NEW ANTITUMOR PLATINUM COMPOUNDS LINKED TO AMINO PHOSPHONIC-ACIDS WHICH LOSE THE PHOSPHONATE AND TERTIARY AMINE LIGAND UPON BINDING TO NUCLEIC-ACIDS

The interaction of the antitumor active platinum phosphonato complexes [cis-Pt(NH3)2(ntmp)] and [Pt(R,S-dach)(ntmp)] (ntmp = nitrilotris(met hylenephosphonic acid), dach = diaminocyclohexane) with (oligo)nucleot ides has been investigated using H-1 NMR and P-31 NMR spectroscopy. Fo r both complexes the formation of GN7,GN7 chelates is observed, togeth er with the release of ntmp. First, the platinum-phosphonate bond is b roken, probably by direct attack of the first G-base. The coordination of the second base is accompanied by breakage of the bond between the Pt(II) ion and the tertiary amine ligand, a very unusual observation, as N-donor ligands generally act as nonleaving groups in platinum ant itumor chemistry. For this type of platinum antitumor complexes of whi ch the strucural formula seems to violate the classical structure-acti vity relationships, both pH and nonleaving amine group do influence th e rate of the reaction with (oligo)nucleotides significantly.