QUANTIFICATION OF OUTER-SPHERE MACROCHELATE FORMATION IN THE TERNARY CIS-DIAMINE-PLATINUM(II)-BIS-2'-DEOXYGUANOSINE 5'-MONOPHOSPHATE COMPLEX, CIS-(NH3)(2)PT(DGMP)(2)(2-), AND FORMATION OF QUATERNARY MIXED-METAL ION SPECIES WITH MAGNESIUM(II), COPPER(II), OR ZINC(II) IN AQUEOUS-SOLUTION

The acid-base properties of cis-(NH3)(2)Pt(dG)(2)(2-), where both dG(2 -) (=2'-deoxyguanosine 5'-monophosphate) are N7-coordinated to the sam e Pt(II) [the complex is abbreviated as Pt(dG)(2)(2-)], are summarized [on the basis of potentiometric pH titration data from B. Song et al. (Metal-Based Drugs 1996, 3, 131-141)] and a micro acidity constant sc heme is developed which allows quantification of the intrinsic acidity of the two P(O)(2)(OH)(-) groups present in this ternary complex (I = 0.1 M, NaNO3; 25 degrees C). On the basis of comparisons with the cor responding acid-base properties of cis-(NH3)(2)Pt(dCMP . H-N3)(2) [(dC MP . H)(-) = phosphate-monoprotonated 2'-deoxycytidine 5'-monophosphat e] it is concluded that intramolecular, outer-sphere macrochelates for m via Pt(NH3)... O3P hydrogen bonds. The formation degree of these mac rochelates is quantified; it amounts in aqueous solution in each case (in its lower limit) to about 40% for the various possibilities which exist for the formation of these chelates in the cis-(NH3)(2)Pt(dG)(2) complexes. The stability constants of the mixed metal ion complexes, M[Pt(H;dG)(dG)](+) and M[Pt(dG)(2)], were also determined via potentio metric pH titrations. On the basis of previous measurements with simpl e phosphate monoesters and phosphonate derivatives, i.e., R-PO32- with R being a noncoordinating residue (Sigel, H.; et al., Helv. Chim. Act a 1992, 75, 2634-2656), it is shown that the stability of the two mixe d metal ion complexes is largely governed by the basicity of the phosp hate groups las quantified via the mentioned microconstants) indicatin g that the effect of the N7-bound Pt(II) on the phosphate-metal ion bi nding properties is relatively small. These results suggest that, e.g. , a metal ion bound to a nucleobase residue in a nucleotide or in a nu cleic acid affects only slightly the metal ion binding capabilities of its phosphate residue or its phosphate backbone.