Theoretical Study On Tautomerism And Proton Transfer Of Nucleic Acid Bases

Nucleic acid bases and their thio derivatives are found in many biological systems and they are very important from the clinical point of view. The researches on the conformation and the tautomeric equilibria and proton transfer of nucleic acid bases and their thio derivatives system are the bases of understanding the constructional characters and biological function of nucleic acid. In this work, we have studied two important nucleic acid molecules: 2, 4-Dithiothymine,2-imidazolone and their thio derivatives:1. The DFT(B3LYP/6-31+G*)method was used to study the relative stabilities and probable proton transfer in isolated and monohydrated 2,4-dithiothymine molecules in gas phase. The effects of water on relative stabilities and the rate of the proton transfer were analysed. The results indicate that only one tautomer for 2, 4-dithiothymine can exits in gas phase. The interaction with one water molecule dose not change the order of relative stability and decreases the activation barriers of the proton transfer reactions for 2,4-dithiothymine.2. We have studied the relative stabilities and probable proton transfer in isolated and monohydrated 2-imidazolone and 2-thioimidazolone molecules in gas phase using ab initio(MP2/6-31+G*)method. The results show that for both molecules the keto tautomer is the relatively stable construction in isolated and monohydrated states. Monte Carlo (MC) simulation with free energy perturbation(FEP) techniques have been used to study the proton transfer reaction of two molecules system in water. The calculated free energies of activation and the relative energy of production of four proton transfer reactions are found to be lower than in gas phase and the reduction of free energies of activation of 2-thioimidazolone system is found to be most significant. All the results show that the proton transfer reaction of monohydrated 2-imidazolone and 2-thioimidazolone could occur easily in gas phase and in water and they could be observed easily experimentally.