar liquid environment reported so far. This tautomerism can serve as a mimic circumstance for the spontaneous mutations induced by proton transfer in the DNA base pairs.
Introduction The tautomerism of purine and pyrimidine nucleobases is of keen interest because it directly affects the biological functions and properties of nucleic acids. The fidelity of DNA replication and transcription as well as the stabilization of secondary and tertiary structures of the nucleic acids are governed by the specific hydrogen bonds between proper tautomeric forms of the complementary bases.1,2 The presence of rare tautomers can result in DNA mismatches, which lead to spontaneous and induced mutageneses.1,3-5 Recently, the tautomerism and structure of the nucleobases6-17 and their analogues18-28 have been studied extensively by various theoretical and experimental approaches. IR spectroscopy is one of the most powerful techniques frequently used for investigating such properties of the nucleobases and related compounds. Changes in the tautomeric equilibrium, molecular structure, and hydrogen-bonding state of the bases are clearly revealed by the variations in IR spectral features.18,20,22 4(3H)-Pyrimidinone (4(3H)Pyr) (Figure 1) has often been considered as a suitable model compound for studying the prototropic tautomerism of the nucleobases. 4(3H)Pyr exhibits a structure similar to that of the pyrimidine ring of the bases while presenting relatively small possibilities of specific interactions, thus facilitating the study of the more complex systems. * Author to whom correspondence should be addressed. E-mail: maida@ hiroshima-u.ac.jp. Tel.: +81-82-424-5735. Fax: +81-82-424-5736. † Center for Quantum Life Sciences. § Department of Chemistry, Graduate School of Science.
Figure 1. Three tautomeric forms: keto, enol, and keto (N1H), of 4(3H)Pyr.
Moreover, its keto and enol forms, respectively, resemble the six-membered parts of the “normal” amino-oxo and “mutagenic” amino-hydroxy forms of guanine,2,3 one of the most widely studied DNA components. The knowledge of the tautomerism and structure of 4(3H)Pyr, therefore, is of considerable importance and can be very useful for gaining insight into the actual nucleobase systems. The previous studies suggested that 4(3H)Pyr exists in comparable amounts of the keto and enol forms in the gas phase and low-temperature matrixes.18,19 In the condensed phase, on the other hand, the keto form predominates.18,20 The conversion of the keto form to the enol one can be observed in inert gas matrixes after UV irradiation.19,20 A number of the combined experimental and theoretical studies have also been performed for 4(3H)Pyr19,24 and similar compounds8,26-28 to predict their tautomeric stabilities and establish the vibrational assignments.
10.1021/jp065408i CCC: $33.50 © 2006 American Chemical Society Published on Web 12/08/2006
Dimerization and Tautomerism of 4(3H)-Pyrimidinone However, the detailed information regarding the tautomerism and structure of 4(3H)Pyr in the solution phase is somewhat limited due in part to its poor solubility in less polar solvents. In other words, most studies are particularly relevant to the gas phase or matrix-isolated conditions where intermolecular interactions are suppressed. These interactions, as a matter of fact, play a crucial role in the physicochemical properties of the physiologically existing nucleobases. In the present study, we have investigated the tautomerism and structure of 4(3H)Pyr in the liquid solvent media: carbon tetrachloride (CCl4) and chloroform (CHCl3) solutions, using IR spectroscopy. Effects of the temperature and concentration of the solutions on the observed IR spectra were also monitored. Quantum chemical calculations were employed to assist the interpretation of the experimental spectra and predict the relative stabilities of the 4(3H)Pyr species. The weakly interacting nature and yet relatively simple IR absorptions of CCl4 and CHCl3 allow the accurate comparison of the experimental and theoretical spectra. Besides, their hydrophobic character is of relevance to the environment prevailing in the interior of a DNA helical structure. Methodology Experiment. 4(3H)Pyr (98+%) was purchased from TCI (Japan) and used as received. Spectral grade CCl4 and CHCl3 were obtained from Wako (Japan) and dried over molecular sieves until used. All IR measurements were performed using a Nicolet 6700 FT-IR spectrometer equipped with a mercury cadmium telluride (MCT) detector at a spectral resolution of 1 cm-1. To ensure a high signal-to-noise (S/N) ratio, 256 scans were co-added. The sample cells employed for the measurements were KBr, CaF2, and SiO2 transmission liquid cells with the path lengths of 1 mm, 5 mm, and 5 cm, respectively. 4(3H)Pyr/CCl4 and 4(3H)Pyr/CHCl3 solutions were prepared in concentration ranges of 0.01-0.5 and 0.2-10 mM, respectively. Concentration-dependent IR spectra of the freshly prepared samples were then recorded at room temperature. Temperature-dependent IR spectra were collected for the 4(3H)Pyr/CCl4 solution (
