An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes
Authors
Mészáros, János P.Poljarević, Jelena
Szatmári, István
Csuvik, Oszkár
Fülöp, Ferenc
Szoboszlai, Norbert
Spengler, Gabriella
Enyedy, Éva A.
Article (Published version)
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Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η5-C5Me5)(H2O)3]2+, [Ru(η6-p-cymene)(H2O)3]2+and [Ru(η6-toluene)(H2O)3]2+were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and1H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log Dvalues (−0.8 to +0.4) at pH 7.4 at all tested Cl−concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pKavalues (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η6-arene) triaqua cations tha...n with [Rh(η5-C5Me5)(H2O)3]2+. Both the pKavalues and H2O/Cl−exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayedin vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η5-C5Me5) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration.
Source:
Dalton Transactions, 2020, 49, 23, 7977-7992Publisher:
- Royal Society of Chemistry
Funding / projects:
- GINOP-2.3.2-15-2016-00038
- FK 124240
- FIKP program TUDFO/47138-1/2019-ITM
- ÚNKP-19-3 National Excellence Program of the Ministry for Innovation and Technology
DOI: 10.1039/d0dt01256d
ISSN: 1477-9226
WoS: 000542720000034
Scopus: 2-s2.0-85086515473
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Mészáros, János P. AU - Poljarević, Jelena AU - Szatmári, István AU - Csuvik, Oszkár AU - Fülöp, Ferenc AU - Szoboszlai, Norbert AU - Spengler, Gabriella AU - Enyedy, Éva A. PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/4050 AB - Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η5-C5Me5)(H2O)3]2+, [Ru(η6-p-cymene)(H2O)3]2+and [Ru(η6-toluene)(H2O)3]2+were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and1H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log Dvalues (−0.8 to +0.4) at pH 7.4 at all tested Cl−concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pKavalues (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η6-arene) triaqua cations than with [Rh(η5-C5Me5)(H2O)3]2+. Both the pKavalues and H2O/Cl−exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayedin vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η5-C5Me5) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration. PB - Royal Society of Chemistry T2 - Dalton Transactions T1 - An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes VL - 49 IS - 23 SP - 7977 EP - 7992 DO - 10.1039/d0dt01256d ER -
@article{ author = "Mészáros, János P. and Poljarević, Jelena and Szatmári, István and Csuvik, Oszkár and Fülöp, Ferenc and Szoboszlai, Norbert and Spengler, Gabriella and Enyedy, Éva A.", year = "2020", abstract = "Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η5-C5Me5)(H2O)3]2+, [Ru(η6-p-cymene)(H2O)3]2+and [Ru(η6-toluene)(H2O)3]2+were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and1H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log Dvalues (−0.8 to +0.4) at pH 7.4 at all tested Cl−concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pKavalues (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η6-arene) triaqua cations than with [Rh(η5-C5Me5)(H2O)3]2+. Both the pKavalues and H2O/Cl−exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayedin vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η5-C5Me5) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration.", publisher = "Royal Society of Chemistry", journal = "Dalton Transactions", title = "An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes", volume = "49", number = "23", pages = "7977-7992", doi = "10.1039/d0dt01256d" }
Mészáros, J. P., Poljarević, J., Szatmári, I., Csuvik, O., Fülöp, F., Szoboszlai, N., Spengler, G.,& Enyedy, É. A.. (2020). An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes. in Dalton Transactions Royal Society of Chemistry., 49(23), 7977-7992. https://doi.org/10.1039/d0dt01256d
Mészáros JP, Poljarević J, Szatmári I, Csuvik O, Fülöp F, Szoboszlai N, Spengler G, Enyedy ÉA. An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes. in Dalton Transactions. 2020;49(23):7977-7992. doi:10.1039/d0dt01256d .
Mészáros, János P., Poljarević, Jelena, Szatmári, István, Csuvik, Oszkár, Fülöp, Ferenc, Szoboszlai, Norbert, Spengler, Gabriella, Enyedy, Éva A., "An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes" in Dalton Transactions, 49, no. 23 (2020):7977-7992, https://doi.org/10.1039/d0dt01256d . .