The Interaction Of Ruthenium Complexes With Triplex RNA

Triplex RNA has potential roles in vivo and has been implicated in a range of cellular functions such as transcriptional regulation,post–transcriptional RNA processing,modification of chromatin and DNA repair,which help us further understand their potential applications in genome biology and regulation.However,the relatively low stability of negatively charged triplex RNA strands due to electrostatic repulsion between them is a key limitation of their application in vivo.Therefore,small molecules having the ability to recognize,bind and stabilize specific sequences of triplex structures are of particular interest.Given that among the metal complexes Ruthenium(?)polypyridyl complexes have a combination of easily constructed three spatial dimension structures and abundant photophysical properties,and the use of chiral Ru(?)complexes to detect the structure of nucleic acid is an active field.Therefore,the paper synthesizes and characterized a few of Ru(?)complexes,their binding properties and stabilized effect toward triplex RNA were studied.The content is divided into the following five parts:The first chapter summarizes the research progress of triplexes nucleic acid,the interaction mechanism of metal complexes with triplex RNA,the research methods,and prospect.In the second chapter,two chiral Ru(?)complexes?/?-1 were designed,the auxiliary ligand and major ligand are bpy and 7-CF₃-dppz.Their interaction with triplex RNA was studied by spectroscopic,thermal transformation technology,and hydrodynamic methods.The results show that the binding affinity of the two enantiomers is almost the same,and bind to triplex RNA by an intercalation mode.However,there are differences between the two enantiomers in the stabilization of triplex RNA.That may be due to the interaction between?/?-1 and the chiral environment of nucleic acid through different orientations.In the third chapter,two chiral Ru(?)complexes?/?-2 were synthesized,the major ligand is dppx,and the binding of?/?-2 with triplex RNA was studied.The spectroscopic tests show that the binding strength of the?/?-2 to the triplex RNA is only slightly different,which is also supported by the viscosity.Although there is little difference in the binding strength of the two enantiomers,and both bind to the triplex RNA by the intercalation mode,there is a significant difference in the stabilization of the third strand between?-2 and?-2,which may be due to the high spatial matching between the?-2 and the triplex RNA.The forth chapter,three Ru(?)complexes(43)/(35)/rac-3 were designed,the major ligand is ptip.Spectroscopic tests show that the binding strength of?-3 to triplex RNA is slightly higher than that of?-3 and rac-3.They have a certain degree of stability to the third strand.However,the stability of?-3 to the template double strand increases with the increase of the C_Ru/C_UAU ratio,?-3 destabilizes the template double strand,rac-3 destabilizes the template double strand when the concentration of the complex is low,this is due to the different binding effects of different structures.In the last chapter,two new arene Ru(?)complexes Ru1 and Ru2 were designed and characterizes.Studies under the used conditions show no significant difference in binding affinity with triplex RNA,and both bind to the triplex RNA by the intercalation mode,but there is a significant difference in the stability.Ru1 is more inclined to selectively stabilize the third strand,while Ru2 is slightly more stable to the template double strand.These results may be due to the fact that trifluoromethyl is an electron-absorbing group,which reduces the electron density of the ligand,increases the positive charge,and improves the binding ability of the complex with triplex RNA.The arene ring in the auxiliary ligand is hydrophobic,the halogen is the leaving group,and the arene ring determines the electron distribution of the arene Ru(?)complex and affects the stability of the arene Ru(?)complex.