Interactions Of Cationic Porphyrin Derivatives With DNAs And Synthesis Of Novel Phenanthroline And Imidazole Derivatives

G-quadruplexes are found in many important genomic regions and the formationof them in vivo have an important influence up on the gene expression. To detect theaccurate conformation of G-quadruplexes is a prerequisite for the study of theirbiological functions. Therefore, a chemical probe which can specifically recognizeG-quadruplexes in the presence of duplex and single-stranded DNAs should bedeveloped. Because the cell sizes of porphyrin ring and G-quartet are close, there arepotentially biological function to exist in their interaction. Porphyrin and itsderivatives are becoming focus candidates in the study of the G-quadruplex struture.A large number of papers have been reported which keep focus on the interactionbetween monomeric G-quadruplex and small ligands under dilute conditions.However, living cells are crowded with many biomacromolecules, such as nucleicacids, polysaccharides, proteins and so on. These crowding conditions can greatlyaffect the structure and stability of G-quadruplexes. What's more, stabilization of theG-quadruplexes would be significantly reduced or even completely lose. Therefore, itis more important to study the interactions between G-quadruplexes and ligands undercrowding conditions.Based on the consideration above, a new cationic porphyrin derivative with largeside arm substituents was designed and synthesized. The feasibility of the ligand to bethe probe for the G-quadruplexes were studied under dilute and crowding conditionrespectively.The following aspects are included in this paper:1) Using combination spectroscopic (UV, fluorescence and CD) techniques, wedemonstrated that TMMPOPP, a new cationic porphyrin derivative, can also perfectlydiscriminate G-quadruplexes from duplex, single-stranded and triplex DNAs underdilute solution and molecular crowding conditions.2) The effects of four kinds of Mn(II) complexes of naphthalene-1,8-dicarboxylate ligand on cancer cell viability were firstly studied via MTT assay. Theresults indicated that the four complexes could significantly inhibit the proliferation ofhuman breast cancer cells, and the IC50values range from5.89to13.44?M.3) Three novel2-(4-hydroxyphenyl) imidazo [4,5-f]1,10-phenanthrolinederivatives were successed to be designed and synthesized.