Synthesis and characterization of Au(I) and Au(III) complexes containing N-heterocyclic ligands derived from amino acids Mario A. Reynoso-Esparza a , Irma I. Rangel-Salas a , A. Aarón Peregrina-Lucano a , José G. Alvarado-Rodríguez b , Fernando A. López-Dellamary-Toral c , Ricardo Manríquez-González c , María L. Espinosa-Macías a , Sara A. Cortes-Llamas a,⇑ a Departamento de Química y Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán #1421, esq. Olímpica, C.P. 44430 Guadalajara, Jalisco, Mexico b Universidad Autónoma del Estado de Hidalgo, Unidad Universitaria, km 4.5 Carretera Pachuca-Tulancingo, C.P. 42184 Mineral de la Reforma, Hidalgo, Mexico c Departamento de Madera, Celulosa y Papel, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Km 15.5 de la Carretera Guadalajara-Nogales, C.P. 45220 Zapopan, Jalisco, Mexico article info Article history: Received 20 March 2014 Accepted 9 July 2014 Available online 16 July 2014 Keywords: NHC ligand Gold Water solubility Carbene Amino acids abstract A series of [Au(NHC) 2 ](1a–4a) complexes supported by NHC ligands derived from glycine, alanine, methionine and phenylalanine (1–4 respectively) were prepared via a direct transmetalation reaction of their respective silver complexes. The Au complexes were characterized by ESI-MS and NMR spectros- copy in solution. These compounds exhibit instability when the solvent is removed; they displayed a strong tendency to form colored solutions in the order 4a > 3a > 2a > 1a, which is associated with gold nanoparticles. 1a and 2a undergo oxidative addition of elemental bromine, yielding [Au(NHC) 2 Br 2 ] (1b) for 1a and a mixture of [Au(NHC) 2 Br 2 ](2b) and [Au(NHC)Br 3 ](2c) for 2a. 2b and 2c were character- ized by single crystal X-ray diffraction. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Water can be considered the ideal solvent for homogeneous catalysis [1]. It is a non-toxic, economical and environmentally friendly solvent. Consequently, there has been an intensive search for water-soluble catalytic systems; [2] in this regard, ligands play a critical role to stabilize metal centers in water. On the other hand, N-heterocyclic carbene ligands (NHC) are excellent r- donors that are capable of stabilizing a large number of organometallic com- pounds; [3–5] the metal–carbon bond in NHC complexes is suffi- ciently strong that many of these compounds are not air or moisture sensitive and can even be synthesized in an aqueous med- ium [6]. In particular, Au-NHC complexes have emerged as excellent catalysts [7,8], and efficient agents in medical applications such as antitumor metallodrugs [9–12]. To fine-tune the lipophilic/hydro- philic character of the complexes, substituents attached to the imidazolium salt precursor, such as carboxylate [6], amide [13], ester [14], and sulfonate [15,16] groups have been studied. A strategy for preparing water soluble imidazolium salts precur- sors has been the use of a-amino acids which are inexpensive starting materials and water soluble; [17] furthermore they possess chiral centers, which open the possibility to obtain chiral ligands. For example, Kühl et al. prepared imidazolium zwitterions from a- amino acids; [18] these ligands possess wing-tip groups with car- boxylate substituents in the a-position of the wing-tip group, which favors the water solubility. Despite the attractive features of these ligands, there are few NHC-complexes with this sort of ligands [19,20]. To obtain further information on the structure and stability of water-soluble gold complexes, which have potential applications in green chemistry and are compatible with physiological media, we decided to explore the synthesis of Au(I) and Au(III) complexes sup- ported by NHC ligands derived from amino acids. 2. Results and discussion Following the original procedure patented by Arduengo [21], we attempted the synthesis of N,N ´ -disubstituted symmetric imi- dazolium zwitterions by a one-pot condensation between glyoxal, 2 equiv. of amino acid (glycine, L-alanine, L-methionine and L -phen- ylalanine for 1, 2, 3 and 4, respectively) and 1 equiv. of paraformal- dehyde in the presence of hydrochloric acid [18]. This procedure produced the desirable compounds in low yields with dark-brown impurities. However, when acetic acid was used instead of hydro- chloric acid, compounds 1–4 were obtained in good yields (Scheme 1) [22]. http://dx.doi.org/10.1016/j.poly.2014.07.014 0277-5387/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: sara.cortes@cucei.udg.mx (S.A. Cortes-Llamas). Polyhedron 81 (2014) 564–571 Contents lists available at ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly