Editorial Board Members’ Collection Series in “Bioinorganic Chemistry of Copper”

A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 21993

Special Issue Editors


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Guest Editor
Laboratoire de Chimie de Coordination (LCC), CNRS UPR 8241, 205 Route de Narbonne, CEDEX 09, 31062 Toulouse, France
Interests: bio-inorganic chemistry; metal-peptide interactions; metals as therapeutic targets; inorganic compounds as therapeutic agents; amyloid-forming peptides; EPR spectroscopy; electrochemistry
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, Sao Paulo 05508-000, Brazil
Interests: metal complexes; DNA interactions; protein inhibition; ROS (Reactive Oxygen Species); anticancer metallodrugs; EPR spectroscopy

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Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay
Interests: coordination chemistry; medicinal inorganic chemistry; copper diimine complexes; cytotoxic activity; DNA interaction; gallium complexes

Special Issue Information

Dear Colleagues,

Copper is a transition element that is frequently found at the active site of proteins. Copper proteins are involved in a wide range of biological oxidation–reduction processes, which include long-range electron transfer, dismutation of superoxide, reduction of nitrite and nitrous oxide, and reversible binding, transport, activation, and two- or four-electron reduction of dioxygen to peroxide or water that are coupled to substrate oxidation or proton pumping. This diversity can be attributed to the unique geometric and electronic structures of the copper active sites that are intricately tailored for their specific functions. When these highly defined binding sites are not reached, then copper ions become toxic, as in the case of neurodegenerative disorders.  This Special Issue "Bioinorganic Chemistry of Copper" aims to collect original research articles or comprehensive review papers focused on the key role of copper ions in biology.

Dr. Christelle Hureau
Prof. Dr. Ana Maria Da Costa Ferreira
Dr. Gianella Facchin
Guest Editors

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Keywords

  • copper biochemistry
  • copper proteins
  • copper enzymes
  • copper homeostasis
  • copper transport
  • copper bioinspired chemistry
  • copper-targeting drugs
  • copper-related diseases
  • copper-based drugs

Published Papers (15 papers)

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Editorial

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5 pages, 188 KiB  
Editorial
Bioinorganic Chemistry of Copper: From Biochemistry to Pharmacology
by Ana Maria Da Costa Ferreira, Christelle Hureau and Gianella Facchin
Inorganics 2024, 12(4), 97; https://doi.org/10.3390/inorganics12040097 - 28 Mar 2024
Cited by 1 | Viewed by 951
Abstract
Copper is an essential trace element found ubiquitously in humans [...] Full article

