Study On The Interaction Mechanism Of Anti-tumor Active Small Molecules And ZnS Shell Quantum Dots With Nucleic Acid Based On Spectral Method

Nucleic acid is an important biological macromolecule,which is the basic genetic material of organism.It is also the main target molecule of most antiviral,antimicrobial and anti-tumor drugs in vivo.The interaction between small molecular drugs and DNA may affect the physiological and physicochemical properties of DNA and alter the transcription and replication of DNA.The interaction between nucleic acid and ligands has become one of the hot fields in biochemistry and life sciences.This is of great significance for the design,pharmacology and toxicity study and clinical detection of new drugs and new nano materials.This thesis consists of five chapters:The first chapter,the composition and structural characteristics of nucleic acid,the main modes of ligand and nucleic acid interaction are briefly introduced.The main methods are spectral method,electrochemical method,molecular simulation and so on.In this paper,the research theory and present situation of various analytical techniques applied in the field of ligand and DNA interaction are reviewed.The second chapter,in this study,the interaction mechanism of three ruthenium arene complexes with curcuminoids with calf thymus DNA(ct DNA)was studied by UV-vis spectrum,fluorescence spectrum,circular dichroism was combined with the viscometry,melting point measurement and electrochemical methods.UV-Vis absorption spectra showed that the UV absorption of the three ruthenium arene complexes with curcuminoids showed slight color reduction and red shift after the addition of ct DNA,while the viscosity and melting point of ct DNA increased with the addition of three ruthenium arene complexes with curcuminoids.Using berberine as a fluorescence probe,it was found that the interaction between three ruthenium arene complexes with curcuminoids and ct DNA was static quenching mechanism.The binding mode was intercalation mode and the Hydrogen bonding and van der Waals force are the main forces,and the electrostatic forces also existed.The binding ability of complex 3 to ct DNA is the strongest,chemical denaturants and thermal denaturation can reduce the intercalation effect between the three ruthenium arene complexes with curcuminoids and ct DNA.Circular dichroism shows that three ruthenium arene complexes with curcuminoids has some influence on the double helix structure of ct DNA,and the effect of complex 3 was the most significant.The electrochemical experiment results further prove that three ruthenium arene complexes with curcuminoids has some effect on the structure of ct DNA.These results may provide useful information for the study of the interaction mechanism between ruthenium arene complexes with curcuminoids antitumor drugs and DNA.The third chapter,the interaction mechanism between quercetin and its metal complexes and ct DNA was systematically studied UV-vis absorption spectra,fluorescence spectra,circular dichroism,viscosity measurement and melting point measurement.UV-vis spectra showed that the UV absorption of quercetin and its metal complexes decreased slightly after adding ct DNA,while the viscosity and melting point of ct DNA increased after the addition of quercetin and its metal complexes.By using acridine orange(AO)as a fluorescence probe,it is found that quercetin and its metal complexes and ct DNA are static quenching mechanisms.The binding mode was intercalation mode,hydrogen bonding and van der Waals force is the main force,and the binding ability of quercetin-Cr(III)to ct DNA is the strongest.Circular dichroism showed that quercetin and its metal complexes had some influence on the double helix structure of ct DNA.Quercetin-Cr(III)had the greatest effect on the structure of ct DNA.The fourth chapter,the interaction of three steroidal derivatives with G-quadruplex DNA sequence d(GGGT)4 and their effects on structures have been studied by spectroscopic method,1H NMR,electrochemical method and molecular simulation techniques.The three steroidal derivatives selectively binding to parallel G-quadruplex DNA by terminal stacking binding mode to form complexes.All the three compounds could stabilize the G-quadruplex structure of DNA to some extent,and compound 3 had the strongest stability,and the three compounds enhanced the biological activity of DNA to some extent.The spatial steric resistance effect is the reason of the difference of the binding action between the G-quadruplex DNA sequence and different steroidal derivatives.These results provide new information for the study of the interaction between steroid derivatives and DNA at the molecular level and the influence on the DNA structure.The fifth chapter,using spectroscopic method combined with electrochemical method,the interaction of two kinds of Zn S shell quantum dots(Cd Se/Zn S,In P/Zn S quantum dots)with G-quadruplex DNA sequence Pu22 and h Tel22 and their effects on their structures were studied.Cd Se/Zn S、In P/Zn S quantum dots have no obvious effect on the configuration of parallel G-quadruplex Pu22 and anti-parallel G-quadruplex h Tel22.The addition of water-soluble QDs decreases the melting temperature of G-quadruplex Pu22 and h Tel22,the stability of parallel G-quadruplex Pu22 structures is greatly affected by the addition of QDs.It is found that the binding ability of Cd Se/Zn S,In P/Zn S quantum dots to G-quadruplex h Tel22 is stronger than that of Pu22.It is found that the binding ability of Cd Se/Zn S,In P/Zn S quantum dots to anti-parallel G-quadruplex h Tel22 is stronger than that of parallel G-quadruplex Pu22.Therefore,quantum dots may be preferentially bound to anti-parallel G-quadruplex.The quenching type of the interaction between Cd Se/Zn S,In P/Zn S quantum dots and parallel G-quadruplex Pu22,anti-parallel G-quadruplex h Tel22 is static quenching.This study provides new information for the interaction of Zn S shell quantum dots with DNA and the effect on the structure of DNA.