jm060711t_si_001.pdf (223.8 kB)
Synthesis from Caffeine of a Mixed N-Heterocyclic Carbene−Silver Acetate Complex Active against Resistant Respiratory Pathogens
journal contribution
posted on 2006-11-16, 00:00 authored by Aysegul Kascatan-Nebioglu, Abdulkareem Melaiye, Khadijah Hindi, Semih Durmus, Matthew J. Panzner, Lisa A. Hogue, Rebekah J. Mallett, Christine E. Hovis, Marvin Coughenour, Seth D. Crosby, Amy Milsted, Daniel L. Ely, Claire A. Tessier, Carolyn L. Cannon, Wiley J. YoungsThe 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.