{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T23:43:54Z","timestamp":1783640634541,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:00:00Z","timestamp":1608940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The deanship of scientific research, king Abdulaziz University","award":["KEP-60-130-38"],"award-info":[{"award-number":["KEP-60-130-38"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ruthenium(II) arene complexes of the general formula [RuCl(\u03b76-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro\/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru\u2013Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.<\/jats:p>","DOI":"10.3390\/molecules26010076","type":"journal-article","created":{"date-parts":[[2020,12,27]],"date-time":"2020-12-27T20:04:58Z","timestamp":1609099498000},"page":"76","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-1368","authenticated-orcid":false,"given":"Mona S.","family":"Alsaeedi","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"},{"name":"Department of Chemistry, College of Science, Taif University, Al-Haweiah, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-263X","authenticated-orcid":false,"given":"Bandar A.","family":"Babgi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-4749","authenticated-orcid":false,"given":"Magda H.","family":"Abdellattif","sequence":"additional","affiliation":[{"name":"Chemistry Department, Deanship of Scientific Research, College of Sciences, Taif University, Al-Haweiah, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4070-3299","authenticated-orcid":false,"given":"Abdesslem","family":"Jedidi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4433-6783","authenticated-orcid":false,"given":"Mark G.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, Australian National University, Canberra ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-167X","authenticated-orcid":false,"given":"Mostafa A.","family":"Hussien","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Port Said University, Port Said 42521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1021\/cr980420v","article-title":"Current status of platinum-based antitumor drugs","volume":"99","author":"Wong","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2174\/092986706776872970","article-title":"Platinum Group Antitumor Chemistry: Design and Development of New Anticancer Drugs Complementary to Cisplatin","volume":"13","author":"Kettunen","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1039\/B715903J","article-title":"Towards the rational design of platinum(II) and gold(III) complexes as antitumour agents","volume":"12","author":"Wang","year":"2008","journal-title":"Dalton Trans."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctrv.2006.09.006","article-title":"Molecular mechanisms of resistance and toxicity associated with platinating agents","volume":"33","author":"Rabik","year":"2007","journal-title":"Cancer Treat. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2008.02.002","article-title":"Resistance against novel anticancer metal compounds: Differences and similarities","volume":"11","author":"Heffeter","year":"2008","journal-title":"Drug Resist. Updates"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1038\/s41467-018-06574-7","article-title":"A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemostherapy","volume":"9","author":"Yu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jab.2015.03.003","article-title":"Coordination compounds in cancer: Past, present and perspectives","volume":"13","author":"Trudu","year":"2015","journal-title":"J. Appl. Biomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.2174\/092986706776360941","article-title":"Ruthenium Complexes as Anticancer Agents","volume":"13","author":"Kostova","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/CAD.0b013e328322fbc5","article-title":"Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study","volume":"20","author":"Lentz","year":"2009","journal-title":"Anticancer Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ccr.2017.11.011","article-title":"Kinetically-inert polypyridylruthenium(II) complexes as therapeutic agents","volume":"375","author":"Li","year":"2017","journal-title":"Coord. Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jinorgbio.2017.07.010","article-title":"Characterizing activation mechanisms and binding preferences of ruthenium metallo-prodrugs by a competitive binding assay","volume":"177","author":"Artner","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/859730","article-title":"Anticancer Activities of Mononuclear Ruthenium(II) Coordination Complexes","volume":"2015","author":"Motswainyana","year":"2015","journal-title":"Adv. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jinorgbio.2016.02.018","article-title":"A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative -Anti-proliferative and anti-microbial activity","volume":"160","author":"Ude","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11770","DOI":"10.1021\/acs.inorgchem.6b01861","article-title":"Synthesis, structure, and anticancer activity of arene-ruthenium(II) complexes with acylpyrazolones bearing aliphatic groups in the acyl moiety","volume":"55","author":"Palmucci","year":"2016","journal-title":"Inorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vardhan, H., Nafady, A., Al-Enizi, A.M., Khandker, K., El-Sagher, H.M., Verma, G., Acevedo-Duncan, M., Alotaibi, T.M., and Ma, S. (2019). Investigation of the anticancer activity of coordination-driven self-assembled two-dimensional ruthenium metalla-rectangle. Molecules, 24.","DOI":"10.3390\/molecules24122284"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6587","DOI":"10.1021\/om800774t","article-title":"Water-soluble mixed-ligand ruthenium(II) and osmium(II) arene complexes with high antiproliferative activity","volume":"27","author":"Schuecker","year":"2008","journal-title":"Organometallics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1021\/acs.organomet.7b00875","article-title":"Half-Sandwich Arene Ruthenium(II) and Osmium(II) Thiosemicarbazone Complexes: Solution Behavior and Antiproliferative Activity","volume":"37","author":"Gatti","year":"2017","journal-title":"Organometallics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jinorgbio.2016.04.008","article-title":"How half sandwich ruthenium compounds interact with DNA while not being hydrolyzed; A comparative study","volume":"160","author":"Tsolis","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1021\/om1008132","article-title":"Ruthenium arene derivatives of chiral ferrocene-based P,N or P,O ligands. Transformation of chloro-alcohol into hydrido-carbonyl complexes","volume":"30","author":"Torres","year":"2011","journal-title":"Organometallics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1021\/acs.inorgchem.7b01959","article-title":"Half-Sandwich Iridium(III) and Ruthenium(II) Complexes Containing P^P-Chelating Ligands: A New Class of Potent Anticancer Agents with Unusual Redox Features","volume":"57","author":"Li","year":"2018","journal-title":"Inorg. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11274","DOI":"10.1021\/ic501865h","article-title":"Derivation of Structure\u2212Activity Relationships from the Anticancer Properties of Ruthenium(II) Arene Complexes with 2-Aryldiazole Ligands","volume":"53","author":"Rodriguez","year":"2014","journal-title":"Inorg. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13150","DOI":"10.1021\/acs.inorgchem.8b01270","article-title":"RuII(p-cymene) Compounds as Effective and Selective Anticancer Candidates with No Toxicity in Vivo","volume":"57","author":"Robalo","year":"2018","journal-title":"Inorg. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/anie.200462501","article-title":"Switching on a Signaling Pathway with an Organoruthenium Complex","volume":"44","author":"Williams","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10882","DOI":"10.1039\/b917792b","article-title":"Inert ruthenium half-sandwich complexes with anticancer activity","volume":"48","author":"Meggers","year":"2009","journal-title":"Dalton Trans."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1055\/s-2007-973893","article-title":"Exploring chemical space with organometallics: Ruthenium complexes as protein kinase inhibitors","volume":"8","author":"Meggers","year":"2007","journal-title":"Synlett"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1002\/anie.200503468","article-title":"Ruthenium half-sandwich complexes bound to protein kinase Pim-1","volume":"45","author":"Debreczeni","year":"2006","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1021\/ol0620646","article-title":"Ruthenium half-sandwich complexes as protein kinase inhibitors: An N-succinimidyl ester for rapid derivatizations of the cyclopentadienyl moiety","volume":"8","author":"Bregman","year":"2006","journal-title":"Org. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1021\/om101004z","article-title":"Ruthenium-and osmium-arene complexes of 2-substituted indolo[3,2- c ]quinolines: Synthesis, structure, spectroscopic properties, and antiproliferative activity","volume":"30","author":"Filak","year":"2011","journal-title":"Organometallics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9444","DOI":"10.1021\/ic9013366","article-title":"Ruthenium(II) Arene Anticancer Complexes with Redox-Active Diamine Ligands","volume":"48","author":"Bugarcic","year":"2009","journal-title":"Inorg. