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In this study, we demonstrate that ferroptosis is a component of the cell death mechanism induced by auranofin in HT-1080 cells, in contrast to the gold(III) compounds [Au(phen)Cl 2 ]PF 6 and [Au(bnpy)Cl 2 ]. Additionally, we identify a potential role of Prdx6 in modulating the sensitivity of A-375 cells to auranofin treatment, whereas the gold(III) compounds evaluated here exhibit Prdx6-independent cytotoxicity. Finally, using mass spectrometry, we show that auranofin binds selectively to the catalytic Cys47 residue of Prdx6 in vitro under acidic conditions. No binding was observed with the C47S mutant or at neutral pH., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl 2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI 50 of 10.5 μM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 μM., (© 2023 Wiley-VCH GmbH.)

A low pKa (5.2), high polarizable volume (3.8 Å), and proneness to oxidation under ambient conditions make selenocysteine (Sec, U) a unique, natural reactive handle present in most organisms across all domains of life. Sec modification still has untapped potential for site-selective protein modification and probing. Herein we demonstrate the use of a cyclometalated gold(III) compound, [Au(bnpy)Cl 2 ], in the arylation of diselenides of biological significance, with a scope covering small molecule models, peptides, and proteins using a combination of multinuclear NMR (including 77 Se NMR), and LC-MS. Diphenyl diselenide (Ph-Se) 2 and selenocystine, (Sec) 2 , were used for reaction optimization. This approach allowed us to demonstrate that an excess of diselenide (Au/Se-Se) and an increasing water percentage in the reaction media enhance both the conversion and kinetics of the C-Se coupling reaction, a combination that makes the reaction biocompatible. The C-Se coupling reaction was also shown to happen for the diselenide analogue of the cyclic peptide vasopressin ((Se-Se)-AVP), and the Bos taurus glutathione peroxidase (GPx1) enzyme in ammonium acetate (2 mM, pH=7.0). The reaction mechanism, studied by DFT revealed a redox-based mechanism where the C-Se coupling is enabled by the reductive elimination of the cyclometalated Au(III) species into Au(I)., (© 2024 Wiley-VCH GmbH.)

This article describes the in vitro antibacterial and β-lactamase inhibition of a novel silver(I) complex with the sulfonamide probenecid (Ag-PROB). The formula Ag 2 C 26 H 36 N2O 8 S 2 ·2H 2 O for the Ag-PROB complex was proposed based on elemental analysis. High-resolution mass spectrometric studies revealed the existence of the complex in its dimeric form. Infrared, nuclear magnetic resonance spectroscopies and Density Functional Theory calculations indicated a bidentate coordination of probenecid to the silver ions by the oxygen atoms of the carboxylate. In vitro antibacterial activities of Ag-PROB showed significant growth inhibitory activity over Mycobacterium tuberculosis, S. aureus, and P. aeruginosa PA01biofilm-producers, B. cereus, and E. coli. The Ag-PROB complex was active over multi-drug resistant of uropathogenic E. coli extended spectrum β-lactamases (ESBL) producing (EC958 and BR43), enterohemorrhagic E. coli (O157:H7) and enteroaggregative E. coli (O104:H4). Ag-PROB was able to inhibit CTX-M-15 and TEM-1B ESBL classes, at concentrations below the minimum inhibitory concentration for Ag-PROB, in the presence of ampicillin (AMP) concentration in which EC958 and BR43 bacteria were resistant in the absence of Ag-PROB. These results indicate that, in addition to ESBL inhibition, there is a synergistic antibacterial effect between AMP and the Ag-PROB. Molecular docking results revealed potential key residues involved in interactions between Ag-PROB, CTX-M-15 and TEM1B, suggesting the molecular mechanism of the ESBL inhibition. The obtained results added to the absence of mutagenic activity and low cytotoxic activity over non-tumor cell of the Ag-PROB complex open a new perspective for future in vivo tests demonstrating its potential of use as an antibacterial agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The aims of this work were to evaluate the antibacterial and antiproliferative potential in vitro of the metal complex with 4-aminobenzoic acid (Ag-pABA) and a drug delivery system based on bacterial cellulose (BC-Ag-pABA). The Ag-pABA complex was characterized by elemental analysis, high resolution mass spectrometry and single-crystal X-ray diffraction techniques, which indicated a 1:2 metal/pABA composition plus a nitrate ion coordinated to silver by the oxygen atom, with the coordination formula [Ag (C 7 H 7 NO 2 ) 2 (NO 3 )]. The coordination of pABA to the silver ion occurred by the nitrogen atom. The in vitro antibacterial activity of the complex evaluated by minimum inhibitory concentration assays demonstrated the effective growth inhibitory activity against Gram-positive, Gram-negative biofilm producers and acid-alcohol resistant Bacillus. The antiproliferative activities against a panel of eight tumor cells demonstrated the activity of the complex with a significant selectivity index (SI). The DNA interaction capacity and the Ames Test indicated the absence of mutagenicity. The BC-Ag-pABA composite showed an effective capacity of sustained release of Ag-pABA. The observed results validate further studies on its mechanisms of action and the conditions that mediate the in vivo biological effects using animal models to confirm its safety and effectiveness for treatment of skin and soft tissues infected by bacterial pathogens, urinary tract infections and cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cisplatin is widely used to treat different types of cancer, but its severe side effects are the major disadvantage of this treatment. Therefore, other metals are currently the subject of research in the rational development of anticancer drugs, such as copper, that has been demonstrated to be promising in this scenario. Here, we evaluated the effects of two novel copper complexes against breast cancer cell lines, and also examined the influence of overexpressing copper transporter 1 (CTR1) on the cytotoxicity of these complexes. Complex (1) [Cu(sdmx - ) 2 (phen)] showed low IC 50 values, induced intense cell morphological changes and arrested the cell cycle at the sub-G1 phase in cancer cells. Complex (1) was tested in transfected cells overexpressing the CTR1 receptor in order to compare its steric effects with a less bulky ligand and more labile complex (2) [CuCl 2 (impy)]. A significant reduction of IC 50 value was observed in CTR1 overexpressing cells for complex (2) (32 μM to 20 μM) as compared to (1) (2.78 μM to 3.41 μM), evidencing a possible uptake through copper reduction (Cu +2  → Cu +1 ) mediated by CTR1. Thus, considering that CTR1 is a mediator of metallodrugs uptake, the development of strategies that use rational drug design is important in order to improve the therapeutic efficacy through greater specificity and consecutive reduction of side effects. Here we show the example for the case of copper(II) complexes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen) 2 ] + , was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen) 2 ] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2'-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr - ) 2 (phen)] (1) and [Cu(sdmx - ) 2 (phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N) 2 ] + , [Cu(I)(sulfa)(N^N)] + and [Cu(I)(sulfa) 2 ] + species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Reaction of the Au-C N chelate [Au(bnpy)Cl 2 ] with the full-length zinc finger (ZnF; ZnCys 3 His) of HIV nucleocapsid protein NCp7 results in C-S aryl transfer from the Au III organometallic species to a cysteine of the ZnF. The reaction is general and occurs even for finger 3 of the transcription factor Sp1, containing a ZnCys 2 His 2 coordination sphere. This reaction is the first demonstration of group transfer from a coordination compound to biologically important zinc fingers, and is especially noteworthy for the ZnCys 2 His 2 transcription factors. The work expands the corpus of organometallic species which can efficiently modify biomolecules through C-atom transfer. The electronic features of the gold compound leading to this unexpected reaction were explored by X-ray absorption spectroscopy., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

It is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N , N ', N ''-donating imine ligand led to a mononuclear compound, namely di-chlorido-[ N , N -dimethyl- N '-(pyridin-2-yl-methyl-idene)ethane-1,2-di-amine]copper(II) monohydrate, [CuCl 2 (C 10 H 15 N 3 )]·H 2 O, 1 , while the N , N ', O -donating imine ligand produced a binuclear metal complex, namely μ 2 -chlorido-di-chlorido-(μ 2 -2-{[2-(di-methyl-amino)-ethyl]imino-methyl}phenolato)( N , N -dimethyl-ethylene-di-amine)-dicopper(II) 0.11-hydrate, [Cu 2 (C 11 H 15 N 2 O)Cl 3 (C 4 H 12 N 2 )]·0.11H 2 O, 2 . The structure of 2 is a remarkable example of a binuclear copper(II) complex containing a single substituted 2-imino-methyl-phenolate ligand that has two copper(II) sites in square-pyramidal coordination.

A gold(III) salt of composition [AuCl 2 (C 12 H 8 N 2 )]PF 6 was prepared and characterized by elemental and mass spectrometric analysis (ESI(+)-QTOF-MS), 1 H nuclear magnetic resonance measurements and by single-crystal X-ray diffraction. The square-planar coordination sphere of Au III comprises the bidentate 1,10-phenanthroline ligand and two chloride ions, with the Au III ion only slightly shifted from the least-squares plane of the ligating atoms (r.m.s. = 0.018 Å). In contrast to two other previously reported Au III -phenantroline structures that are stabilized by inter-actions involving the chlorido ligands, the packing of the title compound does not present these features. Instead, the hexa-fluorido-phosphate counter-ion gives rise to anion⋯π inter-actions that are a crucial factor for the crystal packing.