| Abstract |
Thirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of alpha-amino acids (AA) with [RuCl2(P-P)(N-N)], where P-P = 1,4-bis(diphenylphosphino)butane (dppb) or 1,3-bis(diphenylphosphino)propane (dppp) and N-N = 4,4 -dimethyl-2,2 -bipyridine (4 -Mebipy), 5,5 -dimethyl-2,2 -bipyridine (5 -Mebipy) or 4,4 -Methoxy-2-2 -bipyridine (4 -MeObipy). This afforded a family of complexes formulated as [Ru(AA-H)(P-P)(N-N)]PF6, where AA = glycine (Gly), L-alanine (Ala), L-valine (Val), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His) and L-methionine (Met). All compounds were characterized by elemental analysis, spectroscopic and electrochemical techniques. The [Ru(AA-H)(P-P)(N-N)]PF6 complexes are octahedral (the AA-H ligand binding involves N-amine and O-carboxylate), diamagnetic (low-spin d(6), S = 0) and present bands due to electronic transitions in the visible region. H-1, C-13\H-1\ and P-31\H-1\ NMR spectra of the complexes indicate the presence of C-2 symmetry, and the identification of diastereoisomers. In vitro cytotoxicity assays of the compounds and cisplatin were carried out using MDA-MB-231 (human breast) tumor cell line and a non-tumor breast cell line (MCF-10A). Most complexes present promising results with IC50 values comparable with the reference drug cisplatin and high selectivity indexes were found for the complexes containing L-Trp. The binding of two Ru-precursors of the type [RuCl2(dppb)(N N)] (N-N = 4 -meObipy or 4 -Mebipy) to the blood transporter protein human serum albumin (HSA) was evaluated by fluorescence and circular dichroism spectroscopy. Both complexes bind HSA, probably in the hydrophobic pocket near Trp214, and the Ru-complex containing 4 -MeObipy shows higher affinity for HSA than the 4 -Mebipy one. |