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1021\/om5011275","article-title":"Monomer-Dimer Divergent Behavior toward DNA in a Half Sandwich Ruthenium(II) Aqua Complex. Antiproliferative Biphasic Activity","volume":"34","author":"Busto","year":"2015","journal-title":"Organometallics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jinorgbio.2016.01.005","article-title":"Synthesis, characterization and biological evaluation of novel Ru(II)-arene complexes containing intercalating ligands","volume":"160","author":"Rangasamy","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.poly.2017.02.011","article-title":"Synthesis, structural analysis, redox properties and in vitro antitumor evaluation of half-sandwich complexes of Ru(II) with aminocoumarins","volume":"127","author":"Skoczynska","year":"2017","journal-title":"Polyhedron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/sj.bjc.6600290","article-title":"In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer","volume":"86","author":"Aird","year":"2002","journal-title":"Br. J. Cancer."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1021\/jm010051m","article-title":"Inhibition of cancer cell growth by ruthenium(II) arene complexes","volume":"44","author":"Morris","year":"2001","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/b135804","article-title":"Intercalation of organic dye molecules into double-stranded DNA\u2014General principles and recent developments","volume":"258","author":"Ihmels","year":"2005","journal-title":"Top. Curr. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1021\/ja017482e","article-title":"Organometallic ruthenium(II) diamine anticancer complexes: Arene-nucleobase stacking and stereospecific hydrogen-bonding in guanine adducts","volume":"124","author":"Chen","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","first-page":"21","article-title":"Activation mechanisms for organometallic anticancer complexes","volume":"32","author":"Pizarro","year":"2010","journal-title":"Top. Organomet. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14623","DOI":"10.1073\/pnas.2434016100","article-title":"Induced-fit recognition of DNA by organometallic complexes with dynamic stereogenic centers","volume":"100","author":"Chen","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16061","DOI":"10.1038\/nrdp.2016.61","article-title":"Ovarian cancer","volume":"2","author":"Matulonis","year":"2016","journal-title":"Nat. Rev. Disease Primers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1021\/jm060596m","article-title":"Structure-Activity Relationships for Cytotoxic Ruthenium (II) Arene Complexes Containing N,N-, N,O-, and O,O-Chelating Ligands","volume":"49","author":"Habtemariam","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s10895-017-2151-x","article-title":"Analytical Techniques Used to Detect DNA Binding Modes of Ruthenium(II) Complexes with Extended Phenanthroline Ring","volume":"27","author":"Devi","year":"2017","journal-title":"J. Fluoresc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1021\/acs.inorgchem.6b02419","article-title":"Copper(I)-phosphine polypyridyl complexes: Synthesis, characterization, DNA\/HAS binding study, and antiproliferative activity","volume":"56","author":"Villarreal","year":"2017","journal-title":"Inorg. Chem."},{"key":"ref_43","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09; Revision A.02, Gaussian, Inc."},{"key":"ref_44","unstructured":"Dennington, R., Keith, R.T., and Millam, J. (2009). GaussView. Version 5, Semichem. Inc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11623","DOI":"10.1021\/j100096a001","article-title":"Ab initio calculation of vibrational absorption and circular dichromism spectra using density functional force fields","volume":"98","author":"Stephens","year":"1994","journal-title":"J. Phys. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9342","DOI":"10.1021\/ja0630285","article-title":"Popular theoretical methods predict benzene and arenes to be nonplanar","volume":"128","author":"Moran","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1063\/1.456066","article-title":"Energy-adjusted ab initio pseudopotentials for the rare earth elements","volume":"90","author":"Dolg","year":"1989","journal-title":"J. Chem. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","author":"Grimme","year":"2010","journal-title":"J. Chem. Phys."},{"key":"ref_49","first-page":"337","article-title":"Antibacterial and antifungal activities of nine medicinal plants from Zaire","volume":"32","author":"Muanza","year":"1994","journal-title":"Pharm. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1021\/np50078a006","article-title":"DNA as an Affinity Probe Useful in the Detection and Isolation of Biologically Active Natural Products","volume":"54","author":"Pezzuto","year":"1991","journal-title":"J. Nat. Prod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. Nat. Cancer Inst."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/76\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:26Z","timestamp":1760179586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,26]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["molecules26010076"],"URL":"https:\/\/doi.org\/10.3390\/molecules26010076","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,26]]}}}