Covalent versus Noncovalent Binding of Ruthenium η⁶‐p‐Cymene Complexes to Zinc‐Finger Protein NCp7

Abstract

Ruthenium-arene complexesa re au nique class of organometallic compounds that have been shown to have prominent therapeutic potencies.H ere, we have investigated the interactions of Ru-cymene complexes with az incfinger protein NCp7, aiming to understand the effects of various ligandso nt he reaction. Five different binding modes were observed on selected Ru-complexes. Ru-cymene complex can bind to proteins through either noncovalent binding aloneo rt hrough ac ombinationo fc ovalent and nonco-valentb inding modes. Moreover,t he noncovalent interaction can promote the coordination of Ru II to NCp7, resulting synergistic effects of the different ligands. The binding of Ru(Cym) complexes leads to dysfunction of NCp7 through zinc-ejection and structural perturbation. These results indicate that the reactivityo fR u-complexes can be modulated by ligands through differenta pproaches, which could be closely correlated to their different therapeutic effects.

Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

“…It seems like it is a general trend that chlorido ligand is easier exchanged with water than the pta ligand, i.e., chlorido ligand is more labile than pta. This also affects the kinetics of interactions with biomolecules and thus, also their biological activity [43][44][45].…”

Structural Isomerism and Enhanced Lipophilicity of Pyrithione Ligands of Organoruthenium(II) Complexes Increase Inhibition on AChE and BuChE

“…In our previous studies, we have found that the behavior of the complexes depends on the type of the ligand and together with all above mentioned factors affect the kinetics of interactions with biomolecules, and thus, also their biological activity [ 40 , 41 , 42 ]. Previously, we have already reported stability investigations of some organoruthenium(II)-pyrithionato complexes [ 22 , 24 , 32 ] as well as of structurally related organoruthenium(II) compounds [ 40 , 41 , 42 ] by NMR, MS, and UV-Vis spectroscopies. Firstly, we have shown by 1 H NMR that compound 1a is stable in DMSO-d 6 /D 2 O solvent system [ 22 ] and later also confirmed the stability of 1a complex in the D 2 O solution containing NaCl [ 24 ].…”

“…These molecules can, however, also react with metallodrugs possessing labile ligands [39]. In our previous studies, we have found that the behavior of the complexes depends on the type of the ligand and together with all above mentioned factors affect the kinetics of interactions with biomolecules, and thus, also their biological activity [40][41][42]. Previously, we have already reported stability investigations of some organoruthenium(II)-pyrithionato complexes [22,24,32] as well as of structurally related organoruthenium(II) compounds [40][41][42] by NMR, MS, and UV-Vis spectroscopies.…”

“…An additional evidence was provided by electrospray ionization-mass spectrometry (ESI-MS), taking advantage by sensitivity and soft ionization method of this technique, which allows to reveal non-covalent interactions with an efficient detection across a range of solvents, which we have already reported in some similar systems for organoruthenium(II) compounds [41,42]. In detail, ESI-MS analysis was carried out in positive ion mode by direct infusion from an aqueous solution of 1b prepared immediately before measurement and after three days.…”

Organoruthenated Nitroxoline Derivatives Impair Tumor Cell Invasion through Inhibition of Cathepsin B Activity

“…25−27 In recent years, we have been intensely investigating the biological properties and anticancer potential of metal complexes of hydroxyquinolines. 28−34 For instance, we synthesized an organoruthenium complex (Figure 1; center bottom) of clioquinol ( cqH ) and showed that the complex ( Ru-cq ) exhibits selective toxicity toward leukemic cell lines through a caspase-dependent mechanism of cell death. 28 Moreover, we determined that the complex Ru-cq does not interact with DNA and shows proteasome-independent inhibition of the NFκB signaling pathway without affecting cell-cycle distribution.…”