Use of Perfluorinated Phosphines to Provide Thermomorphic Anticancer Complexes for Heat-Based Tumor Targeting

[Ru(η6-arene)(pta)(PR3)Cl]BF4 (arene = p-cymene or 4-phenyl-2-butanol; pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, PR3 = PPh2(p-C6H4C2H4C8F17), PPh(p-C6H4C2H4C8F17)2, P(p-C6H4C2H4C6F13)3, PPh3 or P(p-C6H4F)3) were prepd. and characterized by spectroscopic methods. The structure of [Ru(η6-p-cymene)(pta)Cl(P(p-C6H4F)3)]BF4 was established in the solid state by x-ray crystallog. The cytotoxicities of the compds. were detd. in the A2780 and A2780 cisplatin-resistant cell lines revealing that the fluorinated phosphines significantly increase antiproliferative activity relative to their bis-chloride precursors. Two of the complexes are thermoresponsive, i.e., showing poor water soly. at 37° and good soly. at 42°, the temp. of a heated tumor, providing a method of tumor targeting. Incubation at 42° for 2 h resulted in improved cytotoxicities for two of the complexes.