SYNTHESIS, CHARACTERIZATION, DNA-BINDING PROPERTIES, AND SOLUTION THERMOCHROMISM OF PLATINUM(II) COMPLEXES OF THE ETHIDIUM CATION - REGIOSPECIFICITY IN A DNA-PROMOTED REACTION

The reaction of [Pt(NH3).Cl4-n](n-2) (n = 1, 2, and 3) complexes with 1 equiv of the ethidium (Etd) cation afforded cis-[Pt(NH3)2(Etd)Cl]2+, trans-[Pt(NH3)2(Etd)Cl]2+, cis-[Pt(NH3)(Etd)Cl2]+, and [Pt(NH3)3(Etd) ]3+, in which Etd is coordinated to platinum through one of its two ex ocyclic amino groups. These N3 and N8 linkage isomers were separated b y reverse-phase HPLC. The platinum coordination sites on ethidium were determined with the use of both Pt-195 and H-1 NMR spectroscopy as we ll as by single-crystal X-ray diffraction studies of the N3 and N8 iso mers of cis-[Pt(NH3)2(Etd)Cl]Cl2. Solutions of the acetate salts of al l the complexes displayed temperature-dependent optical spectroscopic changes in which a transition at approximately 490 nm (orange) diminis hed in intensity with concomitant growth of a band at approximately 64 0 nm (blue) as the temperature increased. This reversible thermochromi c phenomenon was shown to arise from proton transfer between the coord inated exocyclic amino group and the acetate counterion. Temperature-d ependent electronic spectral changes resulting from this reaction were fit to the appropriate equilibrium expressions by global analysis, yi elding the corresponding thermodynamic parameters, and DELTAS-degrees. Acidity constants for the deprotonation of the coordinated exocyclic amino groups were determined from such equilibrium studies of most of the complexes in methanol and converted to the corresponding values in aqueous solution. These experiments revealed the effects of overall c harge, linkage isomerism, and platinum geometric isomerism on the pK(a ) values of the coordinated amino group. Through a Fenske-Hall molecul ar orbital analysis, the 490-nm band was assigned as a charge-transfer transition from the lone pair orbital of the uncoordinated exocyclic amino nitrogen to the pi orbital (LUMO) of the phenanthridinium ring. The blue band at approximately 640 nm was best described as a charge- transfer transition from a pi orbital delocalized over the Pt-N(coordi nated exocyclicamine) linkage to the pi orbital of the phenanthridini um ring. The ability to assign the relative pK(a) values of the linkag e isomers has been used to demonstrate that the previously reported DN A-promoted reaction between cis-DDP and ethidium is regiospecific, wit h the platinum reacting primarily at the N8 position of the Etd ring.