Interactions Of Ruthenium Complexes With G-quadruplex DNA And Yeast RNA

Polypyridine ruthenium（Ⅱ）complexes have attracted extensively attentions in bioinorganic chemistry due to their outstanding photochemical and physical properties,thermodynamic stability,biological activities and DNA binding properties,as well as their easily constructed structures.This thesis is concerned about the interactions of three polypyridine ruthenium（Ⅱ）complexes with G-quadruplex DNA and yeast RNA.The thesis includes the followings:1.A hydroxyquinoline-appended ruthenium（Ⅱ）complex 1 and a oxadiazole-based ruthenium（Ⅱ）complex 2 have been synthesized and characterized by ¹H NMR,¹³C NMR,FAB-MS and IR.2.The interactions of complex 1 with telomere HTG21 DNA,and complex 2 and 3 with oncogene Pu27 DNA have been investigated by UV-vis and fluorescence spectroscopy,fluorescent intercalator displacement（FID）titrations,circular dichroism（CD）spectroscopy,polymerase chain reaction（PCR）stop assay,color reaction studies,fluorescence resonance energy transfer（FRET）melting assay,Job plot and molecular modeling.The results indicated that:（1）Complex 1 could well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA,and showed superior G-quadruplex stability and selectivity over duplex DNA with remarkableΔT_m value of 21.0℃ even at 50-fold excessive supplies of calf thymus（ct）DNA;The complex bond to G-quadruplex DNA strongly in an "end-pasting"model with high affinity of 2.56×10⁶ M^-11 and 1:1[quadruplex]/[complex]binding mode ratio.The complex exhibited evident luminescence enhancements of 3.1 and 4.2-times for quadruplex binding in Na⁺and K⁺buffer,respectively.（2）Complex 2 could induce Pu27 DNA to form quadruplex structure,and displayed superior G-quadruplex stabilization ability and selectivity;In the presence of 100-fold ct-DNA or not,theΔT_m value of Pu27 G-quadruplex DNA was9.5℃;The complex bond to Pu27 G-quadruplex DNA via groove mode with binding constant of 6.6×10⁵ M^-11 and binding stoichiometry of 1:1.（3）Complex 3 behaved as a prominent photophysical"light switch"for Pu27 G-quadruplex DNA with 15-fold fluorescence enhancements at binding saturation in K⁺buffer,although it could not induce Pu27-mer to form quadruplex structure.3.The binding properties of complexes 1 and 2 to yeast RNA have been studied by electron absorption spectra,fluorescence spectra,steady-state fluorescence quenching and salt effect.Observations revealed that:Complexes 1 and 2 bond to yeast RNA by intercalation mode,and the binding constants were K_b（1）=4.47×10⁵ M^-11 and K_b（2）=1.68×10⁷ M^-1,with binding strength 2>1;In contrast to obviously increased emission intensities for ct-DNA binding of the complex 1 and 2（I/I₀=2.47,1.6）,the fluorescence intensity of complex 1decreased evidently（I/I₀=0.59）and that of complex 2 first increased and then decreased in aqueous solution upon binding to RNA,which indicated that complex 1 and 2 displayed potential fluorescence recognition properties between RNA and DNA.