Coupling Mechanism Related To The Life Processes Of Nucleic Acid Bases Uracil And Related Properties

Nucleic acids are the most important substantial foundation, and they play a prominent role in biological systems. Meanwhile, they are vital in descendiblity, aberrance, develop of organism and also in compound of the protein molecules. Uracil, which forms part of these compounds, has already become the hot topics of many studies because of its biological and pharmaceutical activities. A series of thiouracils have been identified as minor components of t-RNA, where some of them have been used as anticancer and antithyroid drugs. The dioxo tautomer of Uracil is the most stable in the natural status. For the isolated Uracil, the shift of the appropriate hydrogen atoms can generate many different tautomers. Moreover, theoretical studies demonstrate that some tautomers of Uracil possibly result in the mispair of nucleic acid base pairs. Thus, it is no wonder that the explorations of the influence of the outer conditions on the structures and properties of Uracil have become a prime importance area in chemistry and biology.Quantum chemistry is becoming increasingly important within the field of chemistry. Its rapid development, application, and influence are evidenced by modern chemical theories and approaches as well as the continuous increase in the sophistication of computational techniques. Investigations on the influence of different biological surroundings on the structures and properties of the Uracil should be helpful in understanding the essence of Uracil. A series of work have been carried out employing the hybrid density functional theory B3LYP/6-31+G^* , B3LYP/6-311+G^*, and B3LYP/6-311++G^** level of theory in this thesis. The primary innovations are related as follows.Firstly, the association behaviors between Uracil with Zn²⁺ in vacuum and in the presence of extra water molecules have been investigated systematically. For Uracil-Zn²⁺ complexes, the bidentate coordination mode is more stable among the possible complexes relative to the monodentate case. The interaction of Zn²⁺ with Uracil results in the shift of the appropriate hydrogen atoms. Moreover, a four-membered chelate ring has been formed in the bidentate coordination mode. In these systems, the interaction of Zn²⁺ with the carbonyl oxygen O4 is systematically favored relative to O2. The calculated Zn²⁺ bonding energies in Uracil-Zn²⁺(H₂O) complexes are reduced in comparison to those of the unhydrated Uracil-Zn²⁺ complexes. The corresponding IR spectra changes indicate that all the band intensities of C₂=O have been enhanced though the association interaction of Zn²⁺ with Uracil is weakened due to the successive hydrations of Zn²⁺ site. In the monodentate coordination complexes, the hydration effects are larger than those in the bidentate coordination complexes. The most basic center in the Uracil remains the same regardless of whether introducing the water molecules to Zn²⁺ or not. Additionally, the most acidic site of Uracil has been changed from N₁- to N₃-H group before and after introducing the Zn²⁺ and there is a significant increase in the overall acidity of the system.Secondly, the influences of thioketo substitution on the properties of uracil and its interactions with Zn²⁺ have been systematically investigated. Those properties include the structural characteristics, acidities, ionization potentials, singlet-triplet energy gaps, and the base pairing energies of SU monomers and their dimers, where SU = 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil, respectively. Computational results suggest that the H0M0-LUM0 energy gap of uracil is evidently reduced upon thioketo substitution. Thioketo substitution leads to an increase in the acidities of the N-H groups for both uracil and its dimmer. The N₁-H group is still the most acidic site relative to that of N₃-H group, implying the stronger ability to form intermolecular H-bonds for the former. However, the opposite behaviors are true for the ionization potentials and the singlet-triplet energy gaps of uracil monomer and its dimer, suggesting that thiouracils are more susceptible to radiation damage through the loss of an electron relative to the unsubstituted uracil. Additionally, for U::U and SU::SU base pairs, the influences of both ionization and excitation on the hydrogen bond involving sulfur substituent directly are more significant than those without substitution. The Zn²⁺ binding energy and the stability of U::U base pair have been increased and decreased upon thioketo substitution, respectively.In the end, the effects of methylation on the properties of uracil and adenine-uracil base pair have been investigated. Computational results suggest that the geometrical changes of uracil are not significant and the approximately planar structures are still kept upon uracil O-methylation. The acidities of uracil are enhanced whether O2- or O4-methylation, but not as significantly as introducing Zn²⁺. Moreover, the effect of 04-methylation on its acidities is larger than that of O2-methylation. For [MeA-U]⁺, the geometrical changes of adenine-uracil are also not significant and the approximately planar structures are still kept upon adenine N7-methylation, the C8-H group in adenine is the most acidic site and the C5-H group in uracil is the weakest acidic site, where the loss of a proton from adenine is comparatively easy.