CIS-DIAMINEDICHLOROPLATINUM(II) COMPLEXES REVERSIBLY BOUND TO WATER-SOLUBLE POLYASPARTAMIDE CARRIERS FOR CHEMOTHERAPEUTIC APPLICATIONS .2. PLATINUM COORDINATION TO ETHYLENEDIAMINE LIGANDS ATTACHED TO POLY(ETHYLENE OXIDE)-GRAFTED CARRIER POLYMERS

In continuation of previous investigations aiming at the development o f macromolecular metal complexes for biomedical use, this communicatio n describes poly(alkylene oxide)-grafted polymeric platinum complexes. The platinum-containing macromolecules are obtained from presynthesiz ed polyaspartamide carriers bearing poly(ethylene/propylene oxide) sid e chains and hydroxyethyl side groups as hydrosolubilizing units in ad dition to ethylenediamine side group terminals for metal coordination. Platination is brought about by treatment of the carriers with tetrac hloroplatinate(II) ion in aqueous solution at 25-60 degrees C, pH 4-6. The polymeric products, purified by dialysis in aqueous solution, are isolated by freeze-drying in yields of 60-80%. Platinum contents are in the range of 4-15%. The metal is bound to the carrier through chela tion with the ethylenediamine ligands, forming square-planar cis-dichl oroethylenediamine-platinum(II) complex species as side-chain terminal s. Initially, the product polymers dissolve smoothly in water. Althoug h on room-temperature storage in the solid state they gradually turn i nsoluble as a consequence of intermolecular solid-state interaction, s olubility is retained on low-temperature storage and in frozen aqueous solutions.