{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:44:20Z","timestamp":1785321860943,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"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>In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ([Cu3(AlaLeu)3(H2O)3(CO3)]\u00b7PF6\u00b7H2O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H2O2 produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine\/xanthine oxidase system. Our findings show that Cu\u2013amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu\u2013dipeptide\u2013phen complexes are good SOD mimics but poor ROS producers. The activity of Cu\u2013dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra.<\/jats:p>","DOI":"10.3390\/molecules26216520","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:51:36Z","timestamp":1635465096000},"page":"6520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8552-058X","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Veiga","sequence":"first","affiliation":[{"name":"Qu\u00edmica Inorg\u00e1nica, DEC, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Av. Gral. Flores 2124, Montevideo C.P. 11800, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6974-2569","authenticated-orcid":false,"given":"Natalia","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Qu\u00edmica Inorg\u00e1nica, DEC, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Av. Gral. Flores 2124, Montevideo C.P. 11800, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0499-8907","authenticated-orcid":false,"given":"Eduardo E.","family":"Castellano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Cristalografia Estrutural, Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos CEP 13566-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Ellena","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Multiusu\u00e1rio de Cristalografia Estrutural, Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos CEP 13566-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianella","family":"Facchin","sequence":"additional","affiliation":[{"name":"Qu\u00edmica Inorg\u00e1nica, DEC, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Av. 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