RT Journal Article
T1 Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes
A1 Terán More, Aaron
A1 Ferraro, Giarita
A1 Imbimbo, Paola
A1 Sánchez Peláez, Ana Edilia
A1 Monti, Daria Maria
A1 Herrero Domínguez, Santiago
A1 Merlino, Antonello
AB Paddlewheel 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 metalloenzymes
PB Elsevier
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/88236
UL https://hdl.handle.net/20.500.14352/88236
LA eng
NO Project S2017/BMD-3770-CM
NO GRFN32/23 and Program PR3/23
NO CT63/19-CT64/19
NO EB25/22
NO Comunidad de Madrid
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 4 oct 2024