8PH6

X-ray structure of the adduct formed upon reaction of Lysozyme with K2[Ru2(DPhF)(CO3)3] in condition B

Summary for 8PH6

• Entry DOI: 10.2210/pdb8ph6/pdb
• Descriptor: Lysozyme C, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, [Ru2(DPhF)(Formate)(CO3)], ... (7 entities in total)
• Functional Keywords: ruthenium, protein interaction, metallodrug, diruthenium, hydrolase, protein binding
• Biological source: Gallus gallus (chicken)
• Total number of polymer chains: 1
• Total formula weight: 16661.15

Authors

Teran, A.,Ferraro, G.,Merlino, A. (deposition date: 2023-06-19, release date: 2023-09-13, Last modification date: 2023-09-20)

Primary citation

Teran, A.,Ferraro, G.,Imbimbo, P.,Sanchez-Pelaez, A.E.,Monti, D.M.,Herrero, S.,Merlino, A.
Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes.
Int.J.Biol.Macromol., 253:126666-126666, 2023

PubMed Abstract: 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, [RuCl(DPhF)(OCCH)], and two derivatives, [RuCl(DPhF)(OCCH)] and K[Ru(DPhF)(CO)] (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 Ru 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.

PubMed: 37660867
DOI: 10.1016/j.ijbiomac.2023.126666

Experimental method

X-RAY DIFFRACTION (1.07 Å)