Remarkable lack of biological activity exhibited by a dna-reactive and water-soluble cis-bis(phosphino) platinum(II) complex

Abstract

The solvolytic behaviour of the complex cis-[Pt(PMe₃)₂Cl₂] was investigated in water and dimethyl sulfoxide. Mono-and bis-solvento species have been characterized mainly by ³¹P NMR spectroscopy. The water-soluble species cis-[{Pt(PMe₃)₂(µ-OH)}₂]²⁺, thermodynamically stable at physiological pH values and known to be reactive with pyrimidinic nucleobases, is found to be also quite reactive with purified single- and double-strand DNA, as shown by ³¹P NMR spectroscopy. However, the same hydroxo complex is found to be remarkably inactive towards Eagle's KB cell line and Ehrlich's ascitic tumour cells. This lack of biological activity is maintained also when the complex is administered to Eagle's KB cell line as a suspension of L-α-dipalmitoylphosphatidylcholine liposomes.