Synthesis and crystallographic characterization of multi-donor N-heterocyclic carbene chelating ligands and their silver complexes: Potential use in pharmaceuticals Jered C. Garrison, Claire A. Tessier, Wiley J. Youngs * Department of Chemistry, The University of Akron, Akron, OH 44325, USA Received 22 June 2005; received in revised form 27 July 2005; accepted 27 July 2005 Available online 15 September 2005 Abstract The potential for N-heterocyclic carbenes (NHCs) to be used as novel chelating ligands for bio-inorganic pharmaceuticals is dis- cussed. In this paper, we design, synthesize and characterize two NHC precursors, 6 and 7, that we believe have potential for use as metal chelators for pharmaceuticals. The NHC precursors are composed of imidazolium and pyridine rings that would form mixed donor NHCs upon metallation with medicinally relevant metals. The exploration of the silver chemistry of 6 yielded the dimeric silver NHC complex 8[BPh 4 ] 2 . The study of the silver chemistry of 7 gave 9[1/3(Ag 4 Br 7 )] and 10[NO 3 ] 3 . Complex 9[1/3(Ag 4 Br 7 )] appears to be a silver biscarbene charge balanced by a silver bromide anionic cluster. Complex 10[NO 3 ] 3 is a trinuclear silver cluster that is stabilized by NHCs and pyridine rings. Silver NHCs have shown themselves to be excellent transmetallation agents for access to other metal NHC systems. It is envisioned that the silver NHCs 8[BPh 4 ] 2 , 9[1/3(Ag 4 Br 7 )] and 10[NO 3 ] 3 will readily transfer to medicinally relevant metals, such 105 Rh. Ó 2005 Elsevier B.V. All rights reserved. Keywords: Silver N-heterocyclic carbenes; Pharmaceuticals; Imidazolium salts; Mixed donor ligands; X-ray; Trinuclear silver cluster 1. Introduction The synthesis of metal N-heterocyclic carbene (NHC) complexes from imidazolium salts were first reported by O ¨ fele and Wanzlink in 1968 [1]. Lappert and co-work- ers, a decade later, expanded on this work by synthesiz- ing metal N-heterocyclic carbene complexes from electron rich olefins [2]. However, it was not until the isolation of the free carbene, in 1991, by Arduengo and co-workers that N-heterocyclic carbenes received a great deal of interest [3]. Since then, the study of N-het- erocyclic carbenes as novel ligands for the synthesis of organometallic compounds has been an area of intense research [4]. This has been particularly true for the use of NHCs as novel ligands for catalytic functions. The formation of silver N-heterocyclic carbene com- plexes can be accomplished by the generation of the free carbene and subsequent reaction of the free carbene with a metal reagent [5]. However, some ligand systems have been found to be sensitive to the harsh conditions required to generate the free carbene [5b,5c,6]. Also, the synthesis of metal NHCs by the free carbene method re- quires the use of anaerobic conditions. The reports of in situ formation of silver NHC complexes from a vari- ety of silver reagents led to the convenient synthesis of silver NHCs in aerobic conditions [7]. However, it was not until the reported transmetallation of silver NHCs to other important metal NHC systems by Lin and col- leagues that silver NHC chemistry took on an important role in the exploration of other metal NHC systems [7b]. The incorporation of other donor groups, particularly 0022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jorganchem.2005.07.102 * Corresponding author. Tel.: +1 330 972 5362/7914; fax: +1 330 972 7370. E-mail address: youngs@uakron.edu (W.J. Youngs). Journal of Organometallic Chemistry 690 (2005) 6008–6020 www.elsevier.com/locate/jorganchem