Study On Interaction Mechanism Of Drug With DNA By Chemometrics And Spectrometry Techniques

This thesis is divided into five parts. The research actuality of interaction between some small clinical drugs molecules with DNA in recent years has been reviewed and the binding modes between and pesticide with DNA were studied. The application of chemometrics in analysis of two-dimensional and three- dimensional data also had been developed. And the application of chemometrics in complicated biochemical system (probe-DNA-small molecular) can solve some problems and obtain the equilibrium concentration and pure spectra of each component.Part IIn part one, the chemical and biological characters of DNA were introduced simply first, then the research methods, research objects and binding modes of interaction between small molecules and DNA were reviewed in turns. DNA is the basic genetic material of all organisms and the main target of some drugs in the organism, and study on it has become an important research field of life science. Along with more attention has been given on the research of the interaction between DNA and small molecules, the mechanisms of the action of some drugs and origins of some diseases have generally been understood. Moreover, the investigation based on DNA interactions with small molecular compounds also has great significance to design new DNA-targeted drugs and to screen these drugs in vitro. At last, the development trend was forecasted and exploiting new probes, using various techniques simultaneously and the use of chemometrics were chosen as the emphasis of this thesis.Part IIIn part two, the interaction mechanism between NR and DNA has been studied by use of fluorescence spectroscopic in combination with Singular value decomposition. There is a large excess of the double-stranded DNA in the interacting system, and the determination methods of the binding constant 1.47×10~4(pH 7.4) are based on enhancement of the drug fluorescence.Part IIIIn part three, we have shown that with the use of UV-vis spectrophotometry and fluorescence spectroscopy techniques. The pharmaceutical drug, BER, intercalates into the DNA double helix in combination with polarization and fluorescence quenching measurements.The results presented in this paper describe quantitatively and qualitatively the process of BER binding to DNA. When different correlated-data matrices are simultaneously analyzed by the MCR-ALS, selectivity conditions reduce rotational ambiguities and resolve the problem of rank deficiency. In addition, the mole ratio method was used for monitoring complex in solution and determining formation constants logk_a=5.1 and the formation of 1:1 weak complex. Finally, the value of similarity showed that the resolved pure spectra were close to the true spectra very much. Using the advantages of this chemometric techniques combined the mole ratio method, time and solvent expenses were not only reduced, but the determinations were also improved.Part IVIn part four, The interaction of fuchsin basic (FB) with DNA in aqueous medium has been studies by resonance light scattering (RLS), UV-VIS Spectrum and cyclic voltammograms (CV). The Quantitative and qualitative information was obtained from the mole-ratio methods which monitored the spectra changes of FB-dsDNA interaction. Without postulating a chemical model of the intercalation equilibrium previously, we have show the use of chemometric approaches to enumerate the number of components in the system and monitor the profiles of each component concentration corresponding to pure spectra in the reaction.Deduced from the data of resonance light scattering (RLS), UV-VIS Spectrum and cyclic voltammograms, there were two different interaction mechanism involved in the whole interaction process depending on the R-values (R: the molar ratio of FB to DNA) at pH-7.4. The value R=0.7 is the turning point; when R<0.7, enhanced RLS was observed, which indicated long range assembly of FB on the DNA molecular surface. In this process long-range assembly is the main binding mode. The second process occurs when R>0.7, where FB intercalated into the DNA helix, the intercalative binding is predominant, supported by cyclic voltammograms.