8ph6
X-ray structure of the adduct formed upon reaction of Lysozyme with K2[Ru2(DPhF)(CO3)3] in condition B
Structural highlights
FunctionLYSC_CHICK Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1] Publication Abstract from PubMedPaddlewheel 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, [Ru(2)Cl(DPhF)(2)(O(2)CCH(3))(2)], and two derivatives, [Ru(2)Cl(DPhF)(O(2)CCH(3))(3)] and K(2)[Ru(2)(DPhF)(CO(3))(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 Ru(2)(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. Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes.,Teran A, Ferraro G, Imbimbo P, Sanchez-Pelaez AE, Monti DM, Herrero S, Merlino A Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126666. doi: , 10.1016/j.ijbiomac.2023.126666. Epub 2023 Sep 1. PMID:37660867[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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