Research

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14 pages, 3456 KiB  
Article
Pentadentate and Hexadentate Pyridinophane Ligands Support Reversible Cu(II)/Cu(I) Redox Couples
by Glenn Blade, Andrew J. Wessel, Karna Terpstra and Liviu M. Mirica
Inorganics 2023, 11(11), 446; https://doi.org/10.3390/inorganics11110446 - 20 Nov 2023
Viewed by 1728
Abstract
Two new ligands were synthesized with the goal of copper stabilization, N,N′-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane (PicN4) and N-(methyl),N′-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane (PicMeN4), by selective functionalization of HN4 and TsHN4. These two ligands, when reacted with various copper salts, generated both Cu(II) and Cu(I) [...] Read more.
Two new ligands were synthesized with the goal of copper stabilization, N,N′-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane (PicN4) and N-(methyl),N′-(2-methylpyridine)-2,11-diaza[3,3](2,6)pyridinophane (PicMeN4), by selective functionalization of HN4 and TsHN4. These two ligands, when reacted with various copper salts, generated both Cu(II) and Cu(I) complexes. These ligands and Cu complexes were characterized by various methods, such as NMR, UV-Vis, MS, and EA. Each compound was also examined electrochemically, and each revealed reversible Cu(II)/Cu(I) redox couples. Additionally, stability constants were determined via spectrophotometric titrations, and radiolabeling and cytotoxicity experiments were performed to assess the chelators relevance to their potential use in vivo as 64Cu PET imaging agents. Full article
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13 pages, 3407 KiB  
Article
Exploration of Lycorine and Copper(II)’s Association with the N-Terminal Domain of Amyloid β
by Arian Kola, Ginevra Vigni and Daniela Valensin
Inorganics 2023, 11(11), 443; https://doi.org/10.3390/inorganics11110443 - 18 Nov 2023
Viewed by 1481
Abstract
Lycorine (LYC) is an active alkaloid first isolated from Narcissus pseudonarcissus and found in most Amaryllidaceae plants. It belongs to the same family as galantamine, which is the active component of a drug used for the treatment of Alzheimer’s disease. Similarly to galantamine, [...] Read more.
Lycorine (LYC) is an active alkaloid first isolated from Narcissus pseudonarcissus and found in most Amaryllidaceae plants. It belongs to the same family as galantamine, which is the active component of a drug used for the treatment of Alzheimer’s disease. Similarly to galantamine, LYC is able to suppress induced amyloid β (Aβ) toxicity in differentiated SH-SY5Y cell lines and it can weakly interact with the N-terminal region of Aβ via electrostatic interactions. The N-terminal Aβ domain is also involved in Cu(II)/Cu(I) binding and the formed complexes are known to play a key role in ROS production. In this study, the Aβ–LYC interaction in the absence and in the presence of copper ions was investigated by using the N-terminal Aβ peptide encompassing the first 16 residues. NMR analysis showed that Aβ can simultaneously interact with Cu(II) and LYC. The Cu(II) binding mode remains unchanged in the presence of LYC, while LYC association is favored when an Aβ–Cu(II) complex is formed. Moreover, UV-VIS studies revealed the ability of LYC to interfere with the catalytic activities of the Aβ–Cu(II) complexes by reducing the ascorbate consumption monitored at 265 nm. Full article
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19 pages, 3453 KiB  
Article
Effect of Metal Environment and Immobilization on the Catalytic Activity of a Cu Superoxide Dismutase Mimic
by Micaela Richezzi, Joaquín Ferreyra, Sharon Signorella, Claudia Palopoli, Gustavo Terrestre, Nora Pellegri, Christelle Hureau and Sandra R. Signorella
Inorganics 2023, 11(11), 425; https://doi.org/10.3390/inorganics11110425 - 27 Oct 2023
Cited by 1 | Viewed by 1380
Abstract
The Cu(II)/Cu(I) conversion involves variation in the coordination number and geometry around the metal center. Therefore, the flexibility/rigidity of the ligand plays a critical role in the design of copper superoxide dismutase (SOD) mimics. A 1,3-Bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), a flexible ligand with an N [...] Read more.
