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

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 ([Cu<sub>...

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Autores principales:	Nicolás Veiga, Natalia Alvarez, Eduardo E. Castellano, Javier Ellena, Gianella Facchin, María H. Torre
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antioxidant pro-oxidant copper complexes SOD-like activity TBARS X-ray diffraction Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/8756632964bd49de87cc4518d4c35341
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spelling	oai:doaj.org-article:8756632964bd49de87cc4518d4c353412021-11-11T18:30:47ZComparative 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 Compounds10.3390/molecules262165201420-3049https://doaj.org/article/8756632964bd49de87cc4518d4c353412021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6520https://doaj.org/toc/1420-3049In 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 ([Cu<sub>3</sub>(AlaLeu)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>(CO<sub>3</sub>)]·PF<sub>6</sub>·H<sub>2</sub>O), 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 H<sub>2</sub>O<sub>2</sub> produce oxidative damage to 2-deoxy-<span style="font-variant: small-caps;">d</span>-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–amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu–dipeptide–phen complexes are good SOD mimics but poor ROS producers. The activity of Cu–dipeptide 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.Nicolás VeigaNatalia AlvarezEduardo E. CastellanoJavier EllenaGianella FacchinMaría H. TorreMDPI AGarticleantioxidantpro-oxidantcopper complexesSOD-like activityTBARSX-ray diffractionOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6520, p 6520 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antioxidant pro-oxidant copper complexes SOD-like activity TBARS X-ray diffraction Organic chemistry QD241-441
spellingShingle	antioxidant pro-oxidant copper complexes SOD-like activity TBARS X-ray diffraction Organic chemistry QD241-441 Nicolás Veiga Natalia Alvarez Eduardo E. Castellano Javier Ellena Gianella Facchin María H. Torre 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
description	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 ([Cu<sub>3</sub>(AlaLeu)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>(CO<sub>3</sub>)]·PF<sub>6</sub>·H<sub>2</sub>O), 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 H<sub>2</sub>O<sub>2</sub> produce oxidative damage to 2-deoxy-<span style="font-variant: small-caps;">d</span>-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–amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu–dipeptide–phen complexes are good SOD mimics but poor ROS producers. The activity of Cu–dipeptide 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.
format	article
author	Nicolás Veiga Natalia Alvarez Eduardo E. Castellano Javier Ellena Gianella Facchin María H. Torre
author_facet	Nicolás Veiga Natalia Alvarez Eduardo E. Castellano Javier Ellena Gianella Facchin María H. Torre
author_sort	Nicolás Veiga
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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8756632964bd49de87cc4518d4c35341
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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

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