{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:10Z","timestamp":1787029090492,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The binding ability of five bifunctional 3-hydroxy-4-pyridinones towards Cu2+ and Fe3+ was studied by means of potentiometric and UV\u2013Vis spectrophotometric measurements carried out at I = 0.15 mol L\u22121 in NaCl(aq),T = 298.15 K and 310.15 K. The data treatments allowed us to determine speciation schemes featured by metal-ligand species with different stoichiometry and stability, owing to the various functional groups present in the 3-hydroxy-4-pyridinones structures, which could potentially participate in the metal complexation, and in the Cu2+ and Fe3+ behaviour in aqueous solution. Furthermore, the sequestering ability and metal chelating affinity of the ligands were investigated by the determination of pL0.5 and pM parameters at different pH conditions. Finally, a comparison between the Cu2+ and Fe3+\/3-hydroxy-4-pyridinones data herein presented with those already reported in the literature on the interaction of Zn2+ and Al3+ with the same ligands showed that, from the thermodynamic point of view, the 3-hydroxy-4-pyridinones are particularly selective towards Fe3+ and could therefore be considered promising iron-chelating agents, also avoiding the possibility of competition, and eventually the depletion, of essential metal cations of biological and environmental relevance, such as Cu2+ and Zn2+.<\/jats:p>","DOI":"10.3390\/molecules26237280","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T22:01:11Z","timestamp":1638309671000},"page":"7280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bifunctional 3-Hydroxy-4-Pyridinones as Potential Selective Iron(III) Chelators: Solution Studies and Comparison with Other Metals of Biological and Environmental Relevance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-2897","authenticated-orcid":false,"given":"Anna","family":"Irto","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Universit\u00e0 di Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1380-5380","authenticated-orcid":false,"given":"Paola","family":"Cardiano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Universit\u00e0 di Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-4392","authenticated-orcid":false,"given":"Karam","family":"Chand","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rov\u00edsco Pais 1, 1049-001 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia Maria","family":"Cigala","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Universit\u00e0 di Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9143-9582","authenticated-orcid":false,"given":"Francesco","family":"Crea","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Universit\u00e0 di Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-2827","authenticated-orcid":false,"given":"Concetta","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Universit\u00e0 di Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-9368","authenticated-orcid":false,"given":"Maria Am\u00e9lia","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rov\u00edsco Pais 1, 1049-001 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"ref_1","first-page":"221","article-title":"Roles of metals in human health","volume":"2","author":"Gupta","year":"2018","journal-title":"MOJ Biorg. Org. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Luch, A. (2012). Heavy Metals Toxicity and the Environment. Molecular, Clinical and Environmental Toxicology, Springer.","DOI":"10.1007\/978-3-7643-8340-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ccr.2011.08.008","article-title":"Hydroxypyridinones as \u201cprivileged\u201d chelating structures for the design of medicinal drugs","volume":"256","author":"Santos","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1071\/FP08288","article-title":"Copper in plants: Acquisition, transport and interactions","volume":"36","author":"Yruela","year":"2009","journal-title":"Funct. Plant Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1051\/agro:2001105","article-title":"Aluminum toxicity in plants: A review","volume":"21","author":"Rout","year":"2001","journal-title":"Agronomie"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hochmuth, G. (2021, November 09). Iron (Fe) Nutrition of Plants: University of Florida. IFAS Extension. SL353\/SS555, 8\/EDIS 2011, 2011, 8. Available online: https:\/\/edis.ifas.ufl.edu\/pdf\/SS\/SS55500.pdf.","DOI":"10.32473\/edis-ss555-2011"},{"key":"ref_7","first-page":"881","article-title":"Iron in the environment","volume":"33","author":"Kamble","year":"2013","journal-title":"Indian J. Environ. Prot."