Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens.
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.
Kascatan-Nebioglu
Aysegul
A
Department of Chemistry, University of Akron, Akron, Ohio 44325-3601, USA.
Melaiye
Abdulkareem
A
Hindi
Khadijah
K
Durmus
Semih
S
Panzner
Matthew J
MJ
Hogue
Lisa A
LA
Mallett
Rebekah J
RJ
Hovis
Christine E
CE
Coughenour
Marvin
M
Crosby
Seth D
SD
Milsted
Amy
A
Ely
Daniel L
DL
Tessier
Claire A
CA
Cannon
Carolyn L
CL
Youngs
Wiley J
WJ
D000085:Acetates / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002110:Caffeine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D003550:Cystic Fibrosis / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D025141:Drug Resistance, Fungal; D015870:Gene Expression / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000382:microbiology*; D018030:Silver Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
C516223:(1,3,7,9-tetramethylxanthine-8-ylidene)silver acetate; D000085:Acetates; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009942:Organometallic Compounds; D018030:Silver Compounds; C103100:silver acetate; D002110:Caffeine