Platinum Group Metals and Their Complexes: Synthesis, Characteristics and Potential Medical Applications

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 8579

Special Issue Editor

Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, 6020 Innsbruck, Austria
Interests: bioinorganic and medicinal chemistry; metal-based drugs development; anticancer drugs research; bioanalytical chemistry

Special Issue Information

Dear Colleagues,

The platinum-based drugs cisplatin, carboplatin, and oxaliplatin are extensively used in cancer chemotherapy. Nevertheless, their clinical effectiveness is often affected by severe side effects and acquired and/or intrinsic tumor resistance. A plethora of Pt(II) and Pt(IV) complexes have been synthesized and investigated during the past several decades in an attempt to overcome these limitations and obtain a superior platinum-based chemotherapeutic. The development of multifunctional Pt(IV) prodrugs is one example of a promising approach to overcome resistance in some malignancy types. Complexes of other platinum group metals have also shown substantial potential as candidates for novel anticancer drugs. Prominent examples comprise the ruthenium compounds NAMI-A, KP1339, and RAPTA-C. Platinum group metal complexes have also been investigated as antimicrobial agents and some promising results have been demonstrated, including activity against antibiotic-resistant bacteria.

This Special Issue aims to capture the current advances in the field of metallodrug development with a focus on platinum group metal (Ru, Rh, Pd, Os, Ir, and Pt) complexes with antineoplastic and/or antibacterial activity. 

Dr. Hristo P. Varbanov
Guest Editor

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Keywords

  • platinum-based chemotherapeutics
  • metallodrug development
  • platinum complexes
  • ruthenium complexes
  • rhodium complexes
  • palladium complexes

Published Papers (6 papers)

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Research

26 pages, 722 KiB  
Article
Cytotoxic Impact of Fluorinated Ligands in Equatorial Position of Trans-Configured Diam(m)inetetracarboxylatoplatinum(IV) Complexes
by Yvonne Lerchbammer-Kreith, Michaela Hejl, Dominik Wenisch, Michael A. Jakupec, Mathea S. Galanski and Bernhard K. Keppler
Inorganics 2023, 11(10), 411; https://doi.org/10.3390/inorganics11100411 - 17 Oct 2023
Viewed by 1248
Abstract
A series of thirty novel tetracarboxylatoplatinum(IV) complexes in trans-configuration featuring combinations of mixed ammine, methylamine, dimethylamine, and cyclopentylamine ligands as well as acetato/propanoato and trifluoropropanoato ligands was synthesised. The platinum(IV) complexes were characterised by one- and two-dimensional multinuclear NMR spectroscopy (1 [...] Read more.
A series of thirty novel tetracarboxylatoplatinum(IV) complexes in trans-configuration featuring combinations of mixed ammine, methylamine, dimethylamine, and cyclopentylamine ligands as well as acetato/propanoato and trifluoropropanoato ligands was synthesised. The platinum(IV) complexes were characterised by one- and two-dimensional multinuclear NMR spectroscopy (1H, 13C, 15N, 19F, 195Pt), ESI-MS, elemental analysis, and X-ray diffraction. Additional parameters such as reduction behaviour and lipophilicity were measured via NMR spectroscopy and RP-HPLC, revealing slow reduction and a broad spectrum of log kw values in line with the respective ligand combination. In order to determine structure–activity relationships, cytotoxic activity was evaluated via the MTT assay in three human cancer cell lines (CH1/PA-1, ovarian teratocarcinoma, SW480, colon adenocarcinoma, A549, non-small-cell lung carcinoma). The induction of apoptosis and necrosis was determined in SW480 cells via the flow-cytometric annexin V/PI assay. In general, a tendency of higher lipophilicity leading to higher cytotoxicity was noticed. In contrast, lipophilicity alone plays a subordinate role for the induction of apoptosis, which strongly depends on the combination of am(m)ine and trifluoropropanoato ligands. Full article
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20 pages, 6161 KiB  
Article
Benzimidazole-Based NHC Metal Complexes as Anticancer Drug Candidates: Gold(I) vs. Platinum(II)
by Paul Kapitza, Patricia Grabher, Amelie Scherfler, Klaus Wurst, Brigitte Kircher, Ronald Gust and Hristo P. Varbanov
Inorganics 2023, 11(7), 293; https://doi.org/10.3390/inorganics11070293 - 11 Jul 2023
Cited by 2 | Viewed by 1600
Abstract
Herein, we present a comparative study on the chemistry and biological activity of N-heterocyclic carbene (NHC)Pt(II)/Au(I) complexes. Accordingly, representative compounds of the cis/trans- [PtL2X2] (X = Cl (5, 6) or I (7 [...] Read more.
Herein, we present a comparative study on the chemistry and biological activity of N-heterocyclic carbene (NHC)Pt(II)/Au(I) complexes. Accordingly, representative compounds of the cis/trans- [PtL2X2] (X = Cl (5, 6) or I (7, 8)), [PtL3Cl]+ (9), [AuLX] (X = Cl (10) or I (11)), and [AuL2]+ (12) type, where L is 1,3-diethylbenzimidazol-2-ylidene, were synthesized and characterized in detail to elucidate the role of the metal center on their physicochemical and biological properties. The stability of the complexes in the presence of cell culture medium and their reactivity toward relevant biomolecules were investigated by RP-HPLC. In addition, their effects on plasmid DNA and in vitro cytotoxicity in ovarian cancer cells and non-malignant fibroblasts were evaluated. Cationic [AuL2]+ and [PtL3X]+ species displayed the highest cytotoxicity and stability in cell culture medium in the series. They exhibited IC50 values lower than the established metallodrugs cisplatin and auranofin in both wild-type and cisplatin-resistant ovarian cancer cells, being able to circumvent cisplatin resistance. Finally, Pt(II)–NHC complexes form 5′-guanosine monophosphate adducts under physiologically relevant conditions and interact with plasmid DNA in contrast to their Au(I) analogs, corroborating their distinct modes of action. Full article
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14 pages, 3233 KiB  
Article
Synthesis, Crystal Structure, Hirshfeld Surfaces Analysis, Interaction with DNA and Comparation of Different Bases in Hirshfeld Atom Refinement of New Polymorph of Chlorido(η6-p-cymene)(diclofenac)Ruthenium(II) Organometallic Compound
by Martin Schoeller, Milan Piroš, Karol Lušpai, Jana Braniša and Ján Moncol
Inorganics 2023, 11(5), 190; https://doi.org/10.3390/inorganics11050190 - 27 Apr 2023
Viewed by 1418
Abstract
A new polymorph of the ruthenium(II) diclofenac complex with formula [Ru(p-cymene)(diclo)Cl] was synthesized, and its crystal structure was solved by single crystal X-ray diffraction. The structure was refined by HAR, using five different relativistic bases sets (x2c-SVP, jorge-DZP-DKH, jorge-TZP-DKH, x2c-TZVP, and x2c-TZVPP) and [...] Read more.
A new polymorph of the ruthenium(II) diclofenac complex with formula [Ru(p-cymene)(diclo)Cl] was synthesized, and its crystal structure was solved by single crystal X-ray diffraction. The structure was refined by HAR, using five different relativistic bases sets (x2c-SVP, jorge-DZP-DKH, jorge-TZP-DKH, x2c-TZVP, and x2c-TZVPP) and three effective core potential basis sets (ECP-def2-SVP, ECP-def2-TZVP, and ECP-def2-TZVPP). Their influence on the structure parameters was compared. The analysis of the supramolecular structure of the HAR/non-HAR structures, as well as of the orthorhombic polymorph, was supported by the calculation and analysis of the Hirshfeld surfaces. The best results were observed for HAR using triple-zeta-based sets. No significant effect of base choice on Hirshfeld surfaces was observed. A study of the ability of the complex to interact with ct-DNA was also performed. The complex was shown to interact with ct-DNA, but the mode of interaction is not fully elucidated. Full article
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10 pages, 1758 KiB  
Article
Organometallic Iridium Complexes with Glucose Based Phosphite Ligands
by Maria R. Gonchar, Fedor S. Ninin, Dmitrii M. Mazur, Konstantin A. Lyssenko, Elena R. Milaeva and Alexey A. Nazarov
Inorganics 2023, 11(3), 124; https://doi.org/10.3390/inorganics11030124 - 15 Mar 2023
Viewed by 1004
Abstract
New organometallic iridium compounds with phosphorus modified glucose ligands containing isopropylidene protection group or bearing uracil, thymine, and 5-fluorouracil (3,5,6-bicyclophosphite-1,2-O-isopropylidene-α-d-glucofuranoside, 3,5,6-bicyclophosphite-1-β-D-glucofuranosyluracil, 3,5,6-bicyclophosphite-1-β-D-glucofuranosylthymine, 3,5,6-bicyclophosphite-1-β-D-glucofuranosyl-5-flurouracil) were prepared. The structure of the new complexes was confirmed by the spectroscopic technique (1H, 31 [...] Read more.
New organometallic iridium compounds with phosphorus modified glucose ligands containing isopropylidene protection group or bearing uracil, thymine, and 5-fluorouracil (3,5,6-bicyclophosphite-1,2-O-isopropylidene-α-d-glucofuranoside, 3,5,6-bicyclophosphite-1-β-D-glucofuranosyluracil, 3,5,6-bicyclophosphite-1-β-D-glucofuranosylthymine, 3,5,6-bicyclophosphite-1-β-D-glucofuranosyl-5-flurouracil) were prepared. The structure of the new complexes was confirmed by the spectroscopic technique (1H, 31P{1H} NMR) and mass spectrometry, and purity by elemental analysis. The molecular structure of the complex with the isopropylidene protection group was established by the X-ray analysis. The antiproliferative activity of the new iridium compounds was evaluated against several cancer cell lines of human origin, and all compounds showed low toxicity independent of the pyrimidine base nature, attached to the sugar unit. Full article
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10 pages, 1017 KiB  
Article
Palladium(II) and Platinum(II) Deprotonated Diaminocarbene Complexes Based on N-(2-Pyridyl)ureas with Oxadiazole Periphery
by Kirill K. Geyl, Svetlana O. Baykova, Pavel A. Andoskin, Vladimir V. Sharoyko, Anastasiya A. Eliseeva, Sergey V. Baykov, Konstantin N. Semenov and Vadim P. Boyarskiy
Inorganics 2022, 10(12), 247; https://doi.org/10.3390/inorganics10120247 - 07 Dec 2022
Cited by 4 | Viewed by 1213
Abstract
Metal mediated coupling of isocyanides with substituted N-(pyridine-2-yl) ureas was first used to incorporate privileged biological motifs into platinum metal complexes. We synthesized two palladium(II) and two platinum(II) cyclometallated species with oxadiazole cores. The compounds were isolated in good yields (61–73%) and [...] Read more.
Metal mediated coupling of isocyanides with substituted N-(pyridine-2-yl) ureas was first used to incorporate privileged biological motifs into platinum metal complexes. We synthesized two palladium(II) and two platinum(II) cyclometallated species with oxadiazole cores. The compounds were isolated in good yields (61–73%) and characterized by high-resolution mass spectrometry and 1H, 13C, and 195Pt NMR spectroscopies. The structures of three complexes were additionally elucidated by X-ray diffraction analysis. These complexes indeed showed cytotoxic activity. The species bearing the 1,3,4-oxadiazole moiety exhibit more potency than the ones with the 1,2,4-oxadiazole ring. Particularly, the cytotoxic effect of both 1,3,4-oxadiazole-based complexes towards T98G cells significantly exceeds the common antitumor metal-drug cisplatin. Full article
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10 pages, 1606 KiB  
Article
3′-Aminothiocyclohexanespiro-5′-hydantoin and Its Pt(II) Complex—Synthesis, Cytotoxicity and Xanthine Oxidase Inhibitory Activity
by Emiliya Cherneva, Mariyana Atanasova, Žaklina Šmelcerović, Katarina Tomović, Rossen Buyukliev, Andrija Šmelcerović and Adriana Bakalova
Inorganics 2022, 10(10), 175; https://doi.org/10.3390/inorganics10100175 - 20 Oct 2022
Cited by 1 | Viewed by 1298
Abstract
Herein, we report the synthesis of platinum(II) complex bearing 3′-aminothiocyclohexanespiro-5′-hydantoin as ligand. The complex was characterized by IR, NMR spectral analyses, elemental analyses and density functional theory (DFT) calculations. Cytotoxicity and inhibitory potential on xanthine oxidase (XO) were evaluated by performed docking calculations. [...] Read more.
Herein, we report the synthesis of platinum(II) complex bearing 3′-aminothiocyclohexanespiro-5′-hydantoin as ligand. The complex was characterized by IR, NMR spectral analyses, elemental analyses and density functional theory (DFT) calculations. Cytotoxicity and inhibitory potential on xanthine oxidase (XO) were evaluated by performed docking calculations. The cytotoxic activities of the 3′-aminothiocyclohexanespiro-5′-hydantoin (1), its Pt(II) complex (2), thiocyclohexanespiro-5′-hydantoin (3), and its platinum complex (4) were assessed against HL-60 and MDA-MB-231 cells in comparison with the antiproliferative activity of cisplatin as a referent. The ligands (1 and 3) did not exhibit in vitro antitumor efficacy on either of the human tumor cell lines. Complex 2 showed higher antitumor activity (IC50 = 42.1 ± 2.8 μM on HL-60 and 97.8 ± 7.5 μM against MDA-MB-231 cells) than complex 4 (IC50 = 89.6 ± 2.8 μM on HL-60 and 112.5 ± 4.2 μM in MDA-MB-231 cells). IC50 values of cisplatin as referent were 8.7 ± 2.4 μM on HL-60 and 31.6 ± 5.4 μM on MDA-MB-231 cell lines. The inhibitory activity of ligands and complexes against XO, evaluated in vitro, were compared with allopurinol (IC50 = 1.70 ± 0.51 μM) as standard inhibitor. The platinum(II) complexes (2 and 4) inhibited the activity of XO, with IC50 values 110.33 ± 26.38 μM and 115.45 ± 42.43 μM, respectively, while the ligands 1 and 3 did not show higher degrees of inhibition at concentrations lower than 150 μM. The inhibitory potential against XO might be a possible precedent resulting in improved profile and anticancer properties. Full article
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