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

A series of compounds of general formula [Ru(eta(6)-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)) have been prepared and characterized by spectroscopic methods. The structure of [Ru(eta(6)-p-cymene)(pta)Cl(P(p-C6H4F)(3))]BF4 has also been established in the solid state by X-ray crystallography. The cytotoxicities of the compounds were determined 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 were found to be thermoresponsive, that is, showing poor water solubility at 37 degrees C and good solubility at 42 degrees C, the temperature of a heated tumor, providing a method of tumor targeting. Incubation at 42 degrees C for 2 h resulted in improved cytotoxicities for two of the complexes.