Inert cationic iridium(<scp>iii</scp>) complexes with phenanthroline-based ligands: application in antimicrobial inactivation of multidrug-resistant bacterial strains

Busto, Natalia; Vigueras, Gloria; Cutillas, Natalia; García, Begoña; Ruiz, José

doi:10.1039/d2dt00752e

Cited by 9 publications

(12 citation statements)

References 61 publications

(91 reference statements)

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“…Furthermore, no significant cytotoxicity was measured toward mammalian cells. Similar piano stool compounds [ 14 , 15 ] as well as iridium complexes with different scaffolds [ 16 , 17 , 18 , 19 ] were investigated by other groups with comparably promising results. Apart from iridium, gold, as a further example of a third-row transition metal, is popular and effective in antimicrobial research [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

et al. 2023

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In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics.

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Section: Introductionmentioning

confidence: 99%

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

et al. 2023

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“…GSH is found not only in eukaryotic cells but also can be found in Gram‐negative bacteria. However, with the exception of some Streptococcus and Enterococcus species, it is not found in Gram‐positive bacteria, where other thiol antioxidants are present in high concentrations [72] . We investigated whether the RuPNMPEA and IrPNMPEA complexes can act as catalysts for the oxidation of GSH to GSSG.…”

Section: Resultsmentioning

confidence: 99%

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine‐Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N‐Methylphenethylamine

Wojtala

Kozieł

Witwicki

et al. 2023

Chemistry A European J

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The phosphine ligand (Ph2PCH2N(CH3)(CH2)2Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N‐methylphenethylamine, was used to synthesize the half‐sandwich iridium(III) (Ir(η5‐Cp*)Cl2Ph2PCH2N(CH3)(CH2)2Ph, IrPNMPEA) and ruthenium(II) (Ru(η6‐p‐cymene)Cl2Ph2PCH2N(CH3)(CH2)2Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV‐Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram‐positive and Gram‐negative bacterial strains was examined, indicating that both complexes are selective towards Gram‐positive bacteria, e.g., Staphylococcus aureus, where the IrPNMPEA has been more bactericidal compared to RuPNMPEA. Additionally, the interactions of these compounds with various biomolecules, such as DNA (ctDNA, plasmid DNA, 9‐ethylguanine (9‐EtG), and 9‐methyladenine (9‐MeA)), nicotinamide adenine dinucleotide (NADH), glutathione (GSH), and ascorbic acid (Asc) were described. The results showed that both Ir(III) and Ru(II) complexes accelerate the oxidation process of NADH, GSH and Asc that appeared to occur by an electron transfer mechanism. Interestingly, only IrPNMPEA leads to the formation of various biomolecule adducts, which can explain its higher activity. Furthermore, RuPNMPEA and IrPNMPEA have been interacting with the DNA through weak noncovalent interactions.

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“…These results are expectable since the presence of the extra outer membrane in Gram-negative bacteria hinders drug internalization. 9 The type of metal centre and the bacterial uptake were not directly correlated with the antimicrobial activity (Table 1). Thus, while the iridium complex accumulates to a greater extent in S. aureus , the Rh complex shows greater activity in said bacterial strain.…”

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confidence: 98%

“…Organometallic complexes offer rich versatility for the design of new antimicrobial agents. [6][7][8][9][10] Unlike organic molecules, which have simple one-or two-dimensional shapes, metal compounds can access a great variety of three-dimensional structures, becoming ideal scaffolds for the development of new antibiotics. 7,11 Despite the fact that rhodium and iridium half-sandwich complexes have been less studied than other half-sandwich ruthenium complexes, 12 recent reports have highlighted the promising antibacterial properties of these compounds, particularly those featuring pentamethylcyclopentadienyl (Cp*), which provides stability and hydrophobicity, along with neutral chelating ligands [13][14][15] or carbene ligands.…”

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confidence: 99%

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Novel valproate half-sandwich rhodium and iridium conjugates to fight against multidrug-resistant Gram-positive bacteria

Marco¹,

Vigueras²,

Busto³

et al. 2023

Dalton Trans.

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Inert cationic iridium(iii) complexes with phenanthroline-based ligands: application in antimicrobial inactivation of multidrug-resistant bacterial strains

Abstract: The antimicrobial activity of a new series of heteroleptic iridium(III) complexes of the type [Ir(C^N)2(N^N)][PF6] (C^N = deprotonated 2-phenylbenzimidazole-κN, κC; N^N = phen (Ir1), dpq (Ir2), dppz (Ir3), dppn (Ir4),...

Cited by 9 publications

References 61 publications

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine‐Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N‐Methylphenethylamine

Novel valproate half-sandwich rhodium and iridium conjugates to fight against multidrug-resistant Gram-positive bacteria

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