Spectrometric And Electrochemical Studies On The Interaction Of Several Drugs With DNA-the Application Of Chemometrics

This paper reviewed the interaction of some kinds of small molecule with DNA, and combined spectrometric and electrochemical methods with chemometrics to study the interaction of some small molecule with DNA, which can solve some problems, which wasn't resolved by general methods.The work is divided into five parts.Part 1This paper reviewed the importance of DNA in living systems, the structure characteristics of DNA and the binding mode between DNA with different type of some small molecule which can be divided drugs, metallic complex, organic dye probes and surface active agent and so on. On the other hand, a review on the recent advances of the determination of nucleic acids by some methods such as spectrophotometric method, fluorescence method, electrochemical method and other methods, is presented, and the possibility of the application of chemometrics in this field has also been discussed. Finally, the trends on the development between the interaction small molecule with DNA and the further application of chemometrics were looked into the distance.Part 2Interaction of a steroid drug, Ractopamine (RAC), and DNA was investigated by electroanalysis-differential pulse and cyclic voltammetry (DPV and CV). and UV-vis and fluorescence spcctroscopy. DPV showed that RAC was intercalated with DMA, and CV indicated that the reaction mechanism of RAC and dsDNA involved irreversible oxidation with the loss of two H+ and a transfer of two electrons. Reaction binding parameters were obtained. Pure spectra of RAC, DNA and the RAC-DNA complex, and their concentrations were extracted by multivariate curve resolution-alternating least squares method (MCR-ALS). Concentration profiles indicated quantitatively the course of the reaction.Part 3The Interaction of Salbutamol (Sal), an animal growth promoter, with DNA was investigated by differential pulse and cyclic voltammetry (DPV and CV). and fluorescence spcctroscopy. An irreversible reductive behavior can be observed from the CV and the reaction mechanism involved irreversible oxidation with one H+ and one electron. The presence of DNA led to a peak current decreasing and a positive shift of potential for Salbutamol, indicating that Salbutamol could interact with DNA by intercalation mode. Moreover, reaction binding parameters were obtained by treatment of the measured data using multivariate curve resolution-alternating least squares method (MCR-ALS) and the binding constant and ratio were found to be (2.0±0.5)x105 M-1 and 1:1, respectively, In the solution containing 1.00x10-6 mol L-1 dsDNA, determination was performed within a wide concentration range of 3.02x10-6 mol L-1 to 1.23x10-4 mol L-1, and a detection limit of 5.11x10-7 mol L-1 Salbutamol. The method was applied for the determination of Salbutamol in spiked urine and also in spiked human serum samples. No statistically significant differences were observed between the expected and obtained concentrations. The new method is sufficiently sensitive to detect ultra trace amounts of Salbutamol.Part 4The interaction of 10-Hydroxycamptothecine (HCPT) with DNA in physiological Tris-HCl buffer (pH 7.4). using ethidium bromide (EB) dye as a probe, was investigated with the use of fluorescence. UV-vis spectroscopy and viscosity measurements. The binding constant and number of HCPT with DNA were evaluated as (7.1±0.5)x104 M-1 and 1.1 by using multivariate curve resolution-alternating least squares (MCR-ALS). Moreover, parallel factor analysis (PARAFAC) was used to resolve the three-way fluorescence data of the interaction, which provided simultaneously the concentration information for the three components of the system at equilibrium. It was found that there was a cooperative interaction between the HCPT-DNA complex and EB, which produced a ternary complex of HCPT-DNA-EB.Part 5Fluorescence, cyclic voltammetry. and salt effect have been exploited to explore the binding of calf thymus DNA (ctDNA) with three hormones materials, viz., dopamine (DA), levodopa (LDA), and dobutamine (DBTM). A comparative study of the interaction mechanism will relate the material structure. The binding constants between three hormones and DNA were DBTM>LDA>DA by fluorescence quenching interaction, which was the same as the complexity of structure (length of branch chains). Cyclic voltammetry demonstrated that the interaction modes of DA. LDA, DBTM and DNA were electrostatic groove and intercalate interaction, which was proved by salt effect experiment.