CIS-DIAMMINEPLATINUM(II) FORMS A MACROCHELATE WITH 2'-DEOXYCYTIDINE 5'-MONOPHOSPHATE (DCMP2-) - REACTIVITY AND ACID-BASE PROPERTIES OF CIS-PT(NH3)(2)(DCMP)

The synthesis of cis-Pt(NH3)(2)(dCMP) is reported and by various physi co-chemical methods it is demonstrated that it is a macrochelate in wh ich Pt(II) is bound simultaneously to the N3 site of cytosine in dCMP( 2-) and to a phosphate-oxygen atom. According to the NOESY spectra (cr oss-peaks between cytosine H6 and H2' and H3') the cytosine ring adopt s an anti orientation. Highly unusual is the significant (1 ppm) downf ield shift of the sugar proton H5 '' in the H-1-NMR spectrum and the s ensitivity of the cytosine H6 resonance on the protonation state of th e phosphate group. Based on these three features a geometry for the ma crochelate is proposed. The compound is a major product of the reactio n of cis-[Pt(NH3)(2)(H2O)(2)](2+) with applying pD-dependent NMR spect roscopy (H-1, P-31) and potentiometric pH titration. it is demonstrate d that the Pt-coordinated phosphate group can be protonated (pK(a/1)=3 .21 +/- 0.10 and 3.31 +/- 0.05, respectively), and H-1- and P-31-NMR s pectra also indicate deprotonation (pK(a/2)=13.35+/-0.25) of the exocy clic amino group of the cytosine moiety. The metal ion binding affinit y of cis-Pt(NH3)(2)(dCMP) is very small, as shown for Cu2+ (log K < 0. 6). The cis-Pt(NH3)(2)(dCMP) complex reacts with nucleosides and nucle otides (L') by losing its chelate structure and forming mixed ligand c omplexes, cis-Pt(NH3)(2)(dCMP)(L'); this means that the phosphate grou p is released from the coordination sphere of Pt(II), indicating that the Pr(II)-O(phosphate) bond is not very strong.