ACID-BASE AND METAL-ION-BINDING PROPERTIES OF THE QUATERNARY [CIS-(NH3)(2)PT(DGUO)(DGMP)] COMPLEX FORMED BETWEEN CIS-DIAMMINEPLATINUM(II), 2'-DEOXYGUANOSINE (DGUO), AND 2'-DEOXYGUANOSINE 5'-MONOPHOSPHATE (DGMP(2-)) IN AQUEOUS-SOLUTION

For the first time the acid-base properties of a quaternary Pt-II comp lex, [cis-(NH3)(2)Pt(dGuo)(dGMP)], are evaluated, as are the quinterna ry complexes resulting from its affinity for further metal ions. To th is end the acid-base properties of dGMP(2-) (ref. [17]), dGuo, and of the quaternary complex resulting from their coordination to cis(NH3)(2 )Pt2+ were determined by potentiometric pH titrations. Owing to the pr esence of the N7-coordinated cis(NH3)(2)Pt(dGuo)(2+) moiety, the relea se of the proton from the -P(O)(2)(OH)(-) group of [H(cis-(NH3)(2)Pt(d Guo)(dGMP)}](+) is favored by Delta pk(a) = 0.34 compared with H(dGMP) -(pK(H(dGMP))(H) = 6.29). The two H(N1) sites in the quaternary comple x are on average acidified by Delta pK(a) approximate to 0.8 compared with the acidity constants of the free ligands (pK(dGuo)(H) = 9.24; pK (dGMP)(H) = 9.56). A similar acidification is to be expected in DNA fo r intrastrand crosslinks by cis-(NH3)(2)Pt2+ between two guanine resid ues; that is, at physiological pH (7.4) some deprotonation of H(N1) si tes (ca. 6%) is already possible in principle. The stability constants of quinternary [M{cis(NH3)(2)Pt(dGuo)(dGMP)}](2+) complexes (M = Mg2, Cu2+, Zn2+) were also measured by potentiometric pH titrations, It i s shown that the metal-ion-coordinating properties of the -PO32- group of the [cis-(NH3)(2)Pt(dGuo)(dGMP)] species are slightly inhibited, c ompared with the coordination tendency expected on the basis of its ba sicity. This inhibition is attributed to repulsion by the N7-coordinat ed Pt-II, which is somewhat more pronounced for M2+ than for H+. Howev er, it is moderate (about -0.2 log units), and therefore, with regard to DNA, one may conclude that cis-(NH3)(2)Pt2+ coordinated to N7 of gu anine residues affects the metal-ion-binding properties of the DNA pho sphate backbone only slightly. This result is of further significance regarding individual nucleotides if these interact as substrates in en zymic reactions with different metal ions through their nucleobase as well as their phosphate residue.