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Inorganics
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Noble Metals in Medicinal Inorganic Chemistry
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Noble Metals in Medicinal Inorganic Chemistry

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 6675

Special Issue Editors

Dr. Esteban Rodríguez-Arce

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Guest Editor
Departamento de Química Inorgánica y Analítica, Universidad de Chile, Casilla 233, Santiago, Chile
Interests: bioinorganic chemistry; inorganic medicinal chemistry; coordination compounds; organometallic compounds; cancer; Chagas disease; human African trypanosomiasis
Prof. Dr. Dinorah Gambino

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Guest Editor
Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay
Interests: vanadium chemistry and biological inorganic chemistry; bioorganometallic chemistry; medicinal inorganic chemistry; metal-based drugs; drug discovery for neglected diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The study and development of noble metal-based drugs is a promising approach to designing new drugs for treating several diseases. Cisplatin and other platinum-based compounds are powerful chemotherapeutic agents used currently in the clinical treatment of cancer. The chemical and biological properties of coordination and organometallic compounds have allowed the design of new metallodrugs that include different metal ions. Ruthenium-based compounds have seen advanced clinical trials as potential novel anticancer drugs. Gold-based drugs are currently used in the clinic for the treatment of rheumatoid arthritis. These metal ions and rhodium, iridium, palladium, osmium, and other denominated noble elements have been the subject of study of several investigations due to their interesting pharmacological properties; therefore, it is relevant to the development of novel metal compounds with highlighted pharmacological properties, such as anticancer, antirheumatic, antimalarial, antibacterial, antiparasitic, antifungal, and antiviral drugs.

In this Special Issue, we wish to cover the most recent advances in the development of noble metals in medicinal inorganic chemistry by hosting a mix of original research articles and reviews.

Dr. Esteban Rodríguez-Arce
Prof. Dr. Dinorah Gambino
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Inorganics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metallodrugs
  • bioactive noble metals
  • medicinal inorganic chemistry
  • coordination and organometallic compounds
  • biological studies
  • mechanism of action
  • pharmacological properties

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Published Papers (5 papers)

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Research

22 pages, 7851 KiB  
Article
1,10-Phenanthroline and 4,5-Diazafluorene Ketones and Their Silver(I) and Platinum(II) Complexes: Syntheses and Biological Evaluation as Antiproliferative Agents
by Leonardo Sandin-Mazzondo, Jesús M. Martínez-Ilarduya, Jesús A. Miguel, Camino Bartolomé and Concepción Alonso
Inorganics 2025, 13(1), 6; https://doi.org/10.3390/inorganics13010006 - 28 Dec 2024
Viewed by 531
Abstract
Using non-classical polyfluorophenyl ligands in Pt(II) complexes and other transition metals such as silver is a promising approach in the search for more effective and safer antitumoral drugs. In this work, a series of chelating N-donor ligands with 1,10-phenanthroline and 4,5-diazafluorene backbones [...] Read more.
Using non-classical polyfluorophenyl ligands in Pt(II) complexes and other transition metals such as silver is a promising approach in the search for more effective and safer antitumoral drugs. In this work, a series of chelating N-donor ligands with 1,10-phenanthroline and 4,5-diazafluorene backbones and ketone groups were synthesized (1,10-phenanthroline-5,6-dione, 1; (R/S)-6-hydroxy-6-(2-oxypropyl)-1,10-phenanthroline-5(6H)-one, 2; 4,5-diazafluoren-9-one, 3; 9-hydroxy-9-(2-oxypropyl)-4,5-diazafluorene, 4). The corresponding [Ag(N,N)2]NO3 (1Ag–4Ag) and [Pt(C6F5)2(N,N)] (1Pt–4Pt) complexes were prepared. The stability of these complexes in DMSO solution was studied, showing no dissociation over 48 h for almost all complexes, except 3Pt. The compounds were characterized by NMR (1H, 13C, and 19F), MS, and X-ray diffraction (2, 4, 1Ag, 3Ag, 1Pt, and 3Pt). A study of the cytotoxicity of the compounds in lung carcinoma (A-549) and fetal lung fibroblast (MRC-5) cell lines was performed. Compounds 1, 2, 1Ag, 2Ag, 3Ag, 1Pt, 3Pt, and 4Pt were more active against A-549 cells than cisplatin. Complexes 3Ag and 1Pt showed an acceptable SI and better selectivity than cisplatin, proving that silver(I) complexes and Pt(polyfluorophenyl) complexes are valuable options in searching for new antitumoral drugs. Full article
(This article belongs to the Special Issue Noble Metals in Medicinal Inorganic Chemistry)
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12 pages, 1575 KiB  
Article
Arene Ruthenium Complexes Specifically Inducing Apoptosis in Breast Cancer Cells
by Adriana Grozav, Thomas Cheminel, Ancuta Jurj, Oana Zanoaga, Lajos Raduly, Cornelia Braicu, Ioana Berindan-Neagoe, Ovidiu Crisan, Luiza Gaina and Bruno Therrien
Inorganics 2024, 12(11), 287; https://doi.org/10.3390/inorganics12110287 - 2 Nov 2024
Viewed by 1062
Abstract
Monocationic arene ruthenium complexes (RuL1–RuL4) incorporating phenothiazinyl-hydrazinyl-thiazole ligands (L1–L4) have been synthesized, characterized and evaluated as anticancer agents. Their cytotoxicity, antiproliferative activity and alteration of apoptotic gene expression were studied on [...] Read more.
Monocationic arene ruthenium complexes (RuL1–RuL4) incorporating phenothiazinyl-hydrazinyl-thiazole ligands (L1–L4) have been synthesized, characterized and evaluated as anticancer agents. Their cytotoxicity, antiproliferative activity and alteration of apoptotic gene expression were studied on three cancer cell lines, a double positive breast cancer cell line MCF-7 and two triple negative breast cancer cell lines Hs578T and MDA-MB-231. All arene ruthenium complexes were able to reduce the viability of the breast cancer cell lines, with the highest cytotoxicities being recorded for the [(p-cymene)RuL3Cl]+ (RuL3) complex on the MCF-7 (IC50 = 0.019 µM) and Hs578T cell lines (IC50 = 0.095 µM). In the double positive MCF-7 breast cancer cells, the complexes [(p-cymene)RuL1Cl]+ (RuL1) and [(p-cymene)RuL2Cl]+ (RuL2) significantly upregulated pro-apoptotic genes including BAK, FAS, NAIP, CASP8, TNF, XIAP and BAD, while downregulating TNFSF10. In the triple negative breast cancer cell line Hs578T, RuL1 reduced TNFSF-10 and significantly upregulated BAK, CASP8, XIAP, FADD and BAD, while complex RuL2 also increased BAK and CASP8 expression, but had limited effects on other genes. The triple negative MDA-MB-231 cancer cells treated with RuL1 upregulated NOD1 and downregulated p53, while RuL2 significantly downregulated p53, XIAP and TNFSF10, with minor changes in other genes. The significant alterations in the expression of key apoptotic genes suggest that such complexes have the potential to target cancer cells. Full article
(This article belongs to the Special Issue Noble Metals in Medicinal Inorganic Chemistry)
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11 pages, 1400 KiB  
Article
Crystal Structure and Anti-Proliferative and Mutagenic Evaluation of the Palladium(II) Complex of Deoxyalliin
by Tuany Zambroti Candido, Mariana Mazzo Quintanilha, Bianca Alves Schimitd, Déborah de Alencar Simoni, Douglas Hideki Nakahata, Raphael Enoque Ferraz de Paiva, Igor Henrique Cerqueira, Flávia Aparecida Resende, João Ernesto Carvalho, Ana Lucia Tasca Gois Ruiz, Carmen Silvia Passos Lima and Pedro Paulo Corbi
Inorganics 2024, 12(7), 194; https://doi.org/10.3390/inorganics12070194 - 18 Jul 2024
Cited by 1 | Viewed by 1340
Abstract
Platinum(II) and palladium(II) complexes have been investigated as potential anticancer drugs since the serendipitous discovery of the antineoplastic activities of cisplatin in the 1960s. Skin cancer is considered the most common malignant neoplasm that affects humans, and melanoma is the most lethal type [...] Read more.
Platinum(II) and palladium(II) complexes have been investigated as potential anticancer drugs since the serendipitous discovery of the antineoplastic activities of cisplatin in the 1960s. Skin cancer is considered the most common malignant neoplasm that affects humans, and melanoma is the most lethal type of skin cancer. Surgical excision is the main form of treatment, which also may include radiotherapy, systemic chemotherapy, and immunotherapy. In this work, new insights concerning the structural characterization and in vitro anti-proliferative activity of the palladium(II) complex with the amino acid deoxyalliin (Pd-sac) against a panel of thirteen human tumor cells, with emphasis on skin cancer cell lines, are presented. The composition of the complex was confirmed by elemental analysis as [Pd(C6H10NO2S)2]. The structure of the complex was elucidated for the first time by a single-crystal X-ray diffraction technique. Each deoxyalliin molecule coordinates in a bidentate N,S-mode to palladium(II) in a trans-configuration analogous to the platinum(II) deoxyalliin complex early reported. As the main result, the Pd-sac complex showed a selective anti-proliferative activity against melanoma (UACC-62, TGI = 63.5 µM), while both deoxyalliin and K2PdCl4 were inactive against all cell lines. Moreover, Pd-sac did not affect the proliferation of non-tumorigenic keratinocytes (HaCaT, TGI > 586 µM) and was non-mutagenic in the Ames assay. The results open new perspectives for in vivo studies concerning the application of the Pd-sac complex in the treatment of melanoma. Full article
(This article belongs to the Special Issue Noble Metals in Medicinal Inorganic Chemistry)
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23 pages, 8826 KiB  
Article
Synthesis, Characterization, DNA, Fluorescence, Molecular Docking, and Antimicrobial Evaluation of Novel Pd(II) Complex Containing O, S Donor Schiff Base Ligand and Azole Derivative
by Maged S. Al-Fakeh, Muneera Alrasheedi, Ard Elshifa M. E. Mohammed, Ahmed B. M. Ibrahim, Sadeq M. Al-Hazmy, Ibrahim A. Alhagri and Sabri Messaoudi
Inorganics 2024, 12(7), 189; https://doi.org/10.3390/inorganics12070189 - 11 Jul 2024
Cited by 1 | Viewed by 1278
Abstract
Pd(II) with the Schiff base ligand 2-Hydroxy-3-Methoxy Benzaldehyde-Thiosemicarbazone (HMBATSC) (L2) and 2-aminobenzothiazole (2-ABZ) (L1) was synthesized. The Schiff base ligand and the Palladium(II) complex were characterized by C.H.N.S, FT-IR, conductance studies, magnetic susceptibility, XRD, and TGA. From the elemental analysis and spectral data, [...] Read more.
Pd(II) with the Schiff base ligand 2-Hydroxy-3-Methoxy Benzaldehyde-Thiosemicarbazone (HMBATSC) (L2) and 2-aminobenzothiazole (2-ABZ) (L1) was synthesized. The Schiff base ligand and the Palladium(II) complex were characterized by C.H.N.S, FT-IR, conductance studies, magnetic susceptibility, XRD, and TGA. From the elemental analysis and spectral data, the complex was proposed to have the formula [Pd(HMBATSC)(2-ABZ)H2O]. The interaction between the Pd(II) complex and DNA was examined through various methods, including UV–Vis spectroscopy, fluorescence techniques, and DNA viscosity titrations. The findings provided strong evidence that the interaction between the Pd(II) complex and DNA occurs through the intercalation mode. The analysis yielded the following values: a Stern–Volmer quenching constant (ksv) of 1.67 × 104 M−1, a quenching rate constant (kq) of 8.35 × 1011 M−1 s−1, a binding constant (kb) of 5.20 × 105 M−1, and a number of binding the sites (n) of 1.392. DFT studies suggest that the azole derivative may act as an electron donor through pyridine nitrogen, while the Schiff base ligand may act as an electron donor via oxygen and sulfur atoms. TDDFT calculations indicate that the intramolecular charge transfer from the Schiff base to Pd(II) is responsible for the complex’s fluorescence quenching. The powder X-ray diffraction data revealed that the complex is arranged in a monoclinic system. The resulting Pd(II) complex was investigated for its antimicrobial activity and demonstrated antibacterial efficiency. Interestingly, it showed potent activity against E. coli and E. niger that was found to be more powerful than that recorded for Neomycin. Full article
(This article belongs to the Special Issue Noble Metals in Medicinal Inorganic Chemistry)
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17 pages, 3146 KiB  
Article
Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach
by Javiera Órdenes-Rojas, Paola Risco, José Ortega-Campos, Germán Barriga-González, Ana Liempi, Ulrike Kemmerling, Dinorah Gambino, Lucía Otero, Claudio Olea Azar and Esteban Rodríguez-Arce
Inorganics 2024, 12(5), 133; https://doi.org/10.3390/inorganics12050133 - 3 May 2024
Viewed by 1607
Abstract
In the search for a more effective chemotherapy for the treatment of Chagas’ disease, caused by Trypanosoma cruzi parasite, the use of gold compounds may be a promising approach. In this work, four gold(I) compounds [AuCl(HL)], (HL = bioactive 5-nitrofuryl containing thiosemicarbazones) were [...] Read more.
In the search for a more effective chemotherapy for the treatment of Chagas’ disease, caused by Trypanosoma cruzi parasite, the use of gold compounds may be a promising approach. In this work, four gold(I) compounds [AuCl(HL)], (HL = bioactive 5-nitrofuryl containing thiosemicarbazones) were studied. The compounds were theoretically characterized, showing identical chemical structures with the metal ion located in a linear coordination environment and the thiosemicarbazones acting as monodentate ligands. Cyclic voltammetry and Electron Spin Resonance (ESR) studies demonstrated that the complexes could generate the nitro anion radical (NO2−) by reduction of the nitro moiety. The compounds were evaluated in vitro on the trypomastigote form of T. cruzi and human cells of endothelial morphology. The gold compounds studied showed activity in the micromolar range against T. cruzi. The most active compounds (IC50 of around 10 μM) showed an enhancement of the antiparasitic activity compared with their respective bioactive ligands and moderate selectivity. To get insight into the anti-chagasic mechanism of action, the intracellular free radical production capacity of the gold compounds was assessed by ESR and fluorescence measurements. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and redox cycling processes were characterized. The potential oxidative stress mechanism against T. cruzi was confirmed. Full article
(This article belongs to the Special Issue Noble Metals in Medicinal Inorganic Chemistry)
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