Study Of Interaction Of Ruthenium (Ⅱ) Polypyridyl Complexes With G-quadruplex DNA

The aims of this paper are the design and synthesis of Ru(II) polypyridine complexes, as well as the study of interaction between complexes and telomeric G-quadruplex DNA/bcl2 G-quadruplex DNA. This thesis consists of four chapters.In chapter 1, The structures and characters of nucleic acid and G-quadruplex DNA, and the study methods and instance of interaction with Ru(II) complexes were presented briefly. Moreover, the relations of telomeric sequence, G-quadruplex DNA, bcl-2 and tumor inhibition were discussed as emphases. The history, development and studies of current stage of Ruthenium antitumor complexes with imidazole ligands were summarized systemically. The significance for studying on the interaction of Ru(II) polypyridine complexes with G-quadruplex was shown.In chapter 2, [Ru(bpy)2(tip)]2+(1) and [Ru(phen)2(tip)]2+(2) were synthesized and characterized. The telomeric G-quadruplex binding properties of these complexes have been investigated with UV-Vis, emission spectra, CD spectra and NMR spectra. The experimental results were given below:(1) There was great interaction between Ru(II) complexes and telomeric G-quadruplex, and the order of the binding affinity (A) is A(1)< A(2). (2) Complex 1 can induce AG3[T2AG3]3 to form the antiparallel G-quadruplex DNA, while complex 2 induces AG3[T2AG3]3 to form the mixed parallel/antiparallel G-quadruplex. (3) Complex 2 binds close to the 3' terminal face of the G-quadruplex DNA.In chapter 3, The bcl2 G-quadruplex DNA binding properties of complexes have been study by UV-Vis, emission spectra, CD spectra. The results showed that:(1) complex 1 and 2 can induce bcl-2 to form G-quadruplex, and the order of the binding affinity (A) is A(1)< A(2).(2) Complex 1 and 2 can stabilize bcl2 G-quadruplex DNA, and the order of stability is 1< 2. (3) The binding of complex 2 to bcl2 G-quadruplex DNA in Tris/NaCl buffer is greater than that of complex 1 in Tris/KCl buffer.In chapter 4, new chiral Ru(II) complexes were synthesized and characterized. The telomeric G-quadruplex DNA binding properties of these complexes have been investigated with UV-Vis,emission spectra.The result indicated that:(1)The order of the binding affinity(A)is A(A-2)>A(△-2)>A(∧-1)>A(△-1).(2)Chiral Ru(Ⅱ)complexes can stabilize telomeric G-quadruplex DNA,and the order of△Tm is△Tm(A-2)>△Tm (△-2)>△Tm(∧-1)>△Tm(△-1).(3)The enantiomer of the complex displays somewhat chiral matching.