Comparative Studies On Interactions Of Ruthenium (?) Polypyridyl Complex Enantiomers With Biomacromolecules

In the field of cancer medicine,many researchers are looking for metal complexes with higher efficacy and lower side effects that can replace platinum complexes as anticancer drugs.Among them,aryl ruthenium complexes have been regarded as the potential excellent anticancer agents due to their targeting,low toxicity with high antitumor activity.In this thesis,a pair of bioactive enantiomers of a chiral ruthenium?II?polypyridyl complex with MBIP?MBIP=2-?3-bromophenyl?imidazo[5,6-f]phenanthroline?as its main ligand,?-[Ru?bpy?₂MBIP]²⁺and?-[Ru?bpy?₂MBIP]²⁺were designed and synthesized,and characterized by mass spectrometry?MS?,elemental analysis?EA?and nuclear magnetic resonance?NMR?.Multiple spectroscopic methods including UV-Vis spectrometry,fluorescence and circular dichroism spectroscopy,along with biophysical research methods such as viscosity measurement,and computer molecular simulation techniques were applied for the comparative studies on the interactions of the two enantiomers with human serum albumin?HSA?and calf thymus deoxyribonucleic acid?CT DNA?,respectively.The experimental results showed that both the enantiomers?-[Ru?bpy?₂MBIP]²⁺and?-[Ru?bpy?₂MBIP]²⁺induced the fluorescence quenching of HSA with a static quenching mode and the circular dichroism spectra showed that the interactions between two enantiomers and HSA led to changes in the secondary structure of HSA.The calculated binding constants and the number of binding sites of the two enantiomers to HSA indicated that the?-enantiomer binds to HSA more avidly than the?-enantiomer does,and that there is just one binding site existing for both the two enantiomers to HSA.The thermodynamic analysis further suggested that the interactions of the two enantiomers with HSA are spontaneous processes and the main forces stablizing the enantiomer-HSA complexes are hydrogen bonds or vant der Waals forces.In addition,the experimental results also showed that the binding of the chiral complex[Ru?bpy?₂MBIP]²⁺to right-handed helix CT-DNA is stereoselective.The calculated binding constants demonstrated that the?-enantiomer can bind to DNA preferentially.And the viscosity measurements indicated that the two enantiomers bind to DNA via intercalation.The thermodynamic analyses suggested that the interactions of the two enantiomers with HSA are spontaneous processes and the main forces stablizing the enantiomer-HSA complexes are hydrogen bonds or vant der Waals forces.The computer simulations were performed to investigate the interaction mode of the two enantiomers?-[Ru?bpy?₂MBIP]²⁺and[Ru?bpy?₂MBIP]²⁺with HSA and CT-DNA respectively.The docking results comfirmed the above experimental results and also showed that?-[Ru?bpy?₂MBIP]²⁺binds to both HSA and DNA more strongly.The main forces between the enantiomers and HSA are van der Waals force,and their binding modes to DNA are intercalation.All the above comparative studies suggested that?-[Ru?bpy?₂MBIP]²⁺can bind more strongly to both the transport protein in human body and the targeted DNA,and HSA the potential to treat cancer with a better efficiency.This research work should be helpful to the understanding of the relationship between the structures and chemical properties of metal complexes,thus useful to the design and development of potential anti-cancer drugs of ruthenium complexes with highly effective and low-toxicity.