The Cu(II)/Cu(I) conversion involves variation in the coordination number and geometry around the metal center. Therefore, the flexibility/rigidity of the ligand plays a critical role in the design of copper superoxide dismutase (SOD) mimics. A 1,3-Bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), a flexible ligand with an N4-donor set, was used to prepare [Cu(pypapn)(ClO4)2], a trans-Cu(II) complex whose structure was determined by the X-ray diffraction. In DMF or water, perchlorate anions are exchanged with solvent molecules, affording [Cu(pypan)(solv)2]2+ that catalyzes O2•− dismutation with a second-order rate constant kMcF = 1.26 × 107 M−1 s−1, at pH 7.8. This high activity results from a combination of ligand flexibility, total charge, and labile binding sites, which places [Cu(pypapn)(solv)2]2+ above other mononuclear Cu(II) complexes with more favorable redox potentials. The covalent anchoring of the alkyne group of the complex to azide functionalized mesoporous silica through “click” chemistry resulted in the retention of the SOD activity and improved stability. A dicationic Cu(II)-N4-Schiff base complex encapsulated in mesoporous silica was also tested as an SOD mimic, displaying higher activity than the free complex, although lower than [Cu(pypapn)(solv)2]2+. The robustness of covalently attached or encapsulated doubly charged Cu(II) complexes in a mesoporous matrix appears as a suitable approach for the design of copper-based hybrid catalysts for O2•− dismutation under physiological conditions. Full article
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16 pages, 3191 KiB  
Article
Antiparasitic Activity of Oxindolimine–Metal Complexes against Chagas Disease
by Marcelo Cecconi Portes, Grazielle Alves Ribeiro, Gustavo Levendoski Sabino, Ricardo Alexandre Alves De Couto, Leda Quércia Vieira, Maria Júlia Manso Alves and Ana Maria Da Costa Ferreira
Inorganics 2023, 11(11), 420; https://doi.org/10.3390/inorganics11110420 - 24 Oct 2023
Viewed by 1454
Abstract
Some copper(II) and zinc(II) complexes with oxindolimine ligands were tested regarding their trypanocidal properties. These complexes have already shown good biological activity in the inhibition of tumor cell proliferation, having DNA and mitochondria as main targets, through an oxidative mechanism, and inducing apoptosis. [...] Read more.
Some copper(II) and zinc(II) complexes with oxindolimine ligands were tested regarding their trypanocidal properties. These complexes have already shown good biological activity in the inhibition of tumor cell proliferation, having DNA and mitochondria as main targets, through an oxidative mechanism, and inducing apoptosis. Herein, we demonstrate that they also have significant activity against the infective trypomastigote forms and the intracellular amastigote forms of T. cruzi, modulated by the metal ion as well as by the oxindolimine ligand. Selective indexes (LC50/IC50) determined for both zinc(II) and copper(II) complexes, are higher after 24 or 48 h incubation with trypomastigotes, in comparison to traditional drugs used in clinics, such as benznidazole, and other metal-based compounds previously reported in the literature. Additionally, tests against amastigotes indicated infection index <10% (% of infected macrophages/average number of amastigotes per macrophage), after 24 or 48 h in the presence of zinc(II) (60–80 µM) or analogous copper(II) complexes (10–25 µM). The copper complexes exhibit further oxidative properties, being able to damage DNA, proteins and carbohydrates, in the presence of hydrogen peroxide, with the generation of hydroxyl radicals. This redox reactivity could explain its better performance towards the parasites in relation to the zinc analogs. However, both copper and zinc complexes display good selective indexes, indicating that the influence of the ligand is also crucial, and is probably related to the inhibition of some crucial proteins. Full article
