Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex

A novel ruthenium(II) complex, [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] (<b>1</b>), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations support...

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Main Authors: Stefan Perendija, Dušan Dimić, Thomas Eichhorn, Aleksandra Rakić, Luciano Saso, Đura Nakarada, Dragoslava Đikić, Teodora Dragojević, Jasmina Dimitrić Marković, Goran N. Kaluđerović
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Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/15/3088
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author Stefan Perendija
Dušan Dimić
Thomas Eichhorn
Aleksandra Rakić
Luciano Saso
Đura Nakarada
Dragoslava Đikić
Teodora Dragojević
Jasmina Dimitrić Marković
Goran N. Kaluđerović
author_facet Stefan Perendija
Dušan Dimić
Thomas Eichhorn
Aleksandra Rakić
Luciano Saso
Đura Nakarada
Dragoslava Đikić
Teodora Dragojević
Jasmina Dimitrić Marković
Goran N. Kaluđerović
author_sort Stefan Perendija
collection DOAJ
description A novel ruthenium(II) complex, [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] (<b>1</b>), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex <b>1</b> with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol<sup>−1</sup>. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of <b>1</b> as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors.
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spelling doaj-art-12dab66d53fb447cbb57a94deea6d36a2025-08-20T03:36:36ZengMDPI AGMolecules1420-30492025-07-013015308810.3390/molecules30153088Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] ComplexStefan Perendija0Dušan Dimić1Thomas Eichhorn2Aleksandra Rakić3Luciano Saso4Đura Nakarada5Dragoslava Đikić6Teodora Dragojević7Jasmina Dimitrić Marković8Goran N. Kaluđerović9Faculty of Physical Chemistry, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Physical Chemistry, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Engineering and Natural Sciences, University of Applied Sciences Merseburg, D-06217 Merseburg, GermanyFaculty of Physical Chemistry, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyFaculty of Physical Chemistry, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Physical Chemistry, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Engineering and Natural Sciences, University of Applied Sciences Merseburg, D-06217 Merseburg, GermanyA novel ruthenium(II) complex, [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] (<b>1</b>), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex <b>1</b> with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol<sup>−1</sup>. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of <b>1</b> as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors.https://www.mdpi.com/1420-3049/30/15/3088Ru(II) complexHSADNADFTEPRmolecular docking
spellingShingle Stefan Perendija
Dušan Dimić
Thomas Eichhorn
Aleksandra Rakić
Luciano Saso
Đura Nakarada
Dragoslava Đikić
Teodora Dragojević
Jasmina Dimitrić Marković
Goran N. Kaluđerović
Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
Molecules
Ru(II) complex
HSA
DNA
DFT
EPR
molecular docking
title Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
title_full Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
title_fullStr Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
title_full_unstemmed Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
title_short Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl<sub>2</sub>(η<sup>6</sup>-<i>p</i>-cymene)(bph-κ<i>N</i>)] Complex
title_sort synthesis characterization hsa dna binding and cytotoxic activity of rucl sub 2 sub η sup 6 sup i p i cymene bph κ i n i complex
topic Ru(II) complex
HSA
DNA
DFT
EPR
molecular docking
url https://www.mdpi.com/1420-3049/30/15/3088
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