Dinuclear Au(i) N-heterocyclic carbene complexes derived from unsymmetrical azolium cyclophane salts: potential probes for live cell imaging applications

Abstract

We have synthesized a new series of azolium cyclophanes and used them as precursors of inherently luminescent dinuclear Au(i)-N-heterocyclic carbene (NHC) complexes. The azolium cyclophanes contained two azolium groups (either imidazolium or benzimidazolium), an o-xylyl group, and an alkyl linker chain (either C2, C3 or C4). All of the azolium cyclophanes were characterised by X-ray diffraction studies and VT NMR studies, and all were fluxional in solution on the NMR timescale. The C3- and C4-linked azolium cyclophanes served as precursors of Au2L2(2+) complexes (L is a cyclophane bis(NHC) ligand). Due to the unsymmetrical nature of the azolium cyclophanes, the Au2L2(2+) complexes each existed as cis and trans isomers. X-ray diffraction studies showed that the Au2L2(2+) complexes had short intramolecular AuAu distances, in the range 2.9-3.3 Å, suggestive of an aurophilic attraction, presumably as a consequence of the geometrical constraints imposed by the cyclophane bis(NHC) ligands. The complexes having the shortest AuAu distances (i.e., those based on C3-linked cyclophanes) exhibited intense luminescence in solution. The uptake of one of the dinuclear Au-NHC complexes by tumorigenic cells, and its subsequent distribution and toxicity in the cells, was monitored by luminescence microscopy over 6 h and proliferation measurements, respectively.

Formation of Dinuclear AuII and AuI/AuIII Mixed‐Valence Complexes is Directed by Structural Constraints Imposed by Cyclophane‐NHC Ligands

“…The coordination sphere of each Au centre is completed by two carbene carbons, a halide (X – ) and another Au atom, with the X–Au–Au–X arrangement being approximately linear. The cyclophane‐NHC framework is arranged about the Au–Au core in a similar fashion to that seen in the dinuclear Au I – ortho ‐cyclophane complex 1 2+ ,[6b] but for 2 2+ , 3 2+ and 4 2+ the Au ··· Au distance is now much shorter, at around 2.63 Å. This short Au ··· Au distance is within the range observed[5c], [5e], for a variety of complexes containing an Au II –Au II core held in place by one or two bridging ligands (e.g., see Table S1 in the Supporting Information).…”

“…NHC systems are convenient scaffolds for constructing dinuclear Au complexes , . Tubaro and Hemmert[6i], [6j] and their co‐workers have explored the reactions of dinuclear Au I –NHC complexes of the type [ A ] (Scheme ) with halogens and related oxidising agents. The products of these reactions (Scheme ) contained an Au I and an Au III centre (type [ B ]), two Au II centres (type [ C ]) or two Au III centres (type [ D ]).…”

“…The bis(NHC) ligands in those studies were conformationally labile and so could accommodate a range of intramolecular Au ··· Au distances. For example, in the case in which the linking group was a propylene chain,[6c] the bis(NHC) ligand could accommodate a short Au ··· Au distance and form an Au II /Au II complex, or it could accommodate a longer Au ··· Au distance and form an Au III /Au III complex. Similarly, with an o ‐xylylene linking group in the bis(NHC) ligand,[6h] Au II /Au II , Au III /Au III and Au I /Au III complexes could be formed.…”

“…The cyclophane framework restricts the conformational mobility of the NHC moieties, so that the cyclophane‐bis(NHC) ligands can only support a restricted range of Au ··· Au distances. [3b], [6a], [6b]…”

Synthesis and Biological Studies on Dinuclear Gold(I) Complexes with Di-(N-Heterocyclic Carbene) Ligands Functionalized with Carbohydrates

“…The performances of the dinuclear complexes, in terms of both activity and selectivity, were compared to their corresponding mononuclear counterparts and to dinuclear complexes not having carbohydrate-functionalized NHCs. Dinuclear Au(I) complexes with one or two bridging diNHC carbene ligands were reported to present anticancer properties, acting by inhibiting the thioredoxin reductase TrxR or by leading to mitochondria-induced apoptosis [24][25][26][27][28][29][30][31].…”