(Pentamethylcyclopentadienato) rhodium Complexes for Delivery of the Curcumin Anticancer Drug

Rh-III(*Cp) Cl( X,Y)] (n+) complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 ( 3, Cl- salt; 4, PF6- salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1] decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1-)} were synthesized from [Rh(*Cp)(mu-Cl) Cl] 2 (1). While 2-5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but at 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (Xray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. This aspect warrants further research.