EFFECTS OF QUINOLINE AS LIGAND IN BINDING OF MONONUCLEAR AND DINUCLEAR PLATINUM COMPLEXES TO DNA

The DNA binding and interstrand cross-linking properties of trans- and cis-[PtCl2(NH3)(quinoline)] (I and II, respectively) and a quinoline- substituted dinuclear platinum compound [{trans-PtCl(NH3)(quin)}2H2N(C H2)(6)NH2](NO3)(2) (III) are reported. The dinuclear compound was exam ined also for its ability to cause conformational changes in poly[(dG- dC)]. poly[(dG-dC)]. For DNA binding studies a UV spectrophotometric m ethod of r(b) determination has been used, allowing measurement of the concentration of a platinum complex bound to DNA using UV absorbance of a ligand, in this case, quinoline. Comparison was made with atomic absorption (AAS) measurements of Pt determination which showed valid a greement between the two methods. In the case of mononuclear complexes , geometry plays an important role in binding as proved by increased b inding of the trans- over the cis-isomer. For the dinuclear complex, b inding saturates at concentrations of approximately 150-200 mu M reach ing the level of relative binding of r(b) similar to 0.25. Interstrand cross-linking of the dinuclear compound was compared with [(trans-PtC l(NH3)(2)}2H2N(CH2)(6)NH2](NO3)(2) (IV). Bath dinuclear compounds show ed similar and very strong interstrand cross-linking efficiency. Bindi ng of III to poly[(dG-dC)]. poly[(dG-dC) changes intensities and shape s of both positive and negative bands of the polymer CD spectrum, alth ough the overall behavior of these changes indicates that the polynucl eotide remains in the B conformation.