Rejnek Jaroslav, Hanus Michal, Kabelác Martin, Ryjácek Filip, Hobza Pavel
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems, 166 10 Prague 6, Czech Republic.
Phys Chem Chem Phys. 2005 May 7;7(9):2006-17. doi: 10.1039/b501499a.
Altogether 13 keto and enol tautomers of uracil and 13 keto and enol tautomers of thymine were studied theoretically in the gas phase, in a microhydrated environment (1 and 2 water molecules) and in a water environment. Bulk water was described using the thermodynamic integration method, Conductor-like polarizable continuum model (C-PCM, COSMO) and hybrid model (C-PCM + 1-2 explicit water molecules). The structures of various tautomers were determined at the RI-MP2 level using the TZVPP basis set while relative energies were determined at the CCSD(T) level. The relative free energies at 298 K were based on the relative energies mentioned above and zero-point vibration energies, and temperature dependent enthalpy terms and entropies evaluated at the MP2/6-31G** level. The effect of bulk solvent on the relative stability of uracil and thymine tautomers was studied using molecular dynamics free energy calculations by means of the thermodynamic integration method and self-consistent reaction field. Despite the completely different nature of these methods they provide comparable solvation free energies. Besides theoretical investigation, experimental detection of uracil and thymine tautomers was performed by means of steady-state fluorescence. We conclude that it is impossible to utilize the method used by Suwaiyan and Morsy (M. A. Morsy, A. M. Al-Somali and A. Suwaiyan, J. Phys. Chem. B, 1999, 103(50), 11205) for tautomer detection, even if a very sensitive fluorimeter is used. Theoretical relative energies and free energies for isolated uracil and thymine tautomers support the existence of the canonical form only. The microhydrated environment and bulk solvent stabilize enol forms more than the canonical keto one, but gas phase destabilization of these enol forms is too high. Population of rare enol forms of uracil and thymine in bulk water will thus be very low and canonical structure will also be dominant in this phase.
在气相、微水合环境（1个和2个水分子）以及水环境中，对尿嘧啶的13种酮式和烯醇式互变异构体以及胸腺嘧啶的13种酮式和烯醇式互变异构体进行了理论研究。使用热力学积分方法、类导体极化连续介质模型（C-PCM，COSMO）和混合模型（C-PCM + 1 - 2个显式水分子）来描述大量水。使用TZVPP基组在RI-MP2水平确定各种互变异构体的结构，而在CCSD(T)水平确定相对能量。298 K时的相对自由能基于上述相对能量以及零点振动能，并且在MP2/6 - 31G**水平评估温度相关的焓项和熵。通过热力学积分方法和自洽反应场，利用分子动力学自由能计算研究了大量溶剂对尿嘧啶和胸腺嘧啶互变异构体相对稳定性的影响。尽管这些方法的性质完全不同，但它们提供了可比的溶剂化自由能。除了理论研究之外，还通过稳态荧光对尿嘧啶和胸腺嘧啶互变异构体进行了实验检测。我们得出结论，即使使用非常灵敏的荧光计，也不可能利用苏瓦扬和莫尔西（M. A. 莫尔西、A. M. 阿尔 - 索马里和A. 苏瓦扬，《物理化学杂志B》，1999年，103(50)，11205）所使用的方法进行互变异构体检测。孤立的尿嘧啶和胸腺嘧啶互变异构体的理论相对能量和自由能仅支持标准形式的存在。微水合环境和大量溶剂使烯醇式比标准酮式更稳定，但这些烯醇式在气相中的去稳定化程度过高。因此，尿嘧啶和胸腺嘧啶在大量水中的稀有烯醇式的丰度将非常低，并且标准结构在该相中也将占主导地位。
