SYNTHESIS OF DINITROXYL CIS-DIAMINOPLATINUM(II) COMPLEXES AND THEIR INTERACTION WITH DNA

Dinitroxyl complexes of platinum, cis-Pt-II(APO)(2)X-2, where APO is 4 -amino-2,2,6,6-tetramethylpiperidine- 1-oxyl, were obtained by either a direct reaction of APO with K2PtX4 (X = Cl or I) or a replacement of iodide ligands in cis-Pt-II(APO)(2)I-2 by nitrate and oxalate ligands . The interaction of water-soluble cis-Pt-II(APO)(2)(NO3)(2) with ox s pleen DNA resulted in platinated DNA with a degree of modification (r) similar to 7 times lower than that obtained with cis-Pt-II(NH3)(2)Cl- 2 (cisplatin). Melting point T-m, melting range Delta T, and the degre e of hyperchromicity Delta H for platinated DNA showed that for equal r values, the cis-Pt-II(APO)(2)-DNA adducts increase heterogeneity in the DNA structure much more effectively than the cis-Pt-II(NH3)(2)-DNA adducts. Poor platinating activity, substantial disturbance of the DN A structure, as well as low toxicity and moderate antitumor activity o f cis-Pt-II(APO)(2)X-2 complexes are probably explained by steric hind rances caused by two bulky APO ligands.