Molecular Modeling On Recognition Of Normal And Sheared DNA By Complex Composed Of Extended Aromatic Heterocyclic Ligands And Transition Metal

Most of the inheritance mechanism is based on the specifically recognition of nucleic acid. Thus, design of artificial synthesized small molecules which can bind and react at specific sequences of DNA been one of the focus of chemistry, biology and pharmacology. Recognition of secondary structure of DNA by trandition metal complex containing extended aromatic heterocyclic ligand has been applied widely in development of novel drug and basic biological research.However, though many metal complexes had been proved potent to be used as DNA structure probe, the mechanism of the binding and interactions have been debated. Of them, the group leaded respectively by Barton and Norden proposed the two different mechanisms. To elucidate the interaction of the complex and DNA helix, we have managed to develop some novel models based on molecular modeling. And then, investigate the detailed process of the interaction by molecule mechanics and moleculay dynamics. The sense of the work is that, the research can be performed on atom level, but not system level, so as to analyze the interaction in detailed. Moreover, considering the easiness of the molecular modeling and the computation capability, we can study more systems by molecular modeling than by experiment and then to summarize the rule during the interaction.Based on previous research on the recognition of normal DNA sequence by [Co(phen)2dppz] 3+, this thesis is focused on the recognition of normal and mismatch B-DNA sequence by [Ru(phen)2 dppz]n+, [Co(phen)2tpphz]n+, [Co(phen)2hpip]n+ and [Rh(bpy)2Chrysi]3+. During the work, we successfully modeled the experiment results of other international workgroups. On addition, by study the potential energy change during the interaction, we analyze the detailed process of all systems and make some elucidation on the experiment results.By molecular modeling, we study the disputation on the recognition mechanism in detailed.Then we bring forward our viewpoints, and the elucidate the possible factors leading to the disputation.The thesis is composed of following works:1. Modeling modeling on the recognition of B-DNA sequence [d(GTCGATCGAC)2] by , -[Co(phen)2tpphz]3+. Because the intercalating ligand tpphz is more conjugatedthan the ligand dppz, [Co(phen)2tpphz]3+ can be used as an electron acceptor of DNA tranfer systems. Calculating results indicate that, only when the complex intercalating into DNA helix from minor groove by head-on or side-on style, the intercalation can be finished successfully. Furthermore, the recognition should be enantioselective, and the A -[Ru(phen)2 dppz]3+ is preferable to the other one.2. Molecular modeling of normal and sheared B-DNA sequence by A , -[Ru(phen)2dppz]n+. By comparison on the recognition of normal and sheared DNA sequence, it can be foundthat, the intercalation at the mismatch site of sheared DNA sequence more specificially than into normal sequence. Calculating results indicated that: (1) the recognition is site specificially. The mismatch site is more preferable; (2) the recognition is enantioselective, and the - [Co(phen)2dppz]n+ should be more competitive than the other. The steric and staticelectro interaction is the main factors leading to the enantioselectivity. But, the energy difference between the the intercalation by the two isomers is not so distinct that it is possible that the enantioselectivity not be observed by experiment methods. This maybe the factors cause the different viewpoints of different international workgroups; (3)distinct groove selectivity is observed. Intercalation from minor groove is preferable, the main cause leading to the results can be staticelectro interaction; (4) after intercalation, the distance between the two base pairs at the intercalating site doubled.3. Molecular modeling of normal and sheared B-DNA sequence by A , -[Co(phen)2hpip]n+. Calculation on the recognition of the homologous sequences by the novel complex suggests that, the complex can intercalating specific...