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12 pages, 2023 KiB  
Article
Synthesis, Characterization, DNA Binding and Cytotoxicity of Copper(II) Phenylcarboxylate Complexes
by Carlos Y. Fernández, Analu Rocha, Mohammad Azam, Natalia Alvarez, Kim Min, Alzir A. Batista, Antonio J. Costa-Filho, Javier Ellena and Gianella Facchin
Inorganics 2023, 11(10), 398; https://doi.org/10.3390/inorganics11100398 - 11 Oct 2023
Viewed by 1389
Abstract
Coordination compounds of copper exhibit cytotoxic activity and are suitable for the search for novel drug candidates for cancer treatment. In this work, we synthesized three copper(II) carboxylate complexes, [Cu2(3-(4-hydroxyphenyl)propanoate)4(H2O)2]·2H2O (C1), [...] Read more.
Coordination compounds of copper exhibit cytotoxic activity and are suitable for the search for novel drug candidates for cancer treatment. In this work, we synthesized three copper(II) carboxylate complexes, [Cu2(3-(4-hydroxyphenyl)propanoate)4(H2O)2]·2H2O (C1), [Cu2(phenylpropanoate)4(H2O)2] (C2) and [Cu2(phenylacetate)4] (C3), and characterized them by elemental analysis and spectroscopic methods. Single-crystal X-ray diffraction of C1 showed the dinuclear paddle-wheel arrangement typical of Cu–carboxylate complexes in the crystal structure. In an aqueous solution, the complexes remain as dimeric units, as studied by UV-visible spectroscopy. The lipophilicity (partition coefficient) and the DNA binding (UV visible and viscosity) studies evidence that the complexes bind the DNA with low Kb constants. In vitro cytotoxicity studies on human cancer cell lines of metastatic breast adenocarcinoma (MDA-MB-231, MCF-7), lung epithelial carcinoma (A549) and cisplatin-resistant ovarian carcinoma (A2780cis), as well as a nontumoral lung cell line (MRC-5), indicate that the complexes are cytotoxic in cisplatin-resistant cells. Full article
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22 pages, 3632 KiB  
Article
Anti-Proliferation and DNA Cleavage Activities of Copper(II) Complexes of N3O Tripodal Polyamine Ligands
by Doti Serre, Sule Erbek, Nathalie Berthet, Christian Philouze, Xavier Ronot, Véronique Martel-Frachet and Fabrice Thomas
Inorganics 2023, 11(10), 396; https://doi.org/10.3390/inorganics11100396 - 9 Oct 2023
Viewed by 1106
Abstract
Four ligands based on the 2-tert-butyl-4-X-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol unit are synthesized: X = CHO (HLCHO), putrescine-pyrene (HLpyr), putrescine (HLamine), and 2-tert-butyl-4-putrescine-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol (H2Lbis). Complexes 1, 2, 3, and 4 are [...] Read more.
Four ligands based on the 2-tert-butyl-4-X-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol unit are synthesized: X = CHO (HLCHO), putrescine-pyrene (HLpyr), putrescine (HLamine), and 2-tert-butyl-4-putrescine-6-{Bis[(6-methoxy-pyridin-2-ylmethyl)-amino]-methyl}-phenol (H2Lbis). Complexes 1, 2, 3, and 4 are formed upon chelation to copper(II). The crystal structure of complex 1 shows a square pyramidal copper center with a very weakly bound methoxypridine moiety in the apical position. The pKa of the phenol moiety is determined spectrophotometrically at 2.82–4.39. All the complexes show a metal-centered reduction in their CV at Epc,red = −0.45 to −0.5 V vs. SCE. The copper complexes are efficient nucleases towards the ϕX174 DNA plasmid in the presence of ascorbate. The corresponding IC50 value reaches 7 μM for 2, with a nuclease activity that follows the trend: 2 > 3 > 1. Strand scission is promoted by the hydroxyl radical. The cytotoxicity is evaluated on bladder cancer cell lines sensitive (RT112) or resistant to cisplatin (RT112 CP). The IC50 of the most active complexes (2 and 4) is 1.2 and 1.0 μM, respectively, for the RT112 CP line, which is much lower than cisplatin (23.8 μM). Full article
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18 pages, 4384 KiB  
Article
Copper(I)/Triphenylphosphine Complexes Containing Naphthoquinone Ligands as Potential Anticancer Agents
