Internal and External Influences on Stability and Ligand Exchange Reactions in Bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) Complexes.

Sina Katharina Goetzfried,Ronald Gust,Sophie Marie Charlotte Koenig,Caroline Marie Gallati

doi:10.1021/acs.inorgchem.1c00325

Abstract

The ligand scrambling reaction of gold(I) complexes is a phenomenon occurring primarily in L–AuI–X (L = phosphine, N-heterocyclic carbene (NHC), and thiol; X = halide and thiol) complexes and has been observed among others for e.g., the bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) complex (7a), which underwent ligand rearrangement in aqueous solutions. In this study, we investigated the influence of substituents on the 4-aryl ring of the related (NHC)AuIBr complexes (1a–9a) in terms of the conversion to the [(NHC)2AuI]+ (1b–9b) and [(NHC)2AuIIIBr2]+ (1c–9c) species. Furthermore, the influence of external factors such as solvent, temperature, concentration, and presence of halides (Cl–, Br–, and I–) or hydroxyl ions was studied to gain a deeper understanding of the ligand rearrangement reaction. The substituent on the 4-aryl ring has a marginal impact on the scrambling reaction. Out of the investigated organic solvents (dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethanol (EtOH), methanol (MeOH), and acetonitrile (ACN)), only ACN separates single complex molecules. In all other solvents, relatively stable ((NHC)AuIBr)2 dimers are present. The addition of water to ACN solutions forces the formation of such dimeric units, starting the transformation to [(NHC)2AuI]+ and [(NHC)2AuIIIBr2]+. The rate-determining step is the release of Br– from a T-shape intermediate because an excess of KBr terminates this reaction. Furthermore, it is obvious that only single molecules react with halides. The aurophilic interactions between two (NHC)AuIBr molecules are too strong in the presence of water and largely impeded reaction with halides. As a single molecule, the reaction with Cl– (e.g., in a 0.9% NaCl solution) is notable, while I– even leads to a fast and quantitative conversion to (NHC)AuII and finally to [(NHC)2AuI]+.

Highlights

The mobile phase consisted of ACN and water with 0.1% trifluoroacetic acid (TFA)
The peaks were assigned by the analysis of their UV−vis spectra or comparison with synthesized reference compounds ((NHC)AuIX; X = I: 8d, X = Cl: 8e, X = OH: 8f).[41]
Halide, N-heterocyclic carbene (NHC)) derivatives in more detail, immediately after dissolution in the cell culture medium and during the first 12 h of incubation, which is relevant to cellular accumulation. Such investigations will be part of a forthcoming paper. In this structure−activity relationship study, we investigated internal and external parameters essential for the ligand exchange reactions in bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]

Summary

Introduction

Ligand exchange is used to coordinate metallodrugs, e.g., gold complexes, to carrier ligands for high accumulation within cells.[18,20−23]. The stability of metal complexes depends on the central ion and the used ligands. Are less stable than those of transition metal ions and exchange the ligands rapidly. Gold(I) complexes are susceptible to undergo rearrangement reactions.[4,6−8] Ligands can be categorized as carrier ligands or leaving groups, depending on their binding strength to the metal. Resulting (NHC)gold(I) complexes are promising candidates for the application in medicinal and inorganic chemistry because of their anticancer activity[26−29] as well as luminescence[30−32] and catalytic[33] properties

Results

Discussion

Conclusion