The Interactions Between Metal Complexes With DNA

The nature and dynamics of binding small molecules to biopolymers represents an area of active investigation. Studies directed toward the design of site- and conformation-specific reagents provided routes toward rational drug design as well as a means to develop sensitive chemical probes of polymer structure. Deoxyribonucleic acid (DNA)is a kind of key biologic large molecule, it plays very important role in life genetic code' interpretation, transcription and copy, it is the primary target molecule for most of anticancer and antiviral therapies according to the cell biology. The investigation of interaction of DNA with other molecules is of great importance in elucidating the structure of DNA and their functions. It is also helpful to understand some diseases and the mechanism by which some medicines (especially antitumor drugs) act. In this thesis the results of interaction of some antitumor compounds with DNA were reported.This thesis consists of three sections as follows:First, fluorescence spectral, agarose gel electrophoresis, viscometric and CD (circular dichroism) were used to study the interaction of the antitumor compounds Y(RA)₂·Ac·8H₂O and Sm(RA)₂·Ac·4H₂O (RA= retinoic acid, )with DNA. The results indicate that the Y(RA)₂·Ac·8H₂O can more effectively promote the cleavage of plasmid DNA than all-trans retinoic acid at physiological pH and temperature, which may be the one of reasons why the inhibitory effect of Y(RA)₂·Ac-8H₂O on human bladder line EJ cells is much greater than that of retinoic acid. We increased ionic strength and changed pH of reaction systems and added radical scavengers and found that the process of plasmid DNA cleavage is sensitive to increasing ionic strength and changing pH, and these radical scavengers almost no any effect on the DNA cleavage reaction. The above results suggest that the cleavage of DNA by Y(RA)₂·Ac·8H₂O was not produced diffusible hydroxyl radicals via the Fenton reaction.On the side, we investigated the interaction of Y(RA)₂·Ac·8H₂O and Sm(RA)₂·Ac·4H₂O with Calf thymus DNA by means of fluorescence spectroscopy, viscometric and CD (circular dichroism). The results show that the emission spectral intensity is decreased and the viscosity of DNA is increased by adding the tow complexes. Increasing fluorescence is seen for the complex with DNA addition. The denatured temperature of DNA is increased and the negativespectra of the CD of DNA is changed by adding Y(RA)₂·Ac·8H₂O. The above results suggest that the tow complexes can bind to DNA mainly by intercalation, which may be the other reason that the complex can inhibit the HL-6CK EJ cancer cell.Second, the interactions of the Cu(II), Ni(II) complexes with all-trans retinoic acid (Cu(RA)₂·3H₂O, Ni(RA)₂·3H₂O) between DNA have been studied using agarose gel electrophoresis. We firstly found the Ni(RA)₂·3H₂O and Cu(RA)₂·3H₂O complexes can promote the cleavage of plasmid DNA at physiological pH and temperature. The Ni(RA)2 -3H2O complex can more effectively promote the cleavage of plasmid DNA than Cu(RA)₂·3H₂O complex, Y(RA)₂·Ac·8H₂O complex, all-trans retinoic acid and Ni²⁺, at the same conditions, and the efficiency of DNA cleavage by Ni(RA)₂·3H₂O complex was rather high and the reaction time was very short, which may be the one of reasons why the inhibitory effect of Ni(RA)₂·3H₂O on human bladder line EJ cells is much greater than that of retinoic acid. Otherwise, we increased ionic strength and changed pH of reaction systems and added radical scavengers and found that the process of plasmid DNA cleavage is sensitive to increasing ionic strength but the pH have almost not effect on the cleavage of DNA, and these radical scavengers almost no any effect on the DNA cleavage reaction. The above results suggest that the cleavage of DNA by Ni(RA)₂·3H₂O was not produced diffusible hydroxyl radicals via the Fenton reaction.In addition, we used to study the interactions of the Cu(RA)₂·3H₂O complex between DNA by fluorescence spectral, viscosity measurements and elect...