Theoretical Studies Of The Structural Properties And Reaction Mechanism Of Nonnormal DNA Bases

Deoxyribonucleic Acid (DNA) is the main material foundation of biogenetics and plays a role in the storage and transmission of genetic information. DNA possesses the self-assembled and replicated structure, which ensures the possibility for DNA to act as carrier of genetic information and provides potential for DNA-based molecular wires. During the life process, DNA molecule is prone to be modified by physical, chemical and other factors. Modification of DNA will eventually lead to DNA base structure changes, DNA-protein crosslinks and DNA strand breaks, etc., thus, a variety of nonnormal DNA bases are formed in this process. In recent years, the studies on the structures and properties of nonnormal DNA bases have evoked intense attention of experimental and theoretical chemists, and they have carried out much research on them. These nonnormal DNA bases have important applications in the fields of biological and functional materials. In the present dissertation, density functional theory and dynamics simulation have been performed to investigate the structural properties and reaction mechanisms of nonnormal DNA bases induced by oxidative and radiation damage, low-energy electron attach, and metal modification. Some interesting phenomena and valuable results have been observed in this dissertation, which can be described as follows:1. Density functional theory calculations were employed to study the stabilization process of the guanine radical cation through amino acid interactions as well as to understand the protection mechanisms. Structural and electronic properties of the interacting complexes between various amino acids and the G radical cation have been examined in this work. On the basis of our calculations, several protection mechanisms are proposed in this work subject to the type of the amino acid. Our results indicate that a series of three-electron bonds (O∴O, O∴N, O∴π, S∴N, S∴O and S∴π) can be formed between the amino acids and the guanine radical cation which may serve as relay stations supporting hole transport. These weak interactions not only contribute significantly to the stabilization of the amino acid-nucleobase dimers, but also serve as bridges for ET between the amino acid and the nucleobase in biochemical reactions. In the three-electron-bonded, π-π stacked, and H-bonded modes, amino acids can protect guanine from oxidation or radiation damage by sharing the hole, while amino acids with reducing properties can repair the guanine radical cation through proton-coupled electron transfer (PCET) or electron transfer (ET). In addition, redox amino acids with low ionization potentials (IPs) play a sacrificial role in protecting DNA against oxidative damage. Another important finding is that positively charged amino acids (ArgH+, LysH+, and HisH+) can inhibit ionization of guanine through raising its ionization potential. In this situation, a negative dissociation energy for hydrogen bonds in the hole-trapped and positively charged amino acid-Guanine dimer is observed, which explains the low hole-trapping efficiency. We hope that this work provides valuable information on how to protect DNA from oxidation-or radiation-induced damages in biological systems.2. We present here a theoretical investigation of the structural and electronic properties of the di-ionized GG base pairs (G+G+, GrG+, and GrGr) consisting of the guanine cation radical (G+) and/or dehydrogenated guanine radical (Gr) using density functional theory calculations. Different coupling modes (Watson-Crick hydrogen bonding/WC, Hoogsteen hydrogen bonding/Hoog, minor groove/min, and π-π stacking modes) are considered. We infer that a series of G+G+complexes can be formed by the high-energy radication. On the basis of density functional theory and complete active space self-consistent(CASSCF) calculations, we reveal that in the H-bonded and N-N cross-linked modes,(G+G+)Wc,(GrG+)minⅡ,(GrG+)minⅢ,(GrGr)wc (GrGr)minⅠ, and (GrGr)minⅢ have the triplet ground states,(G+G+)Hoogl,(GrG+)Wc,(GrG+)HoogI,(GrG+)minⅠ, and (GrGr)minⅡ possess open-shell broken-symmetry singlet diradical ground states, and (G+G+)HoogⅡ,(G+G+)minⅠ,(G+G+)minⅡ,(G+G+)minⅢ,(G+G+)HoHo,(GrG+)HoHo, and (GrGr)HoHo are the closed-shell systems. For these H-bonded diradical complexes, the magnetic interactions are weak, especially in the diradical G+G+series and GrGr series. The magnetic coupling interactions of the diradical systems are controlled by intermolecular interactions (H-bond, electrostatic repulsion, and radical coupling). The radical and radical interaction in π-π stacked di-ionized GG base pairs ((G+G+)ππ,(GrG+)ππ, and (GrGT)ππ) are also considered, and the magnetic coupling interactions in these π-π