by Celisnolia M. Leite, João H. Araujo-Neto, Adriana P. M. Guedes, Analu R. Costa, Felipe C. Demidoff, Chaquip D. Netto, Eduardo E. Castellano, Otaciro R. Nascimento and Alzir A. Batista
Inorganics 2023, 11(9), 367; https://doi.org/10.3390/inorganics11090367 - 9 Sep 2023
Viewed by 1388
Abstract
Four new Cu/PPh3/naphtoquinone complexes were synthesized, characterized (IR, UV/visible, 1D/2D NMR, mass spectrometry, elemental analysis, and X-ray diffraction), and evaluated as anticancer agents. We also investigated the reactive oxygen species (ROS) generation capacity of complex 4, considering the well-established photochemical [...] Read more.
Four new Cu/PPh3/naphtoquinone complexes were synthesized, characterized (IR, UV/visible, 1D/2D NMR, mass spectrometry, elemental analysis, and X-ray diffraction), and evaluated as anticancer agents. We also investigated the reactive oxygen species (ROS) generation capacity of complex 4, considering the well-established photochemical property of naphthoquinones. Therefore, employing the electron paramagnetic resonance (EPR) “spin trap”, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) technique, we identified the formation of the characteristic •OOH species (hydroperoxyl radical) adduct even before irradiating the solution containing complex 4. As the irradiation progressed, this radical species gradually diminished, primarily giving rise to a novel species known as •DMPO-OH (DMPO + •OH radical). These findings strongly suggest that Cu(I)/PPh3/naphthoquinone complexes can generate ROS, even in the absence of irradiation, potentially intensifying their cytotoxic effect on tumor cells. Interpretation of the in vitro cytotoxicity data of the Cu(I) complexes considered their stability in cell culture medium. All of the complexes were cytotoxic to the lung (A549) and breast tumor cell lines (MDA-MB-231 and MCF-7). However, the higher toxicity for the lung (MRC5) and breast (MCF-10A) non-tumoral cells resulted in a low selectivity index. The morphological analysis of MDA-MB-231 cells treated with the complexes showed that they could cause decreased cell density, loss of cell morphology, and loss of cell adhesion, mainly with concentrations higher than the inhibitory concentration of 50% of cell viability (IC50) values. Similarly, the clonogenic survivance of these cells was affected only with concentrations higher than the IC50 values. An antimigratory effect was observed for complexes 1 and 4, showing around 20–40% of inhibition of wound closure in the wound healing experiments. Full article
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15 pages, 3007 KiB  
Article
Symmetrical and Unsymmetrical Dicopper Complexes Based on Bis-Oxazoline Units: Synthesis, Spectroscopic Properties and Reactivity
by James A. Isaac, Gisèle Gellon, Florian Molton, Christian Philouze, Nicolas Le Poul, Catherine Belle and Aurore Thibon-Pourret
Inorganics 2023, 11(8), 332; https://doi.org/10.3390/inorganics11080332 - 11 Aug 2023
Viewed by 1094
Abstract
Copper–oxygen adducts are known for being key active species for the oxidation of C–H bonds in copper enzymes and their synthetic models. In this work, the synthesis and spectroscopic characterizations of such intermediates using dinucleating ligands based on a 1,8 naphthyridine spacer with [...] Read more.
Copper–oxygen adducts are known for being key active species for the oxidation of C–H bonds in copper enzymes and their synthetic models. In this work, the synthesis and spectroscopic characterizations of such intermediates using dinucleating ligands based on a 1,8 naphthyridine spacer with oxazolines or mixed pyridine-oxazoline coordination moieties as binding pockets for copper ions have been explored. On the one hand, the reaction of dicopper(I) complexes with O2 at low temperature led to the formation of a µ-η22 Cu2:O2 peroxido species according to UV-Vis spectroscopy monitoring. The reaction of these species with 2,4-di-tert-butyl-phenolate resulted in the formation of the C–C coupling product, but no insertion of oxygen occurred. On the other