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Open AccessArticle

Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity

Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, Germany
Department of Chemistry, University of Louisiana at Lafayette, P.O. Box 44370, Lafayette, LA 70504, USA
Institut für Anorganische Chemische, Technische Universität Graz, Stremayrgasse 9/V, A-8010 Graz, Austria
Institut für Physikalische und Theoretische Chemie, Technische Universität Graz, Stremayrgasse 9/II, A-8010 Graz, Austria
Institut für Chemie, Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany
Department of Chemistry, Faculty of Science, Alexandria University, Moharem Bey, 21511 Alexandria, Egypt
Authors to whom correspondence should be addressed.
Received: 2 December 2020 / Revised: 27 December 2020 / Accepted: 29 December 2020 / Published: 1 February 2021
(This article belongs to the Special Issue Metal Complexes with Biological Functions)
Five-coordinate Cu(II) complexes, [Cu(Ln)X]ClO4/PF6, where Ln = piperazine ligands bearing two pyridyl arms and X = ClO4 for Ln = L1 (1-ClO4), L2 (2-ClO4), L3 (3-ClO4), and L6 (6-ClO4) as well as [Cu(Ln)Cl]PF6 for Ln = L1 (1-Cl), L4 (4-Cl), and L5 (5-Cl) have been synthesized and characterized by spectroscopic techniques. The molecular structures of the last two complexes were determined by X-ray crystallography. In aqueous acetonitrile solutions, molar conductivity measurements and UV-VIS spectrophotometric titrations of the complexes revealed the hydrolysis of the complexes to [Cu(Ln)(H2O)]2+ species. The biological activity of the Cu(II) complexes with respect to DNA cleavage and cytotoxicity was investigated. At micromolar concentration within 2 h and pH 7.4, DNA cleavage rate decreased in the order: 1-Cl1-ClO4 > 3-ClO42-ClO4 with cleavage enhancements of up to 23 million. Complexes 4-Cl, 5-Cl, and 6-ClO4 were inactive. In order to elucidate the cleavage mechanism, the cleavage of bis(4-nitrophenyl)phosphate (BNPP) and reactive oxygen species (ROS) quenching studies were conducted. The mechanistic pathway of DNA cleavage depends on the ligand’s skeleton: while an oxidative pathway was preferable for 1-Cl/1-ClO4, DNA cleavage by 2-ClO4 and 3-ClO4 predominantly proceeds via a hydrolytic mechanism. Complexes 1-ClO4, 3-ClO4, and 5-Cl were found to be cytotoxic against A2780 cells (IC50 30–40 µM). In fibroblasts, the IC50 value was much higher for 3-ClO4 with no toxic effect. View Full-Text
Keywords: copper; DNA cleavage; phosphodiester; cytotoxicity; piperazine copper; DNA cleavage; phosphodiester; cytotoxicity; piperazine
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MDPI and ACS Style

Doniz Kettenmann, S.; Nossol, Y.; Louka, F.R.; Legrande, J.R.; Marine, E.; Fischer, R.C.; Mautner, F.A.; Hergl, V.; Kulak, N.; Massoud, S.S. Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity. Inorganics 2021, 9, 12.

AMA Style

Doniz Kettenmann S, Nossol Y, Louka FR, Legrande JR, Marine E, Fischer RC, Mautner FA, Hergl V, Kulak N, Massoud SS. Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity. Inorganics. 2021; 9(2):12.

Chicago/Turabian Style

Doniz Kettenmann, Sebastian; Nossol, Yvonne; Louka, Febee R.; Legrande, Julia R.; Marine, Elise; Fischer, Roland C.; Mautner, Franz A.; Hergl, Vinja; Kulak, Nora; Massoud, Salah S. 2021. "Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity" Inorganics 9, no. 2: 12.

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