학술논문

Synthesis from Caffeine of a Mixed N-Heterocyclic Carbene-Silver Acetate Complex Active against Resistant Respiratory Pathogens
Document Type
Article
Source
Journal of Medicinal Chemistry; November 2006, Vol. 49 Issue: 23 p6811-6818, 8p
Subject
Language
ISSN
00222623; 15204804
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 4was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol. Complex 4demonstrated antimicrobial activity against numerous resistant respiratory pathogens from the lungs of cystic fibrosis (CF) patients including members of the Burkholderia cepaciacomplex 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.