| There are two parts in this thesis. In the first part, we described our works on the molecular modeling of the interactions between [Co(phen)2hpip]3+and normal/sheared DNA; in the second part, we studied the kinetic conversion between the isomers of C2Al4using the ab initio molecular dynamic simulations.For the first part, our works are based on our previous theoretical studies in our group. We studied the interactions between the metal complex [M(phen)2L]3+and normal and sheared G:A DNA to acquire the knowledge of the sheared G:A DNA repair process. The studies in this thesis focused on a Co(Ⅲ) complex with two phen ligands and a hpip ligand. Since hpip has two possible structures and previously our group had studied one of them in detail, the work in this thesis will focus on the other structure. In this part, we have following novel findings:1.[Co(phen)2hpip]3+can recognize both normal and sheared DNA. The recognition process show obvious site-specificity, isomer-selectivity, and the groove-selectivity. For the normal sequence DNA, the recognition also shows the enantiomer-selectivity. The interactions between complex and normal DNA prefer the complex with structure I of hpip, which tend to insert DNA base pair from the minor groove, while that between complex and sheared DNA prefer the complex with structure Ⅱ of hpip, which tend to intercalate DNA from the major groove. The detailed analysis suggest that the interactions between the complex and normal DNA will enrich the Delta-isomer with structure I of hpip, while that between the complex and sheared DNA will enrich the isomers with structure Ⅱ of hpip and the two enantiomers of this isomer will have a ratio of1:1.2. The interaction between the complex and sheared DNA can repair the sheared DNA from conformational aspect:the intercalation of hpip ligand into DNA base pairs adjacent to the G:A mismatched pairs will convert the intercross structure to the parallel structure.3. The detailed analysis suggest that the recognition processes were determined by the steric interaction, which the repair processes for sheared DNA were related to the tightness and integrity of π-π stacking between base pair and between the base pairs and hpip ligands.4. If we compare the work in this thesis and in our previous studies, we can conclude that the modeling in the aqueous solution is closer to the real system than that in the vacuum.For the second part, we use the ab initio Born-Oppenheimer molecular dynamic (BOMD) simulation technique to systematically study kinetic conversion process between three lowest isomers of C2Al4at the temperatures of323K and373K. We have the following novel findings.1. Our BOMD simulations suggested that the lowest isomer of C2Al4not only has best thermodynamic stability, but also possesses the very excellent kinetic stability.2. The second-and third-lowest isomers of C2Al4will convert to the lowest isomer via the isomerization reaction, which pass through a similar intermediate structure. Such structure will rapidly convert to the lowest structure in three of these four set of simulations once they are formed, however, for the simulation of the third lowest isomer at323K, such structure exists for about9.1ps, which help us to identify the intermediate structure.3. After the structural conversion, the magnitude of the fluctuation of the RMSD and potential energy curves becomes tempestuous. The reason can be attributed to the release of potential energy during the conversion, which increase the vibrational energy of molecules and thus influence the concerned curves. |
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