Study On The Interaction Between Small Molecule And DNA By Spectroscopy

Deoxyribonucleic acid (DNA) is the biological genetic of the body and is the basis of geneexpression. DNA is important on the synthesis of protein as an important genetic material, so the DNAplays a vital role in the biological life phenomenon. Studying the relationship between the structure andfunction of DNA is beneficial to discuss the nature of the phenomenon of life from the molecular level.Many diseases, such as cancer are due to the infected DNA replication (Chemicals, ultraviolet light, someviruses and environmental factors can make DNA mutate.). Investigates the interaction of small moleculeswith DNA has an important significance in the kinetics of small molecules, biochemistry and clinicalmedicine. The fluorescence spectrometry is widely applied to study the interaction of small molecules withDNA, because it has high, fast and good sensitivity. This thesis is divided into five parts:Part1This part will focus on application and development of ionic liquid, the research situation ofanthraquinone derivative and thiosemicarbazone derivative. The structure of DNA and the interaction ofDNA with small molecule are also studied.Part2and part3:The interaction of1-butyl-3-methylimidazolium methanesulfonate ([C4mim][MS]) and1-hexyl-3-methylimidazolium methanesulfonate ([C6mim][MS]) with calf thymus deoxyribonucleic acid(ctDNA) were investigated by fluorescence spectra and UV absorption spectra. It was important to studythe interaction of ionic liquids (ILs) with DNA for the development of ILs application in life science, andhelp the researchers to choose and design the better ILs to serve as a solvent. Fluorescence quenchingmechanism of [Cnmim][MS](n=4,6) by ctDNA were static quenching type. UV absorption spectra, single-stranded and double-stranded DNA studies, Iodide quenching studies and fluorescence polarizationmeasurements proved that the main interactions between [Cnmim][MS](n=4,6) and ctDNA were groovebinding. Binding constants of ctDNA with [Cnmim][MS](n=4,6) were calculated at different temperatures(285K,298K,310K). Moreover, the binding constants of [C6mim][MS]-ctDNA was larger than[C6mim][MS]-ctDNA, which indicated that the binding force of [C6mim][MS]-ctDNA is larger than[C4mim][MS]-ctDNA. According to the thermodynamic parameters, it showed that hydrophobicinteraction played an important role (at the concentration of study) in the interaction process of ctDNA with[Cnmim][MS](n=4,6). The results allowed us to understand (i) the alkyl chain length of the cation on themechanism of ILs-ctDNA interaction and (ii) the effect of the alkyl chain length of the cation on thebinding constant of ILs–ctDNA interaction.Part4: Spectroscopic study one thiosemicarbazone derivative with ctDNA using ethidium bromide asa fluorescence probeIn this study, a thiosemicarbazone derivative(E)-2-((1,4-dihydroxy-9,10-anthraquinone-2-yl)methylene)-N-(4-fluorophenyl)hydraz-inecarbothioamide(DAFPT) was synthesized, and the interaction of DAFPT with calf thymus DNA (ctDNA) was exploredusing ethidium bromide (EB) as a fluorescence probe. The binding mode between DAFPT and ctDNA wasinvestigated by UV absorption spectroscopy, fluorescence spectroscopy and molecular docking. Thefluorescence quenching mechanism of EB-ctDNA by DAFPT might be a combined quenching type.Thermodynamic parameters showed that the reaction was spontaneous. According to ionic strength,fluorescence polarization and melting temperature (Tm) curve results, DAFPT-ctDNA interaction wasgroove binding. The molecular modeling results indicated that DAFPT could sl ide into the A–T rich regionof ctDNA. Part5: Interaction of one anthraquinone derivative with ctDNA analyzed by spectroscopic andmodeling methodsThe interaction of one anthracycline (AOMan) with calf thymus deoxyribonucleic acid (ctDNA) wassystematically investigated at physiological pH7.4by fluorescence spectroscopy and molecular modeling.Binding constants of ctDNA with AOMan were calculated at different temperatures. Thermodynamicparameters, enthalpy and entropy changes were calculated according to Van’t Hoff equation, whichindicated that the reaction was spontaneous and predominantly enthalpically driven. The increasingviscosity of ctDNA indicated that AOMan could intercalate into the base pairs of ctDNA. Furthermore, themolecular modeling results showed that anthracycline ring tended to slide into the G–C rich region ofctDNA through the hydrogen bond, which are consistent with the results from experimental methods.Studying the binding interaction of target anthracycline with DNA is one of the key steps in theirDNA-changing action and the design of new drugs.