Article

Synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic resistant bacteria

Center for Silver Therapeutics Research, Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
Dalton Transactions (Impact Factor: 4.2). 03/2012; 41(21):6500-6. DOI: 10.1039/c2dt00055e
Source: PubMed

ABSTRACT Silver N-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram-negative bacteria. A new series of three silver carbene complexes (SCCs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. The imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. The silver carbene complexes, SCC32, SCC33, and SCC34 were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These complexes proved highly efficacious with minimum inhibitory concentrations (MICs) ranging from 0.25 to 6 μg mL(-1). Overall, the complexes were effective against highly resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus (MRSA), weaponizable bacteria, such as Yersinia pestis, and pathogens found within the lungs of cystic fibrosis patients, such as Pseudomonas aeruginosa, Alcaligenes xylosoxidans, and Burkholderia gladioli. SCC33 and SCC34 also showed clinically relevant activity against a silver-resistant strain of Escherichia coli based on MIC testing.

Download full-text

Full-text

Available from: Carolyn Louise Cannon, Jan 15, 2015
3 Followers
 · 
227 Views
  • Source
    • "Although these systems have shown impressive anticancer activity, their principal drawback remains their limited solubility in water , which severely impairs the ability to administer these compounds systemically. Through the rational selection of substituents of the N-heterocycle, we have strived to synthesize the corresponding salts to have a higher solubility in water, while still maintaining the lipophilicity that is believed to contribute to their efficacy (Wright et al., 2012; Li et al., 2010; Youngs et al., 2012b, c). Additionally, by creating several analogs of an already effective lipophilic imidazolium salt, IC23 (Fig. 1), and observing their anticancer activity, we hope to begin to decipher the mechanism of action of these compounds. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-small-cell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents. Graphical Abstract
    Medicinal Chemistry Research 02/2015; 24(7). DOI:10.1007/s00044-015-1330-z · 1.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of cisplatin's antitumor activity in 1969 prompted the search for novel metal-containing complexes as potential anticancer drugs. Among these novel complexes, metal N-heterocyclic carbene (NHC) complexes have recently gained considerable attention because they perfectly fit prerequisites for efficient drug design and fast optimization. Moreover, most of them have shown higher cytotoxicity than cisplatin. This review describes the advances that have been achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes containing NHC ligands as antitumor agents. Their modes of action at the cellular lever are further discussed. All these initial achievements clearly demonstrate the great potential of metal-NHC complexes as antitumor agents.
    Chemical Society Reviews 11/2012; 42(2). DOI:10.1039/c2cs35314h · 30.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Six mono- and dinuclear N-heterocyclic carbene (NHC) silver complexes based on 1-[2-(pyrazol-1-yl)phenyl]imidazole have been synthesized and characterized by elemental analysis and NMR spectroscopy, and their structures have been confirmed by single crystal X-ray diffraction. The N-functionalized carbene ligands exhibit versatile coordination modes in these silver complexes. N-[2-(3,5-Dimethylpyrazol-1-yl)phenyl]-N-benzylimidazol-2-ylidene (L) acts as a monodentate ligand through the carbene carbon in mononuclear LAgCl. While in dinuclear L2Ag2(PF6)2 and L′2Ag2(PF6)2 (L′ = N-[2-(pyrazol-1-yl)phenyl]-N-benzylimidazol-2-ylidene), L and L′ act as bridging bidentate ligands through the pyrazolyl nitrogen and the carbene carbon atoms to two silver atoms. Though, these two silver atoms have different coordination environments. In the former, one silver atom coordinates with two carbene carbons, the other coordinates with two pyrazolyl nitrogen atoms. In the latter, each silver atom coordinates with one carbene carbon and one pyrazolyl nitrogen atom, respectively. A dinuclear macrocyclic structure is observed in m-xylyl bridging tetradentate bis-NHC complexes L2Ag2(BF4)2 and (L)CH2C6H4CH2(L)Ag2(BF4)2, in which the coordination mode of carbene ligands is similar with that in L2Ag2(PF6)2. Preliminary catalytic tests show that all these complexes exhibit highly effective catalytic activity in the three-component coupling reaction of alkyne, aldehyde and amine forming propargylamines.
    Journal of Organometallic Chemistry 02/2013; 726:1–8. DOI:10.1016/j.jorganchem.2012.12.008 · 2.17 Impact Factor
Show more