hand, the synthesis of dinuclear Cu(II) bis-µ-hydroxido complexes based on pyridine–oxazoline and oxazoline ligands were carried out to further generate CuIICuIII oxygen species. For both complexes, a reversible monoelectronic oxidation was detected via cyclic voltammetry at E1/2 = 1.27 and 1.09 V vs. Fc+/Fc, respectively. Electron paramagnetic resonance spectroscopy (EPR) and UV-Vis spectroelectrochemical methods indicated the formation of a mixed-valent CuIICuIII species. Although no reactivity towards exogeneous substrates (toluene) could be observed, the CuIICuIII complexes were shown to be able to perform hydroxylation on the methyl group of the oxazoline moieties. The present study therefore indicates that the electrochemically generated CuIICuIII species described herein are capable of intramolecular aliphatic oxidation of C–H bonds. Full article
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21 pages, 9382 KiB  
Article
Copper(II) and Platinum(II) Naproxenates: Insights on Synthesis, Characterization and Evaluation of Their Antiproliferative Activities
by Amanda A. Silva, Silmara C. L. Frajácomo, Állefe B. Cruz, Kaio Eduardo Buglio, Daniele Daiane Affonso, Marcelo Cecconi Portes, Ana Lúcia T. G. Ruiz, João Ernesto de Carvalho, Wilton R. Lustri, Douglas H. Pereira, Ana M. da Costa Ferreira and Pedro P. Corbi
Inorganics 2023, 11(8), 331; https://doi.org/10.3390/inorganics11080331 - 10 Aug 2023
Viewed by 1332
Abstract
The growth of antibiotic resistance is a matter of worldwide concern. In parallel, cancer remains one of the main causes of death. In the search for new and improved antiproliferative agents, one of the strategies is the combination of bioactive ligands and metals [...] Read more.
The growth of antibiotic resistance is a matter of worldwide concern. In parallel, cancer remains one of the main causes of death. In the search for new and improved antiproliferative agents, one of the strategies is the combination of bioactive ligands and metals that are already consolidated in the synthesis of metallopharmaceutical agents. Thus, this work deals with the synthesis, characterization, and study of naproxen (Nap)-based complexes of copper(II) and platinum(II) as antiproliferative agents. The copper complex (Cu–Nap) presents a binuclear paddle-wheel structure in a 1 Cu:2 Nap:1 H2O molar composition, in which Cu(II) is bonded to the carboxylate oxygens from naproxenate in a bidentate bridging mode. The platinum complex (Pt–Nap) was identified as the square planar cis-[Pt(Nap)2(DMSO)2] isomer, in which Pt(II) is bonded to the carboxylate oxygen atom of Nap in a monodentate fashion. Both complexes were inactive against the Gram-positive and Gram-negative bacterial strains assessed. Pt–Nap presented low cytostatic behavior over a set of tumor cells, but good viability for normal cells, while Cu–Nap was cytotoxic against all cells, with a cytocidal activity against glioma tumor cells. Full article
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15 pages, 4673 KiB  
Article
Oxidation of Phospholipids by OH Radical Coordinated to Copper Amyloid-β Peptide—A Density Functional Theory Modeling
by Alberto Rovetta, Laura Carosella, Federica Arrigoni, Jacopo Vertemara, Luca De Gioia, Giuseppe Zampella and Luca Bertini
Inorganics 2023, 11(6), 227; https://doi.org/10.3390/inorganics11060227 - 25 May 2023
Viewed by 1214
Abstract
Oxidative stress and metal dyshomeostasis are considered crucial factors in the pathogenesis of Alzheimer’s disease (AD). Indeed, transition metal ions such as Cu(II) can generate reactive oxygen species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the amyloid-beta (Aβ) peptide. [...] Read more.
