Abstract:Please cite this article as: J.P. Mészáros, J.M. Poljarevic, G.T. Gál, et al., Comparative solution and structural studies of half-sandwich rhodium and ruthenium complexes bearing curcumin and acetylacetone, Journal of Inorganic Biochemistry, https://doi.ABSTRACT Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds. Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh( 5 -C5Me5)(H2O)3] 2+ . Acetylacetone (H… Show more
“…The original RhCp*(dhp) complex is completely dissociated, dhp and (most probably) coordinating water as well are replaced by RPMI 1640 components, which results in the appearance of the same peak set for C 5 Me 5 methyl protons like in case of RhCp* itself, and no mixed-ligand complex formation can be observed. A similar result was obtained with related complex RhCp*(acetylacetonato) in our former work [65]. The pic complex reacts somewhat differently: about 75% of the ligand is liberated here as well, but the rest is coordinated to the metal ion.…”
Section: Resultssupporting
confidence: 87%
“…In cytotoxicity measurements, the tested compounds are dissolved typically in micromolar concentrations in cell medium, and more pronounced decomposition of the original complexes is expected under these conditions. Consequently, cytotoxicity measured for lower stability complexes (e.g., the dhp or acac complexes) did not exceed the sum of efficacy measured for organorhodium ion (coordinated to medium components) and the ligand (if it is active) separately [56, 65]. Fig.…”
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.
“…The original RhCp*(dhp) complex is completely dissociated, dhp and (most probably) coordinating water as well are replaced by RPMI 1640 components, which results in the appearance of the same peak set for C 5 Me 5 methyl protons like in case of RhCp* itself, and no mixed-ligand complex formation can be observed. A similar result was obtained with related complex RhCp*(acetylacetonato) in our former work [65]. The pic complex reacts somewhat differently: about 75% of the ligand is liberated here as well, but the rest is coordinated to the metal ion.…”
Section: Resultssupporting
confidence: 87%
“…In cytotoxicity measurements, the tested compounds are dissolved typically in micromolar concentrations in cell medium, and more pronounced decomposition of the original complexes is expected under these conditions. Consequently, cytotoxicity measured for lower stability complexes (e.g., the dhp or acac complexes) did not exceed the sum of efficacy measured for organorhodium ion (coordinated to medium components) and the ligand (if it is active) separately [56, 65]. Fig.…”
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.
“…The stability constant is the highest for Ru(η 6 -p-cymene) complexes, which is followed by Ru(η 6 -toluene) and the Rh(η 5 -C 5 Me 5 ) complexes have the lowest stability constants ( Table 3). The same tendency has been found previously in the case of other (O,O) donor bidentate ligands [33]. Based on the determined stability constants ( Table 3) (Fig.…”
Section: Complex Formation Equilibria Of Naphthoquinones With Organomsupporting
confidence: 87%
“…Based on the crystallographic structures and literature data of other half-sandwich Ru(II) and Rh(III) complexes with (O,O) donors, mono complex formation is the most probable process under the applied conditions. The complexes of half-sandwich Rh and Ru complexes with (O,O) donors usually reaches the equilibrium state rather fast [28,[32][33][34]. Because of the extended delocalized electron system, the complexes of phthiocol and lawsone have absorbance in the UV-Vis region, so spectrophotometric titration is a suitable method for following the complex formation and spectra were recorded at 1:1 and 1:2 metal-to-ligand ratios.…”
Section: Complex Formation Equilibria Of Naphthoquinones With Organommentioning
confidence: 99%
“…1,2-dimethyl-3-hydroxy-pyridin-4(1H)-one (deferiprone) [28,[32][33][34]. The stability constants for the Ru(η 6 -toluene) -deferiprone system were missing for this comparison, thus pH-potentiometric titrations were performed in this work to determine these data, which are: log K [M(arene)L] = 11.74 ± 0.08 and pK a [M(arene)L] = 9.34 ± 0.09.…”
Section: Comparison the Stability Of Naphthoquinone Complexes With Otmentioning
Half-sandwich organometallic complexes featuring Ru(II), Os(II) and Rh(III) metal centers and naturally occurring bidentate 2-hydroxy-[1,4]-naphthoquinone ligands (lawsone and phthiocol) have been synthesized and characterized in both solid state and solution phase by analytical, spectroscopic, electrochemical and single crystal X-ray diffraction techniques. Comparative studies revealed the influence of the respective metal center (Ru, Os, Rh), leaving group (Cl, Br, I) and arene (p-cymene, toluene, pentamethylcyclopentadienyl), as well as the naphthoquinone ligand on the structural properties and solution speciation. Additionally, cytotoxicity was tested in SW480, CH1/PA-1 and A549 human cancer cell lines showing a broad range of IC 50 values.
We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [CpXRh(C^N)Z]0/+, in which CpX = Cp*, Cpph, or Cpbiph, C^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X‐ray crystal structures showing the expected “piano‐stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9‐ethyl guanine or glutathione compared to their pyridine analogues. The 1‐biphenyl‐2,3,4,5‐tetramethylcyclopentadienyl complex [CpbiphRh(benzo‐[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD+ and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [CpbiphRh(benzo[h]quinoline)py]+ (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5‐fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand‐controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.
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