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Merian, E., Anke, M., Ihnat, M., and Stoeppler, M. (2004). Elements and Their Compounds in the Environment, Wiley. [2nd ed.].","DOI":"10.1002\/9783527619634"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2002-3-8-reviews1024","article-title":"Iron stress in plants","volume":"3","author":"Connolly","year":"2002","journal-title":"Genome Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100008","DOI":"10.1016\/j.stress.2021.100008","article-title":"Iron homeostasis in plants and its crosstalk with copper, zinc, and manganese","volume":"1","author":"Rai","year":"2021","journal-title":"Plant Stress"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114349","DOI":"10.1016\/j.molliq.2020.114349","article-title":"Complexation of environmentally and biologically relevant metals with bifunctional 3-hydroxy-4-pyridinones","volume":"319","author":"Irto","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_12","unstructured":"Reedijk, J., and Poeppelmeier, K. (2013). 3.35-Chelation Therapy. Comprehensive Inorganic Chemistry II, Elsevier. [2nd ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jinorgbio.2018.05.017","article-title":"Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: Synthesis, solution equilibrium studies and in vivo evaluation","volume":"186","author":"Irto","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.4081\/thal.2014.2046","article-title":"Iron chelating agents for iron overload diseases","volume":"4","author":"Crisponi","year":"2014","journal-title":"Thalass. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.molliq.2018.09.107","article-title":"New bis-(3-hydroxy-4-pyridinone)-NTA-derivative: Synthesis, binding ability towards Ca2+, Cu2+, Zn2+, Al3+, Fe3+ and biological assays","volume":"272","author":"Irto","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_16","unstructured":"Hider, R.C., Kontoghiorghes, G., Silver, J., and Stockham, M.A. (1982). (UK Pattent 2117766)."},{"key":"ref_17","first-page":"2106","article-title":"Deferiprone approved for iron overload","volume":"68","author":"Traynor","year":"2011","journal-title":"Am. J. Health. Syst. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molliq.2019.02.042","article-title":"A new bis-(3-hydroxy-4-pyridinone)-DTPA-derivative: Synthesis, complexation of di-\/tri-valent metal cations and in vivo M3+ sequestering ability","volume":"281","author":"Irto","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Irto, A., Cardiano, P., Cataldo, S., Chand, K., Cigala, R.M., Crea, F., De Stefano, C., Gattuso, G., Muratore, N., and Pettignano, A. (2019). Speciation Studies of Bifunctional 3-Hydroxy-4-Pyridinone Ligands in the Presence of Zn2+ at Different Ionic Strengths and Temperatures. Molecules, 24.","DOI":"10.3390\/molecules24224084"},{"key":"ref_20","unstructured":"Baes, C.F., and Mesmer, R.E. (1976). The Hydrolysis of Cations, John Wyley & Sons."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1016\/S0016-7037(99)00270-7","article-title":"The solubility of iron hydroxide in sodium chloride solutions","volume":"63","author":"Liu","year":"1999","journal-title":"Geochim. Cosmochim. Acta"},{"key":"ref_22","unstructured":"Martell, A.E., Smith, R.M., and Motekaitis, R.J. (2004). NIST Critically Selected Stability Constants of Metal Complexes Database, 8."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1107\/S0567739476001551","article-title":"Revised Effective Ionic Radii and Systematic Studies of Interatomic Distances in Halides and Chalcogenides","volume":"A32","author":"Shannon","year":"1976","journal-title":"Acta Crystallogr."},{"key":"ref_24","unstructured":"May, E.F., May, P.M., Murray, K., and Darren, R. (2019). Joint Expert Speciation System, JESS Primer. Available online: http:\/\/jess.murdoch.edu.au\/docs\/Jess_Primer_V86.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jinorgbio.2019.02.006","article-title":"Complex formation equilibria of polyamine ligands with copper(II) and zinc(II)","volume":"194","author":"Nurchi","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6215","DOI":"10.1021\/ja01653a001","article-title":"Metal-Amine Co\u00f6rdination Compounds. I. Copper(II) Complexes","volume":"76","author":"Pflaum","year":"1954","journal-title":"J. Am. Chem. Soc."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1021\/ed045p581","article-title":"Hard and soft acids and bases, HSAB, part 1: Fundamental principles, part II: Underlying theories","volume":"45","author":"Pearson","year":"1968","journal-title":"J. Chem. Educ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/ed045p643","article-title":"Hard and soft acids and bases, HSAB, part II: Underlying theories","volume":"45","author":"Pearson","year":"1968","journal-title":"J. Chem. Educ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0010-8545(98)00260-4","article-title":"Hyperquad simulation and speciation (HySS): A utility program for the investigation of equilibria involving soluble and partially soluble species","volume":"184","author":"Alderighi","year":"1999","journal-title":"Coord. Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00775-005-0003-7","article-title":"Bifunctional 3-hydroxy-4-pyridinone derivatives as potential pharmaceuticals: Synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation with 67Ga","volume":"10","author":"Santos","year":"2005","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0162-0134(02)00483-X","article-title":"N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: Synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation","volume":"92","author":"Santos","year":"2002","journal-title":"J. Inorg. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0020-1693(00)80327-8","article-title":"Stabilities of 1,2-dimethyl-3-hydroxy-4-pyridinone chelates of divalent and trivalent metal ions","volume":"191","author":"Clarke","year":"1992","journal-title":"Inorg. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.jinorgbio.2007.10.012","article-title":"Potentiometric, spectrophotometric and calorimetric study on iron(III) and copper(II) complexes with 1,2-dimethyl-3-hydroxy-4-pyridinone","volume":"102","author":"Nurchi","year":"2008","journal-title":"J. Inorg. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1016\/S0277-5387(02)01239-1","article-title":"A new bipodal carboxy-bis(hydroxypyridinonate) ligand.: Synthesis and complexation with copper(II), nickel(II) and zinc(II) in aqueous solution","volume":"21","author":"Santos","year":"2002","journal-title":"Polyhedron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0020-1693(00)82997-7","article-title":"Stabilities of the iron(III) chelates of 1,2-dimethyl-3-hydroxy-4-pyridinone and related ligands","volume":"183","author":"Motekaitis","year":"1991","journal-title":"Inorg. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Perrin, D.D. (1958). The stability of complexes of ferric ion and amino-acids. J. Chem. Soc., 3125\u20133128.","DOI":"10.1039\/jr9580003125"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1021\/ic00200a030","article-title":"Ferric ion sequestering agents. Synthesis, structures, and thermodynamics of complexation of cobalt(III) and iron(III) tris complexes of several chelating hydroxypyridinones","volume":"24","author":"Scarrow","year":"1985","journal-title":"Inorg. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1021\/jm9707784","article-title":"Synthesis, Physicochemical Properties, and Evaluation of N-Substituted-2-alkyl-3-hydroxy-4(1H)-pyridinones","volume":"41","author":"Rai","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.2174\/0929867321666140601160740","article-title":"Chelating agents for the sequestration of mercury(II) and monomethyl mercury(II)","volume":"21","author":"Crea","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1021\/ar50137a004","article-title":"Coordination chemistry and microbial iron transport","volume":"12","author":"Raymond","year":"1979","journal-title":"Acc. Chem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/0022-1902(74)80741-4","article-title":"Complexes of adrenaline and related compounds with Ni2+, Cu2+, Zn2+, Cd2+ and Pb2+","volume":"36","author":"Simeon","year":"1974","journal-title":"J. Inorg. Nucl. Chem."},{"key":"ref_43","unstructured":"Flaschka, H.A. (1959). EDTA Titration, Pergamon Press."},{"key":"ref_44","first-page":"643","article-title":"Computer Analysis of Equilibrium Data in Solution. ESAB2M: An Improved Version of the ESAB Program","volume":"7","author":"Princi","year":"1987","journal-title":"Ann. Chim."},{"key":"ref_45","first-page":"257","article-title":"Binding of Tripolyphosphate by Aliphatic Amines: Formation, Stability and Calculation Problems","volume":"86","author":"Foti","year":"1996","journal-title":"Ann. Chim."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/0039-9140(96)01958-3","article-title":"Investigation of equilibria in solution. Determination of equilibrium constants with the HYPERQUAD suite programs","volume":"43","author":"Gans","year":"1996","journal-title":"Talanta"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/23\/7280\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:07Z","timestamp":1760168287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/23\/7280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,30]]},"references-count":46,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["molecules26237280"],"URL":"https:\/\/doi.org\/10.3390\/molecules26237280","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,30]]}}}