Leonor Côrte-Real

The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds.

A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA=human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η(5)-C5H5)(bipy)(PPh3)][PF6] (7; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing.

Exploring the effect of the ligand design on the interactions between [Ru(η5-C5H5)(PPh3)(N,O)][CF3SO3] complexes and human serum albumin

Ruthenium complexes hold a great potential in chemotherapy as an alternative to the classical platinum based drugs. The organometallic compounds studied in the present work were previously found to exhibit important anticancer activities. Here we have investigated the binding of three ruthenium compounds, namely [Ru(η(5)-C5H5)(PPh3)(bopy)][CF3SO3] 1, [Ru(η(5)-C5H5)(PPh3)(2-ap)][CF3SO3] 2, and [Ru(η(5)-C5H5)(PPh3)(isoquinpk)][CF3SO3] 3 (bopy=2-benzoylpyridine; 2-ap=2-acetylpyridine; isoquinpk=1-isoquinolinyl phenyl ketone) to fatty acid human serum albumin (HSA) and fatty acid-free human serum albumin (HSA(faf)) at physiological pH7.4. The influence of the substituent groups on the heteroaromatic (N,O) coordinated ligand was also studied by fluorescence spectroscopy to get information about this binding. The Stern-Volmer quenching constants (KSV) were calculated at 293, 298 and 310K, with the corresponding thermodynamic parameters ∆G, ∆H and ∆S as well. The fluorescence quenching method was used to determine the number of binding sites (n) and association constants (Ka) at the same temperatures. The binding site to HSA was confirmed by competitive studies of the ruthenium compounds with warfarin.

Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells

Three new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(η5-MeCp)(PPh3)2Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P1¯. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(η5-MeCp)(PPh3)(L1)][CF3SO3] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent.