Machado, João FrancoMachuqueiro, MiguelMarques, FernandaRobalo, M. PaulaPiedade, M. Fatima M.Garcia, M. HelenaCorreia, João D. G.Morais, Tânia2020-06-182020-06-182020-05-14MACHADO, João Franco; [et al] – Novel "ruthenium cyclopentadienyl" - peptide conjugate complexes against human FGFR(+) breast cancer. Dalton Transactions. ISSN 1477-9234. Vol. 49, N.º 18 (2020), pp. 5974-59871477-9234http://hdl.handle.net/10400.21/11882In this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3)(2,2'-bipy)][CF3SO3] (where Cp = eta(5)-cyclopentadienyl) TM34 towards FGFR(+) breast cancer cells. Molecular dynamics (MD) simulations of TM34 in a phosphatidylcholine membrane model pinpointed the cyclopentadienyl group as a favorable derivatization position for the peptide conjugation approach. Three new Ru(II) complexes presenting a functionalized eta(5)-cyclopentadienyl were synthesized, namely [Ru(eta(5)-C5H4COOH)(2,2'-bipy)(PPh3][CF3SO3] (TM281) and its precursors, [Ru(eta(5)-C5H4COOCH2CH3)(eta(2)-2,2'-bipy)(PPh3)][CF3SO3] (3) and [Ru(eta(5)-C5H4COOCH2CH3)(PPh3)(2)Cl] (2). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the eta(5)-cyclopentadienyl ligand of complex 3 with K2CO3 in water/acetonitrile, followed by mild protonation using an ion exchange resin. The newly synthesized complexes were fully characterized by NMR, FTIR and UV-vis spectroscopic techniques. Also, electrochemical studies were carried out by means of cyclic voltammetry in order to evaluate the stability of the compounds. Single crystal X-ray diffraction studies were carried out for compounds 3 and TM281 which crystallized in the monoclinic system, space group P21/n. The unprecedented synthesis and characterization of three half-sandwich ruthenium(II)-cyclopentadienyl peptide conjugates and their preliminary biological evaluation against human FGFR(+) and FGFR(-) breast cancer cells are also reported.engRuthenium cyclopentadienylMolecular Dynamics (MD)Breast cancerPeptide conjugatejournal article10.1039/d0dt00955e