Oxidative stress and metal dyshomeostasis are considered crucial factors in the pathogenesis of Alzheimer’s disease (AD). Indeed, transition metal ions such as Cu(II) can generate reactive oxygen species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the amyloid-beta (Aβ) peptide. Despite intensive efforts, the mechanisms of ROS-induced molecular damage remain poorly understood. In the present paper, we investigate, on the basis of Density Functional Theory (DFT) computations, a possible mechanism of the OH radical propagation toward membrane phospholipid polar head and fatty acid chains starting from the end-product of the OH radical generation by Cu(II)-Aβ. Using phosphatidylcholine as a model of a single unit inside a membrane, we evaluated the thermochemistry of the OH propagation with the oxidation of a C-H bond and the formation of the radical moiety. The DFT results show that Cu(II)-Aβ-OH can oxidize only sn-2 C-H bonds of the polar head and can easily oxidize the C-H bond adjacent to the carbon–carbon double bond in a mono or bis unsaturated fatty acid chain. These results are discussed on the basis of the recent literature on in vitro Aβ metal-catalyzed oxidation and on the possible implications in the AD oxidative stress mechanism. Full article
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17 pages, 2159 KiB  
Article
Novel Copper(II) Complexes with N4,S-Diallylisothiosemicarbazones as Potential Antibacterial/Anticancer Drugs
by Vasilii Graur, Irina Usataia, Ianina Graur, Olga Garbuz, Paulina Bourosh, Victor Kravtsov, Carolina Lozan-Tirsu, Greta Balan, Valeriu Fala and Aurelian Gulea
Inorganics 2023, 11(5), 195; https://doi.org/10.3390/inorganics11050195 - 30 Apr 2023
Cited by 2 | Viewed by 1505
Abstract
The six new copper(II) coordination compounds [Cu(HL1)Cl2] (1), [Cu(HL1)Br2] (2), [Cu(H2O)(L1)(CH3COO)]·1.75H2O (3), [Cu(HL2)Cl2] (4), [Cu(HL [...] Read more.
The six new copper(II) coordination compounds [Cu(HL1)Cl2] (1), [Cu(HL1)Br2] (2), [Cu(H2O)(L1)(CH3COO)]·1.75H2O (3), [Cu(HL2)Cl2] (4), [Cu(HL2)Br2] (5), [Cu(H2O)(L2)(CH3COO)] (6) were synthesized with 2-formyl- and 2-acetylpyridine N4,S-diallylisothiosemicarbazones (HL1 and HL2). The new isothiosemicarbazones were characterized by NMR, FTIR spectroscopy, and X-ray crystallography ([H2L2]I). All copper(II) coordination compounds were characterized by elemental analysis, FTIR spectroscopy, and molar conductivity of their 1mM methanol solutions. Furthermore, the crystal structure of complex 3 was determined using single-crystal X-ray diffraction analysis. The studied complexes manifest antibacterial and antifungal activities, that in many cases are close to the activity of medical drugs used in this area, and in some cases even exceed them. The complexes 4 and 5 showed the highest indexes of selectivity (280 and 154) and high antiproliferative activity against BxPC-3 cell lines that surpass the activity of Doxorubicin. The complexes 13 also manifest antioxidant activities against cation radicals ABTS•+ that are close to that of trolox, the antioxidant agent used in medicine. Full article
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7 pages, 1295 KiB  
Communication
Evaluation of Membrane Permeability of Copper-Based Drugs
by Evariste Umba-Tsumbu, Ahmed N. Hammouda and Graham Ellis Jackson
Inorganics 2023, 11(5), 179; https://doi.org/10.3390/inorganics11050179 - 23 Apr 2023
Cited by 1 | Viewed by 1367
Abstract
Membrane permeability of copper complexes with potential anti-inflammatory activity were measured using an artificial membrane in a modified Franz cell. Using CuCl2 as the control, all the ligands tested enhanced the diffusion of copper, with enhancement factors ranging from 2 to 7. [...] Read more.
Membrane permeability of copper complexes with potential anti-inflammatory activity were measured using an artificial membrane in a modified Franz cell. Using CuCl2 as the control, all the ligands tested enhanced the diffusion of copper, with enhancement factors ranging from 2 to 7. Octanol/water partition coefficients (log Ko/w) were measured and correlated with the permeability coefficients (Kp). In addition, chemical speciation was used to determine the predominant complex in solution at physiological pH. No correlation was found between the measured permeability coefficients and either molecular weight (MW) or log Ko/w. Full article
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Review

