Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity
Five-coordinate Cu(II) complexes, [Cu(L<sup>n</sup>)X]ClO<sub>4</sub>/PF<sub>6</sub>, where L<sup>n</sup> = piperazine ligands bearing two pyridyl arms and X = ClO<sub>4</sub><sup>−</sup> for L<sup>n</sup> = L<sup...
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MDPI AG
2021-02-01
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| Series: | Inorganics |
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| Online Access: | https://www.mdpi.com/2304-6740/9/2/12 |
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| author | Sebastian Doniz Kettenmann Yvonne Nossol Febee R. Louka Julia R. Legrande Elise Marine Roland C. Fischer Franz A. Mautner Vinja Hergl Nora Kulak Salah S. Massoud |
| author_facet | Sebastian Doniz Kettenmann Yvonne Nossol Febee R. Louka Julia R. Legrande Elise Marine Roland C. Fischer Franz A. Mautner Vinja Hergl Nora Kulak Salah S. Massoud |
| author_sort | Sebastian Doniz Kettenmann |
| collection | DOAJ |
| description | Five-coordinate Cu(II) complexes, [Cu(L<sup>n</sup>)X]ClO<sub>4</sub>/PF<sub>6</sub>, where L<sup>n</sup> = piperazine ligands bearing two pyridyl arms and X = ClO<sub>4</sub><sup>−</sup> for L<sup>n</sup> = L<sup>1</sup> (<b>1-ClO<sub>4</sub></b>), L<sup>2</sup> (<b>2-ClO<sub>4</sub></b>), L<sup>3</sup> (<b>3-ClO<sub>4</sub></b>), and L<sup>6</sup> (<b>6-ClO<sub>4</sub></b>) as well as [Cu(L<sup>n</sup>)Cl]PF<sub>6</sub> for L<sup>n</sup> = L<sup>1</sup> (<b>1-Cl</b>), L<sup>4</sup> (<b>4-Cl</b>), and L<sup>5</sup> (<b>5-Cl</b>) 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(L<sup>n</sup>)(H<sub>2</sub>O)]<sup>2+</sup> 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: <b>1-Cl</b> ≈ <b>1-ClO<sub>4</sub></b> > <b>3-ClO<sub>4</sub></b> ≥ <b>2-ClO<sub>4</sub></b> with cleavage enhancements of up to 23 million. Complexes <b>4-Cl</b>, <b>5-Cl</b>, and <b>6-ClO<sub>4</sub></b> 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 <b>1-Cl</b>/<b>1-ClO<sub>4</sub></b>, DNA cleavage by <b>2-ClO<sub>4</sub></b> and <b>3-ClO<sub>4</sub></b> predominantly proceeds via a hydrolytic mechanism. Complexes <b>1-ClO<sub>4</sub></b>, <b>3-ClO<sub>4</sub></b>, and <b>5-Cl</b> were found to be cytotoxic against A2780 cells (IC<sub>50</sub> 30–40 µM). In fibroblasts, the IC<sub>50</sub> value was much higher for <b>3-ClO<sub>4</sub></b> with no toxic effect. |
| first_indexed | 2024-03-09T06:16:33Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2304-6740 |
| language | English |
| last_indexed | 2024-03-09T06:16:33Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Inorganics |
| spelling | doaj.art-5d92d2ca283a4da7bc23053f651fce482023-12-03T11:52:37ZengMDPI AGInorganics2304-67402021-02-01921210.3390/inorganics9020012Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and CytotoxicitySebastian Doniz Kettenmann0Yvonne Nossol1Febee R. Louka2Julia R. Legrande3Elise Marine4Roland C. Fischer5Franz A. Mautner6Vinja Hergl7Nora Kulak8Salah S. Massoud9Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, GermanyDepartment of Chemistry, University of Louisiana at Lafayette, P.O. Box 44370, Lafayette, LA 70504, USADepartment of Chemistry, University of Louisiana at Lafayette, P.O. Box 44370, Lafayette, LA 70504, USADepartment of Chemistry, University of Louisiana at Lafayette, P.O. Box 44370, Lafayette, LA 70504, USAInstitut für Anorganische Chemische, Technische Universität Graz, Stremayrgasse 9/V, A-8010 Graz, AustriaInstitut für Physikalische und Theoretische Chemie, Technische Universität Graz, Stremayrgasse 9/II, A-8010 Graz, AustriaInstitut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, GermanyDepartment of Chemistry, University of Louisiana at Lafayette, P.O. Box 44370, Lafayette, LA 70504, USAFive-coordinate Cu(II) complexes, [Cu(L<sup>n</sup>)X]ClO<sub>4</sub>/PF<sub>6</sub>, where L<sup>n</sup> = piperazine ligands bearing two pyridyl arms and X = ClO<sub>4</sub><sup>−</sup> for L<sup>n</sup> = L<sup>1</sup> (<b>1-ClO<sub>4</sub></b>), L<sup>2</sup> (<b>2-ClO<sub>4</sub></b>), L<sup>3</sup> (<b>3-ClO<sub>4</sub></b>), and L<sup>6</sup> (<b>6-ClO<sub>4</sub></b>) as well as [Cu(L<sup>n</sup>)Cl]PF<sub>6</sub> for L<sup>n</sup> = L<sup>1</sup> (<b>1-Cl</b>), L<sup>4</sup> (<b>4-Cl</b>), and L<sup>5</sup> (<b>5-Cl</b>) 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(L<sup>n</sup>)(H<sub>2</sub>O)]<sup>2+</sup> 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: <b>1-Cl</b> ≈ <b>1-ClO<sub>4</sub></b> > <b>3-ClO<sub>4</sub></b> ≥ <b>2-ClO<sub>4</sub></b> with cleavage enhancements of up to 23 million. Complexes <b>4-Cl</b>, <b>5-Cl</b>, and <b>6-ClO<sub>4</sub></b> 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 <b>1-Cl</b>/<b>1-ClO<sub>4</sub></b>, DNA cleavage by <b>2-ClO<sub>4</sub></b> and <b>3-ClO<sub>4</sub></b> predominantly proceeds via a hydrolytic mechanism. Complexes <b>1-ClO<sub>4</sub></b>, <b>3-ClO<sub>4</sub></b>, and <b>5-Cl</b> were found to be cytotoxic against A2780 cells (IC<sub>50</sub> 30–40 µM). In fibroblasts, the IC<sub>50</sub> value was much higher for <b>3-ClO<sub>4</sub></b> with no toxic effect.https://www.mdpi.com/2304-6740/9/2/12copperDNA cleavagephosphodiestercytotoxicitypiperazine |
| spellingShingle | Sebastian Doniz Kettenmann Yvonne Nossol Febee R. Louka Julia R. Legrande Elise Marine Roland C. Fischer Franz A. Mautner Vinja Hergl Nora Kulak Salah S. Massoud Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity Inorganics copper DNA cleavage phosphodiester cytotoxicity piperazine |
| title | Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity |
| title_full | Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity |
| title_fullStr | Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity |
| title_full_unstemmed | Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity |
| title_short | Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity |
| title_sort | copper ii complexes with tetradentate piperazine based ligands dna cleavage and cytotoxicity |
| topic | copper DNA cleavage phosphodiester cytotoxicity piperazine |
| url | https://www.mdpi.com/2304-6740/9/2/12 |
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