Person: Sánchez Peláez, Ana Edilia
Loading...
First Name
Ana Edilia
Last Name
Sánchez Peláez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Química Inorgánica
Area
Química Inorgánica
Identifiers
3 results
Search Results
Now showing 1 - 3 of 3
Item Effect of Equatorial Ligand Substitution on the Reactivity with Proteins of Paddlewheel Diruthenium Complexes: Structural Studies(Inorganic Chemistry, 2023) Terán More, Aaron; Ferraro, Giarita; Sánchez Peláez, Ana Edilia; Herrero Domínguez, Santiago; Merlino, AntonelloThe paddlewheel [Ru2Cl(O2CCH3)4] complex was previously reported to react with the model protein hen egg white lysozyme (HEWL), forming adducts with two diruthenium moieties bound to Asp101 and Asp119 side chains upon the release of one acetate. To study the effect of the equatorial ligands on the reactivity with proteins of diruthenium compounds, X-ray structures of the adducts formed when HEWL reacts with [Ru2Cl(D-p-FPhF)(O2CCH3)3] [D-p-FPhF = N,N′-bis(4-fluorophenyl)formamidinate] under different conditions were solved. [Ru2Cl(D-p-FPhF)(O2CCH3)3] is bonded through their equatorial positions to the Asp side chains. Protein binding occurs cis or trans to D-p-FPhF. Lys or Arg side chains or even main-chain carbonyl groups can coordinate to the diruthenium core at the axial site. Data help to understand the reactivity of paddlewheel diruthenium complexes with proteins, providing useful information for the design of new artificial diruthenium-containing metalloenzymes with potential applications in the fields of catalysis, biomedicine, and biotechnology.Item Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes(International Journal of Biological Macromolecules, 2023) Terán More, Aaron; Ferraro, Giarita; Imbimbo, Paola; Sánchez Peláez, Ana Edilia; Monti, Daria Maria; Herrero Domínguez, Santiago; Merlino, AntonelloPaddlewheel diruthenium complexes are being used as metal-based drugs. It has been proposed that their charge and steric properties determine their selectivity towards proteins. Here, we explore these parameters using the first water-soluble diruthenium complex bearing two formamidinate ligands, [Ru2Cl(DPhF)2(O2CCH3)2], and two derivatives, [Ru2Cl(DPhF)(O2CCH3)3] and K2[Ru2(DPhF)(CO3)3] (DPhF− = N,N′-diphenylformamidinate), with one formamidinate. Their protein binding properties have been assessed employing hen egg white lysozyme (HEWL). The results confirm the relationship between the type of interaction (coordinate/non-coordinate bonds) and the charge of diruthenium complexes. The crystallization medium is also a key factor. In all cases, diruthenium species maintain the M–M bond and produce stable adducts. The antiproliferative properties of these diruthenium complexes have been evaluated on an eukaryotic cell-based model. Our data show a correlation between the number of the formamidinate ligands and the anticancer activity of the diruthenium derivatives against human epithelial carcinoma cells. Increased cytotoxicity may be related to increased steric hindrance and Ru2 5+ core electronic density. However, the effect of increasing the lipophilicity of diruthenium species by introducing a second N,N′-diphenylformamidinate must be also considered. This work illustrates a systematic approach to shed light on the relevant properties of diruthenium compounds to design metal-based metallodrugs and diruthenium metalloenzymesItem A Diruthenium Metallodrug as a Potent Inhibitor of Amyloid-β Aggregation: Synergism of Mechanisms of Action(Inorganic Chemistry, 2024) La Manna, Sara; Di Natale, Concetta; Panzetta, Valeria; Leone, Marilisa; Mercurio, Flavia ; Cipollone, Irene; Monti, Maria; Netti, Paolo ; Ferraro, Giarita; Terán More, Aaron; Sánchez Peláez, Ana Edilia; Herrero Domínguez, Santiago; Merlino, Antonello; Marasco, DanielaThe physical and chemical properties of paddlewheel diruthenium compounds are highly dependent on the nature of the ligands surrounding the bimetallic core. Herein, we compare the ability of two diruthenium compounds, [Ru2Cl(D-p-FPhF)- (O2CCH3)3]·H2O (1) (D-p-FPhF− = N,N′-bis(4-fluorophenyl)- formamidinate) and K3[Ru2(O2CO)4]·3H2O (2), to act as inhibitors of amyloid aggregation of the Aβ1−42 peptide and its peculiar fragments, Aβ1−16 and Aβ21−40. A wide range of biophysical techniques has been used to determine the inhibition capacity against aggregation and the possible mechanism of action of these compounds (Thioflavin T fluorescence and autofluorescence assays, UV−vis absorption spectroscopy, circular dichroism, nuclear magnetic resonance, mass spectrometry, and electron scanning microscopy). Data show that the most effective inhibitory effect is shown for compound 1. This compound inhibits fiber formation and completely abolishes the cytotoxicity of Aβ1−42. The antiaggregatory capacity of this complex can be explained by a binding mechanism of the dimetallic units to the peptide chain along with π−π interactions between the formamidinate ligand and the aromatic side chains. The results suggest the potential use of paddlewheel diruthenium complexes as neurodrugs and confirm the importance of the steric and charge effects on the properties of diruthenium compounds