Abstract
The bis(N-heterocyclic carbene) (NHC) silver complex, 3, with a methyl carbonate anion was formed from the reaction of the iodide salt of methylated caffeine, 1, with silver (I) oxide in methanol. Attempts to crystallize this complex from a mixture of common alcohols and ethyl acetate led to the formation of an NHC-silver acetate complex, 4. The more direct synthesis of 4 was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol. Complex 4 demonstrated antimicrobial activity against numerous resistant respiratory pathogens from the lungs of cystic fibrosis (CF) patients including members of the Burkholderia cepacia complex that cause a high rate of mortality in patients with cystic fibrosis (CF). Application of this NHC silver complex to primary cultures of murine respiratory epithelial cells followed by microarray analysis showed minimal gene expression changes at the concentrations effective against respiratory pathogens. Furthermore, methylated caffeine without silver showed some antibacterial and antifungal activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetates / chemistry*
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology
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Caffeine / analogs & derivatives*
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Caffeine / chemical synthesis
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Caffeine / chemistry*
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Caffeine / pharmacology
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Cells, Cultured
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Crystallography, X-Ray
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Cystic Fibrosis / microbiology
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Drug Resistance, Bacterial
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Drug Resistance, Fungal
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Gene Expression / drug effects
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Gram-Negative Bacteria / drug effects
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Gram-Negative Bacteria / isolation & purification
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Gram-Positive Bacteria / drug effects
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Gram-Positive Bacteria / isolation & purification
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Humans
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Methylation
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Mice
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Mice, Inbred C57BL
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Microbial Sensitivity Tests
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Molecular Structure
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Organometallic Compounds / chemical synthesis*
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Organometallic Compounds / chemistry
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Organometallic Compounds / pharmacology
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Respiratory Mucosa / cytology
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Respiratory Mucosa / drug effects
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Respiratory Mucosa / metabolism
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Respiratory Tract Infections / microbiology*
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Silver Compounds / chemistry*
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Structure-Activity Relationship
Substances
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(1,3,7,9-tetramethylxanthine-8-ylidene)silver acetate
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Acetates
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Anti-Bacterial Agents
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Antifungal Agents
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Organometallic Compounds
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Silver Compounds
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silver acetate
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Caffeine