{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:02:01Z","timestamp":1785452521526,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T00:00:00Z","timestamp":1674259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The [N,N\u2032-disalicylidene-1,2-phenylenediamine]iron(III) ([salophene]iron(III)) derivatives 1\u20134 with anionic axial ligands (A = Cl\u2212, NO3\u2212, SCN\u2212, CH3COO\u2212) and complexes 5 and 6 with neutral ligands (A = imidazole, 1-methylimidazole) as well as the \u03bc-oxo dimer 7 inhibited proliferation, reduced metabolic activity, and increased mitochondrial reactive oxygen species. Ferroptosis as part of the mode of action was identified by inhibitor experiments, together with induction of lipid peroxidation and diminished mitochondrial membrane potential. No differences in activity were observed for all compounds except 4, which was slightly less active. Electrochemical analyses revealed for all compounds a fast attachment of the solvent dimethyl sulfoxide and a release of the axial ligand A. In contrast, in dichloromethane and acetonitrile, ligand exchange did not take place, as analyzed by measurements of the standard potential for the iron(III\/II) redox reaction.<\/jats:p>","DOI":"10.3390\/ijms24032173","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigations on the Influence of the Axial Ligand in [Salophene]iron(III) Complexes on Biological Activity and Redox Behavior"],"prefix":"10.3390","volume":"24","author":[{"given":"Hubert","family":"Descher","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie Luise","family":"Strich","sequence":"additional","affiliation":[{"name":"Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria"},{"name":"Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Enoh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-2664","authenticated-orcid":false,"given":"Brigitte","family":"Kircher","sequence":"additional","affiliation":[{"name":"Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria"},{"name":"Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-4012","authenticated-orcid":false,"given":"Ronald","family":"Gust","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S1381-1169(96)00299-3","article-title":"How do electronegative substituents make metal complexes better catalysts for the oxidation of hydrocarbons by dioxygen?","volume":"117","author":"Birnbaum","year":"1997","journal-title":"J. Mol. Catal. A Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/1087057110385227","article-title":"Fe(III)-salen and salphen complexes induce caspase activation and apoptosis in human cells","volume":"16","author":"Ansari","year":"2010","journal-title":"J. Biomol. Screen."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/jm500986h","article-title":"Fluorinated Fe(III) salophene complexes: Optimization of tumor cell specific activity and utilization of fluorine labeling for in vitro analysis","volume":"58","author":"Follia","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jinorgbio.2014.10.002","article-title":"Iron-salophen complexes involving azole-derived ligands: A new group of compounds with high-level and broad-spectrum in vitro antitumor activity","volume":"142","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1021\/acs.jmedchem.9b00814","article-title":"A new approach in cancer treatment: Discovery of chlorido[N,N-disalicylidene-1,2-phenylenediamine]iron(III) complexes as ferroptosis inducers","volume":"62","author":"Sagasser","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1039\/D0DT00168F","article-title":"Amide and ester derivatives of chlorido[4-carboxy-1,2-disalicylideneaminobenzene]iron(III) as necroptosis and ferroptosis inducers","volume":"49","author":"Baecker","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00775-009-0485-9","article-title":"[N,N-Bis(salicylidene)-1,2-phenylenediamine]metal complexes with cell death promoting properties","volume":"14","author":"Hille","year":"2009","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.leukres.2010.11.007","article-title":"[FeIII(salophene)Cl], a potent iron salophene complex overcomes multiple drug resistance in lymphoma and leukemia cells","volume":"35","author":"Lee","year":"2011","journal-title":"Leuk. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1089\/ars.2012.5014","article-title":"Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?","volume":"20","author":"Bystrom","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbrc.2016.10.086","article-title":"Lipid peroxidation in cell death","volume":"482","author":"Gaschler","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/BF01024073","article-title":"Catalytic decomposition of hydrogen peroxide in the presence of N, N-bis(salicylidene)-o-phenylenediamineiron(III) sorbed on to Dowex-50W resin","volume":"16","author":"Ashmawy","year":"1991","journal-title":"Transit. Met. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0022-0728(79)80081-9","article-title":"Electrochemistry of monomeric and oxo-bridged dimeric iron(III) complexes with the Schiff base ligand, N,N-ethylenebis(salicylidineimine)","volume":"101","author":"Wenk","year":"1979","journal-title":"J. Electroanal. Chem. Interfacial Electrochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0277-5387(00)84981-5","article-title":"Electrochemical studies of Iron(III) Schiff base complexes\u2014I. The monomeric FeIII(N2O2)Cl complexes","volume":"12","author":"Costes","year":"1993","journal-title":"Polyhedron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/0277-5387(94)00305-X","article-title":"Electrochemical studies of iron(III) Schiff base complexes\u2014II. Dimeric \u03bc-OXO[FeIII(N2O2)]2O complexes","volume":"14","author":"Costes","year":"1995","journal-title":"Polyhedron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11146","DOI":"10.1039\/c3dt50233c","article-title":"Comparison of chemical interactions with Li+ and catalytic reactivity of electrochemically generated [FeICl(L)]2\u2212 and [CoI(L)]\u2212 complexes (L = salen or salophen)","volume":"42","author":"Ueda","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ardp.201000237","article-title":"Effects of Metal Salophene and Saldach Complexes on Lymphoma and Leukemia Cells","volume":"344","author":"Hille","year":"2011","journal-title":"Arch. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1016\/j.ejmech.2010.08.037","article-title":"Influence of methoxy groups on the antiproliferative effects of [FeIII(salophene-OMe)Cl] complexes","volume":"45","author":"Hille","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1021\/ja00905a001","article-title":"Hard and Soft Acids and Bases","volume":"85","author":"Pearson","year":"1963","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5357","DOI":"10.1016\/S0040-4020(02)00481-7","article-title":"Non-symmetrical tetradentate vanadyl Schiff base complexes derived from 1,2-phenylene diamine and 1,3-naphthalene diamine as catalysts for the oxidation of cyclohexene","volume":"58","author":"Boghaei","year":"2002","journal-title":"Tetrahedron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ica.2018.12.002","article-title":"Studies on the stability of the anticancer-active [N,N-bis(salicylidene)-1,2-phenylenediamine]chloridoiron(III) complex under pharmacological-like conditions","volume":"487","author":"Ma","year":"2019","journal-title":"Inorg. Chim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1002\/jssc.201200734","article-title":"Development and validation of a LC method for the separation and determination of the anticancer-active Fe(III) (4-methoxy-salophene) using the new second-generation monolith","volume":"35","author":"Ma","year":"2012","journal-title":"J. Sep. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1134\/S2070205114050128","article-title":"Synthesis and characterization of iron oxide nanoparticles by solvothermal method","volume":"50","author":"Mishra","year":"2014","journal-title":"Prot. Met. Phys. Chem. Surf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8084","DOI":"10.1021\/ja00203a003","article-title":"Electronic and Raman spectroscopic properties of oxo-bridged dinuclear iron centers in proteins and model compounds","volume":"111","author":"Wheeler","year":"1989","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.poly.2012.08.085","article-title":"Syntheses, characterization and X-ray crystal structures of hexa-coordinated monomeric and oxo-bridged dimeric Fe(III) compounds with salen-type Schiff bases","volume":"48","author":"Jana","year":"2012","journal-title":"Polyhedron"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, H., Braun, A., Cramer, S.P., Gee, L.B., and Yoda, Y. (2021). Nuclear Resonance Vibrational Spectroscopy: A Modern Tool to Pinpoint Site-Specific Cooperative Processes. Crystals, 11.","DOI":"10.3390\/cryst11080909"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1000282","DOI":"10.4172\/2157-7064.1000282","article-title":"Spectroscopic Characterization of Disodium Hydrogen Orthophosphate and Sodium Nitrate after Biofield Treatment","volume":"6","author":"Trivedi","year":"2015","journal-title":"J. Chromatogr. Sep. Tech."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106689","DOI":"10.1016\/j.mineng.2020.106689","article-title":"A review of thiocyanate gold leaching\u2014Chemistry, thermodynamics, kinetics and processing","volume":"160","author":"Azizitorghabeh","year":"2021","journal-title":"Miner. Eng."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0022-2860(93)80113-A","article-title":"Vibrational spectroscopic studies of iron(II) acetate","volume":"296","author":"Edwards","year":"1993","journal-title":"J. Mol. Struct."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lange, T.S., Kim, K.K., Singh, R.K., Strongin, R.M., McCourt, C.K., and Brard, L. (2008). Iron(III)-salophene: An organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells. PLoS ONE, 3.","DOI":"10.1371\/annotation\/d97d24fc-aa07-40fd-88b2-6b2e050ddb31"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s000180300001","article-title":"Molecular mechanisms of N-acetylcysteine actions","volume":"60","author":"Zafarullah","year":"2003","journal-title":"Cell. Mol. Life Sci. CMLS"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:13:11Z","timestamp":1760119991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,21]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032173"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032173","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,21]]}}}