Coordination Chemistry Reviews 251 (2007) 884–895 N-Heterocyclic carbene–silver complexes: A new class of antibiotics Aysegul Kascatan-Nebioglu a , Matthew J. Panzner a , Claire A. Tessier a , Carolyn L. Cannon b , Wiley J. Youngs a,∗ a Department of Chemistry, University of Akron, Akron, OH 44325-3601, United States b Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States Received 1 May 2006; accepted 23 August 2006 Available online 7 September 2006 Contents 1. Introduction ............................................................................................................ 884 2. The use of silver compounds as antimicrobials ............................................................................. 886 2.1. Background on silver antimicrobials ................................................................................ 886 2.2. Mechanism of action and toxicity of silver ........................................................................... 886 3. Synthesis and the antimicrobial properties of silver–NHC complexes ......................................................... 887 3.1. Pyridine linked pincer NHC–silver complexes ....................................................................... 887 3.2. Silver–NHC complexes derived from xanthines ...................................................................... 890 4. Conclusions ............................................................................................................ 893 Acknowledgements ..................................................................................................... 893 References ............................................................................................................. 894 Abstract N-Heterocyclic carbene (NHC)–silver complexes were synthesized from pyridine linked pincer ligands and methylated caffeine. Pincer NHC–silver complexes were found to have more potent antimicrobial activity than the conventionally used silver antimicrobials. Encapsula- tion of a gem-diol pincer NHC–silver complex in a polymer mat demonstrated a promising method for the sustained delivery of silver ions in wound care applications. An NHC precursor derived from caffeine was found to have a low toxicity and the resulting silver complex showed encouraging antimicrobial activity against numerous pathogens including resistant organisms isolated from the lungs of patients with cystic fibro- sis (CF). Bacteria studied included members of the Burkholderia cepacia complex, which cause significant morbidity and mortality in infected CF patients. This review explores this newly growing area, focusing on the synthesis from pincer and xanthine ligands of new silver–NHC complexes and their antimicrobial activities. © 2006 Elsevier B.V. All rights reserved. Keywords: N-Heterocyclic carbene; Silver; Antimicrobial; Encapsulation; Caffeine; Cystic fibrosis 1. Introduction N-Heterocyclic carbenes (NHCs), are cyclic carbenes (Fig. 1) that are usually derived from the deprotonation of imidazolium salts. NHC chemistry was first investigated by Wanzlick et al. [1] in the early 1960s leading to the synthesis of the first NHC tran- sition metal complexes of chromium and mercury by ¨ Ofele [2] and Wanzlick and Sch¨ onherr [3] in 1968. The following decades ∗ Corresponding author. Tel.: +1 330 972 5362; fax: +1 330 972 7370. E-mail address: youngs@uakron.edu (W.J. Youngs). saw limited activity in this area, the most notable by Lappert and co-workers who synthesized several NHC–metal complexes from electron-rich olefins [4]. The isolation of the first stable NHC, 1,3-diadmantylimidazol-2-ylidene, by Arduengo et al. [5] was a breakthrough and lead to significant interest in this field of chemistry. The coordination chemistry of NHC–metal com- plexes continues to be actively studied, particularly for catalytic applications [6]. NHCs are strong nucleophiles and bind to both main group and transition metals often with greater stability than phosphines [6]. The carbene carbon atom of NHCs is stabilized by the p  –p  electron donation of the two adjacent nitrogen atoms accounting 0010-8545/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ccr.2006.08.019