stacked base pairs are strong. These results offer the first theoretical prediction that some di-ionized GG base pairs possess diradical characters and these diradical base pairs show variable degrees of ferromagnetic and antiferromagnetic characteristics, depending on the binding sites and base types. Hopefully, this work provides some helpful information for the understanding of different state character of the di-ionized GG base pairs.3. We present ab initio molecular dynamics simulations (AIMD) combined with quantum chemistry calculations of structural character and evolution dynamics of electron in the (e-)aq cavity and DNA bases. Our aim is to give an overall understanding of the solvation and transport behavior of the low-energy electron ((e")aq) in solvated DNA bases. Initially, the electron survives in a cavity composed of6water molecules. The electron solvation ((e-)aq) cavity is formed by pointing their dangling hydrogens toward the trapped electron. As the evolution proceeds, the fluctuations of water and base lead to a slight reorganization of the (e-)aq... bases structure. During the AIMD simulations, there are potential wells of (e-)aq cavity and DNA bases to adjust and the electron tends to migrate to the part which has the shallow potential well. By monitoring the trajectory, we found that solvation cavity gradually splits and electron is transferred gradually to the base in the system. That is to say, in this situation, the ability of capturing electrons for DNA bases is better than that of (e-)aq. Inspection of the spin density of the snapahots in the AIMD simulation for (e-)aq...bases(G/C/A/T) reveals that, for all cases,π*-type LUMO over the bases are the sites of residence of the electron. In other words, the electron prefers to occupy the π*-type LUMO of nucleobases (G, C, A, and T) rather than produce a reorganized cavity in water. We found that within100-200fs the electron almost resides on the bases. And with about90-150fs the electron solvation cavity disappears. In addition, the water cannot reorganize itself and create a cavity to solvate the electron. These findings could be attributed to the special structures, electronic properties of the DNA bases and the nature of the (e-)aq cavity. This present work provides insight into the study of dynamics of DNA damage, which are fundamental for understanding of electron migration mechanisms in the solvated DNA bases.4. Metal-modified DNA base pairs, which possess potential electrical conductivity and can serve as conductive nanomaterials, have recently attracted much attention. We have theoretically explored the geometrical and especially the electronic properties of multi-Cu-mediated mismatched base pairs (G3GuT and A2CuC), using density functional theory calculations. The results reveal that these multi-Cu-mediated mismatched base pairs still have planar geometries and possess favorable stability because of the presence of the Cu-N/O covalent or semicovalent bonds and the Cu…Cu metallophilic interaction. It is shown that charge and structural changes mainly occur in the hydrogen-bonding zones. Orbital analysis shows that the copper atoms contribute to the occupied orbitals below HOMO in both G3CuT and A2cuC. We can draw the conclusion that the main factor affecting the gap is the electrostatic effect of copper atoms while the structural changes contribute little. It is interesting to note that their HOMO-LUMO gaps and ionization potentials decrease significantly compared to the corresponding natural base pairs(GiSoT, GTiSo, AiSoC, and ACiSo), which is expected for conductive molecular wires. To explore the transverse electronic communication between the two bases in a multi-Cu-mediated mismatched base pair, we examined their electronic absorption spectra. As evidenced by the charge transfer excitation transitions, transverse electronic communication of G3CuT and A2CuC is remarkably enhanced, suggesting that they facilitate electron migration along the DNA wires upon incorporation. Further examinations also clarify the possibility to build promising DNA helices using the G3CuT and/or A2CuC base pairs. The calculated electronic properties of the three-layer-stacked multi-Cu-mediated mismatched base pairs illustrate that the Cum-DNA have better conductivity. This work provides perspectives for the development and application of DNA nanowires.In summary, the stability of the DNA bases, structural properties, interactions, and dynamic changes of a series of nonnormal DNA bases have been examined by theoretical methods. The interesting findings are not only important for getting better understanding of the electron transfer mechanisms involved in the life processes, but also open a new strategy for their functional applications in biomedical field and biotechnology.