Acid-base and metal ion-binding properties of 2′-deoxycytidine 5′-monophosphate (dCMP 2−) alone and coordinated to cis-diammine-platinum(II). Formation of mixed metal ion nucleotide complexes

Abstract

The acidity constants of diprotonated 2′-deoxycytidine 5′-monophosphate, i.e. H 2(dCMP) ±, were determined by potentiometric pH titration in aqueous solution (25 °C; I = 0.1 M, NaNO 3) and compared with the previously determined (S.S. Massoud and H. Sigel, Inorg. Chem., 27 (1988) 1447–1453) corresponding constants of diprotonated cytidine 5′-monophosphate, i.e. H 2(CMP) ±. The absence of the 2′-hydroxy group makes dCMP 2− slightly more basic, compared with CMP 2−. The stability constants of the M(H·dCMP) + and M(dCMP) complexes of Mg 2+, Cu 2+ and Zn 2+ were determined and those for the corresponding CMP complexes reevaluated. It is concluded that in the M(H·dCMP) + and M(H·CMP) + species the metal ion is mainly located at N-3 and the proton at the phosphate group. On the basis of recent measurements with simple phosphate monoesters and phosphonate derivatives, i.e. R-PO 3 2− with R being a non-coordinating residue (H. Sigel et al., Helv. Chim. Acta, 75 (1992) 2634–2656), it is shown that the stability of all the M(dCMP) and M(CMP) complexes is solely determined by the basicity of the phosphate group. Coordination of two H(dCMP) − ions via N-3 to cis-(NH 3) 2Pt 2+ gives H 2[ cis-(NH 3) 2Pt(dCMP) 2], abbreviated as H 2(Pt(dC) 2), the synthesis of which is described and the acidity constants of which were determined. Pt 2+ bound to the N-3 sites apparently has only a small effect on the basicity of the two phosphate groups in Pt(dC) 2 2−. In addition, also via pitentiometric pH titrations, the stability constants of the M(H·Pt(dC) 2) + and M(Pt(dC) 2) complexes with Mg 2+, Cu 2+ and Zn 2+ were determined. Based on the previously determined (see the above Ref.) linear log K M(R−PO 3) M versus p K H(R-PO 3) H relationships it is shown that the metal ion-binding properties of the phosphate groups in the mentioned platinum(II) complex are still remarkable, allowing thus the formation of mixed metal ion complexes. In fact, the effect of Pt 2+ at the N-3 sites on the binding properties of the phosphate groups is relatively small; to a first approximation, though there are some minor additional effects, one may conclude that also in these cases the complex stabilities are mainly determined by the basicity of the phosphate groups.