Binding mechanisms of half-sandwich Rh(III) and Ru(II) arene complexes on human serum albumin: a comparative study

Abstract

Various half-sandwich ruthenium(II) arene complexes and rhodium(III) arene complexes have been intensively investigated due to their prominent anticancer activity. The interaction of the organometallic complexes of Ru(η 6 - p -cymene) and Rh(η 5 -C 5 Me 5 ) with human serum albumin (HSA) was studied in detail by a combination of various methods such as ultrafiltration, capillary electrophoresis, 1 H NMR spectroscopy, fluorometry and UV–visible spectrophotometry in the presence of 100 mM chloride ions. Binding characteristics of the organometallic ions and their complexes with deferiprone, 2-picolinic acid, maltol, 6-methyl-2-picolinic acid and 2-quinaldic acid were evaluated. Kinetic aspects and reversibility of the albumin binding are also discussed. The effect of low-molecular-mass blood components on the protein binding was studied in addition to the interaction of organorhodium complexes with cell culture medium components. The organometallic ions were found to bind to HSA to a high extent via a coordination bond. Release of the bound metal ions was kinetically hindered and could not be induced by the denaturation of the protein. Binding of the Ru(η 6 - p -cymene) triaqua cation was much slower (ca. 24 h) compared to the rhodium congener (few min), while their complexes interacted with the protein relatively fast (1–2 h). The studied complexes were bound to HSA coordinatively. The highly stable and kinetically inert 2-picolinate Ru(η 6 - p -cymene) complex bound in an associative manner preserving its original entity, while lower stability complexes decomposed partly or completely upon binding to HSA. Fast, non-specific and high-affinity binding of the complexes on HSA highlights their coordinative interaction with various types of proteins possibly decreasing effective drug concentration. Graphic abstract Electronic supplementary material The online version of this article (10.1007/s00775-019-01683-0) contains supplementary material, which is available to authorized users.

Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity

“…The long contact time that is necessary to attain equilibrium suggests that a covalent binding interaction is probably occurring—upon the exchange of one of the more labile ligands (such as chloride) in the RuNTF coordination sphere by a suitable donor from a protein residue. Since this Ru complex binds in very close vicinity of Trp214, the basic N imidazole of His242 is very probable and has been often proposed for other Ru complexes [41,48,49,55]. It is possible that a water molecule is also involved in the stabilization of RuNTF and binding within site I, as found for warfarin and for other molecules [41,56].…”

New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding

“…Site IB (located in Subdomain IB) has also been reported as a valid binding pocket for various pharmaceutical drugs and natural compounds. [ 67 ]…”

“…Site IB (located in Subdomain IB) has also been reported as a valid binding pocket for various pharmaceutical drugs and natural compounds. [67] The 2D docking of HSA with Ln(5-HOF)(o-phen) is presented in Figures 6, S41, and S42. Whereas Ln (5-HOF)(o-phen) are bound within Subdomain IB of F I G U R E 6 Docking simulation results showing the interaction of Sm(5-HOF)(o-phen) with transferrin (Tf) and human serum albumin (HSA) and the corresponding binding pockets; AutoDock 4.2.6 (in AutodockTools) software package was used for molecular docking, and the 3D interactions were generated in Discovery Studio 4.1.…”

Effect of the Additional Carboxyl Group in Half‐Sandwich Organometallic 2,4‐Dipicolinate Complexes on Solution Speciation and Structure

“…Reactivity of the Rh(η 5 -C 5 Me 5 ) and Ru(η 6 -p-cymene) complexes of 2,4-dipic and pic was also measured towards simple biomolecules, namely 1-methylimidazole and guanosine. Coordination of histidine imidazole nitrogen is suggested in the interaction of human serum albumin with half-sandwich organoruthenium complexes, [33,34] thus 1-methylimidazole, as a monodentate nitrogen donor ligand, can serve as a simplified binding model. While the N7 donor was reported to be the most powerful binding site for pseudo-octahedral Ru(η 6 -arene) complexes in case of guanosine.…”