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23 pages, 3440 KiB  
Review
The Importance of Being Casiopeina as Polypharmacologycal Profile (Mixed Chelate–Copper (II) Complexes and Their In Vitro and In Vivo Activities)
by Zenayda Aguilar-Jiménez, Adrián Espinoza-Guillén, Karen Resendiz-Acevedo, Inés Fuentes-Noriega, Carmen Mejía and Lena Ruiz-Azuara
Inorganics 2023, 11(10), 394; https://doi.org/10.3390/inorganics11100394 - 7 Oct 2023
Cited by 7 | Viewed by 2283
Abstract
In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas®, as the first copper (II) compounds proposed as anticancer drugs in 1988 and 1992. In the late twentieth century, [...] Read more.
In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas®, as the first copper (II) compounds proposed as anticancer drugs in 1988 and 1992. In the late twentieth century, the use of essential metals as anticancer agents was not even considered, except for their antifungal or antibacterial effects; also, copper, as gold salts, was used for arthritis problems. The use of essential metals as anticancer drugs to diminish the secondary toxic effects of Cisplatin was our driving force: to find less toxic and even more economical compounds under the rational design of metal chelate complexes. Due to their chemical properties, copper compounds were the choice to continue anticancer drug development. In this order of ideas, the rational designs of mixed chelate–copper (II) complexes (Casiopeínas, (Cas) homoleptic or heteroleptic, depending on the nature of the secondary ligand) were synthesized and fully characterized. In the search for new, more effective, and less toxic drugs, Casiopeína® (Cas) emerged as a family of approximately 100 compounds synthesized from coordinated Cu(II) complexes with proven antineoplastic potential through cytotoxic action. The Cas have the general formula [Cu(N–N)(N–O)]NO3 and [Cu(N–N)(O–O)]NO3, where N–N is an aromatic substituted diimine (1,10-phenanthroline or 2,2′-bipyridine), and the oxygen donor (O–O) is acetylacetonate or salicylaldehyde. Lately, some similar compounds have been developed by other research groups considering a similar hypothesis after Casiopeína’s discoveries had been published, as described herein. As an example of translational medicine criteria, we have covered each step of the established normative process for drug development, and consequently, one of the molecules (Casiopeína III ia (CasIIIia)) has reached the clinical phase I. For these copper compounds, other activities, such as antibacterial, antiparasitic and antiviral, have been discovered. Full article
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13 pages, 2009 KiB  
Review
Probing the Bioinorganic Chemistry of Cu(I) with 111Ag Perturbed Angular Correlation (PAC) Spectroscopy
by Victoria Karner, Attila Jancso and Lars Hemmingsen
Inorganics 2023, 11(10), 375; https://doi.org/10.3390/inorganics11100375 - 23 Sep 2023
Viewed by 998
Abstract
The two most common oxidation states of copper in biochemistry are Cu(II) and Cu(I), and while Cu(II) lends itself to spectroscopic interrogation, Cu(I) is silent in most techniques. Ag(I) and Cu(I) are both closed-shell d10 monovalent ions, and to some extent share [...] Read more.
The two most common oxidation states of copper in biochemistry are Cu(II) and Cu(I), and while Cu(II) lends itself to spectroscopic interrogation, Cu(I) is silent in most techniques. Ag(I) and Cu(I) are both closed-shell d10 monovalent ions, and to some extent share ligand and coordination geometry preferences. Therefore, Ag(I) may be applied to explore Cu(I) binding sites in biomolecules. Here, we review applications of 111Ag perturbed angular correlation (PAC) of γ-ray spectroscopy aimed to elucidate the chemistry of Cu(I) in biological systems. Examples span from small blue copper proteins such as plastocyanin and azurin (electron transport) over hemocyanin (oxygen transport) to CueR and BxmR (metal-ion-sensing proteins). Finally, possible future applications are discussed. 111Ag is a radionuclide which undergoes β-decay to 111Cd, and it is a γ-γ cascade of the 111Cd daughter nucleus, which is used in PAC measurements. 111Ag PAC spectroscopy may provide information on the coordination environment of Ag(I) and on the structural relaxation occurring upon the essentially instantaneous change from Ag(I) to Cd(II). Full article
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