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Use of perfluorinated phosphines to provide thermomorphic anticancer complexes for heat-based tumor targeting.

Abstract
A series of compounds of general formula [Ru(eta(6)-arene)(pta)(PR(3))Cl]BF(4) (arene = p-cymene or 4-phenyl-2-butanol; pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, PR(3) = PPh(2)(p-C(6)H(4)C(2)H(4)C(8)F(17)), PPh(p-C(6)H(4)C(2)H(4)C(8)F(17))(2), P(p-C(6)H(4)C(2)H(4)C(6)F(13))(3), PPh(3) or P(p-C(6)H(4)F)(3)) have been prepared and characterized by spectroscopic methods. The structure of [Ru(eta(6)-p-cymene)(pta)Cl(P(p-C(6)H(4)F)(3))]BF(4) 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.
AuthorsAnna K Renfrew, Rosario Scopelliti, Paul J Dyson
JournalInorganic chemistry (Inorg Chem) Vol. 49 Issue 5 Pg. 2239-46 (Mar 01 2010) ISSN: 1520-510X [Electronic] United States
PMID20131860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Organometallic Compounds
  • Phosphines
  • Water
  • Ruthenium
Topics
  • Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
  • Cell Line, Tumor
  • Halogenation
  • Hot Temperature
  • Humans
  • Inhibitory Concentration 50
  • Neoplasms (drug therapy, pathology)
  • Organometallic Compounds (chemistry, pharmacology, therapeutic use)
  • Phosphines (chemistry)
  • Ruthenium (chemistry)
  • Solubility
  • Water (chemistry)

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