Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 23, 2020
Previous Article Next Article

An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes

Author affiliations

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 and 1H 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 D values (−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 pKa values (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 pKa values 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 assayed in 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.

Graphical abstract: An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes

Back to tab navigation

Supplementary files

Article information


Submitted
04 Apr 2020
Accepted
14 May 2020
First published
14 May 2020

This article is Open Access

Dalton Trans., 2020,49, 7977-7992
Article type
Paper

An 8-hydroxyquinoline–proline hybrid with multidrug resistance reversal activity and the solution chemistry of its half-sandwich organometallic Ru and Rh complexes

J. P. Mészáros, J. M. Poljarević, I. Szatmári, O. Csuvik, F. Fülöp, N. Szoboszlai, G. Spengler and É. A. Enyedy, Dalton Trans., 2020, 49, 7977
DOI: 10.1039/D0DT01256D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements