Iridium piano stool complexes with activity against<i>S. aureus</i>and MRSA: it is past time to truly think outside of the box

DuChane, Christine M; Karpin, George W.; Ehrich, Marion; Falkinham, Joseph O.; Merola, Joseph S.

doi:10.1039/c9md00140a

Cited by 12 publications

(9 citation statements)

References 40 publications

(36 reference statements)

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“…Investigations into the cytotoxicity of the iridium Cp* diamine complexes were encouraging, with no toxicity observed against Vero or human embryonic kidney cell lines at concentrations at least 50 times higher than that of the minimum inhibitory concentrations. Additional in vivo toxicity screenings on a group of adult outbred white mice showed no detrimental side effects 14 days after administering a single IV dose (2.5 or 5 μg/kg), and a subsequent ICP-OES analysis found practically no iridium in the blood, heart, or lungs of the mice, with most of the iridium localized in the kidneys or excreted as urine …”

Section: Introductionmentioning

confidence: 68%

“…Additional in vivo toxicity screenings on a group of adult outbred white mice showed no detrimental side effects 14 days after administering a single IV dose (2.5 or 5 μg/kg), and a subsequent ICP-OES analysis found practically no iridium in the blood, heart, or lungs of the mice, with most of the iridium localized in the kidneys or excreted as urine. 21 In order to advance the rapidly growing interest in the biological properties of metal NHC complexes, in this article we report the synthesis, characterization, and antimicrobial activities of Rh III and Ir III piano-stool complexes featuring a series of Cp* R and NHC ligands (Figure 4, bottom). Since the antimicrobial properties of these particular complexes have been understudied up to this point, this work features a wide scope of Cp* R substituents and NHC ligands to further the understanding of structure−activity relationships across noblemetal piano-stool complexes.…”

Section: ■ Introductionmentioning

confidence: 99%

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Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes

et al. 2021

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A series of Rh III and Ir III piano-stool complexes of the form [(η 5 -Cp* R )M(NHC)Cl 2 ] was synthesized and characterized, including 12 X-ray crystallographic structures. The antimicrobial properties of these complexes were screened against a variety of microbes, with several achieving high activities, most notably against Mycobacterium smegmatis (MICs as low as 0.45 μM). In general, the Rh complexes were more potent than their Ir analogues, and activity increased with the hydrophobicity of the Cp* R and NHC ligands. Article pubs.acs.org/Organometallics

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Section: Introductionmentioning

confidence: 68%

Section: ■ Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes

et al. 2021

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“…Through ICP-OES it was shown that the iridium compounds were excreted efficiently through their urine and no iridium was detectable following sacrifice of the mice on day 14. No data on in vivo efficacy was reported in this study [102].…”

Section: Iridiummentioning

confidence: 82%

Metal Complexes, an Untapped Source of Antibiotic Potential?

2020

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With the widespread rise of antimicrobial resistance, most traditional sources for new drug compounds have been explored intensively for new classes of antibiotics. Meanwhile, metal complexes have long had only a niche presence in the medicinal chemistry landscape, despite some compounds, such as the anticancer drug cisplatin, having had a profound impact and still being used extensively in cancer treatments today. Indeed, metal complexes have been largely ignored for antibiotic development. This is surprising as metal compounds have access to unique modes of action and exist in a wider range of three-dimensional geometries than purely organic compounds. These properties make them interesting starting points for the development of new drugs. In this perspective article, the encouraging work that has been done on antimicrobial metal complexes, mainly over the last decade, is highlighted. Promising metal complexes, their activity profiles, and possible modes of action are discussed and issues that remain to be addressed are emphasized.Antibiotics 2020, 9, 90 2 of 24 Metal-containing compounds have played a small but seminal role in medicinal chemistry of throughout the 20th century. An arsenic-containing compound, Salvarsan, was discovered at the beginning of the century and became the first effective treatment of syphilis [9]. It was however the discovery of the anticancer drug cisplatin and its successors that really kickstarted the field of inorganic medicinal chemistry. Even today, platinum-based chemotherapeutics are still used in the majority of cancer treatments [10]. The gold-containing auranofin is an approved drug for the treatment of rheumatoid arthritis and is currently under investigation for its anticancer as well as antimicrobial properties [11][12][13][14][15][16]. Invigorated by these breakthrough successes, the field has expanded to many other elements in the last few decades, with complexes of titanium, iron, ruthenium, gallium, palladium, silver, gold, bismuth, and copper entering clinical trials [17][18][19][20][21][22]. The medicinal applications of these metal complexes range from anticancer to antimalaria over to neurodegenerative diseases. Strangely, antibacterial applications are remarkably sparse in this list and the number of literature reports on metal-based antimicrobials is dwarfed by the much more frequent publications on metal-based anticancer compounds. This is surprising as metals such as bismuth and silver have long been known to possess antibacterial properties. Some medicinal products are currently available. There are however a variety of products, such as silver-coated underwear, with a more dubious scientific basis. Nevertheless, the systematic evaluation of the antimicrobial properties of metal complexes has increased in pace over the last decade, with several reports highlighting the activity and potential modes of action of metal-based antibiotics. This perspective article will discuss the major discoveries in the non-traditional field of metal complex-based antibiotic co...

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“…Complex inactivation may stem from halide dissociation over time to give an inactive cationic or dicationic metal complex [55]. Salt supplementation, such as with NaCl or KCl, Alternatively, the complexes may act directly on the viral proteins of the virion.…”

Section: Discussionmentioning

confidence: 99%

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

Chuong

DuChane

Webb

et al. 2021

Viruses

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SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals. Our findings demonstrate that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(1,3-dicyclohexylimidazol-2-ylidene)Cl2 (complex 2) and Cp*Rh(dipivaloylmethanato)Cl (complex 4), have direct virucidal activity against SARS-CoV-2. Subsequent in vitro testing suggests that complex 4 is the more stable and effective complex and demonstrates that both 2 and 4 have low toxicity in Vero E6 and Calu-3 cells. The results presented here highlight the potential application of organometallic complexes as antivirals and support further investigation into their activity.

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Iridium piano stool complexes with activity againstS. aureusand MRSA: it is past time to truly think outside of the box

Abstract: Iridium based antimicrobial agents have shown efficacy against S. aureus, including MRSA, and appear to be safe in mice.

Cited by 12 publications

References 40 publications

Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes

Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes

Metal Complexes, an Untapped Source of Antibiotic Potential?

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

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Iridium piano stool complexes with activity againstS. aureusand MRSA: it is past time to truly think outside of the box

Abstract: Iridium based antimicrobial agents have shown efficacy against S. aureus, including MRSA, and appear to be safe in mice.

Cited by 12 publications

References 40 publications

Synthesis, Characterization, and Antimicrobial Activity of RhIII and IrIII N-Heterocyclic Carbene Piano-Stool Complexes

Synthesis, Characterization, and Antimicrobial Activity of RhIII and IrIII N-Heterocyclic Carbene Piano-Stool Complexes

Metal Complexes, an Untapped Source of Antibiotic Potential?

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

Contact Info

Product

Resources

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Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes

Synthesis, Characterization, and Antimicrobial Activity of Rh^III and Ir^III N-Heterocyclic Carbene Piano-Stool Complexes