title: Synthesis, characterization, and antimicrobial activity of silver carbene complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic resistant bacteria.
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.
authors.affiliation: Center for Silver Therapeutics Research, Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Wright
authors.forename: Parth N
authors.initials: PN
authors.lastname: Shah
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: McDonald
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shaeffer
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Wagers
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Justin
authors.initials: J
authors.lastname: Smolen
authors.forename: Jasur
authors.initials: J
authors.lastname: Tagaev
authors.forename: Claire A
authors.initials: CA
authors.lastname: Tessier
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cannon
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012834:Silver / Q000737:chemistry*
chemical_list: C574668:4,5,6,7-tetrachlorobenzimidazole; D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D009942:Organometallic Compounds; C030011:carbene; D012834:Silver; D008697:Methane