(C^N^pz^C)Au^IIIcomplexes of acyclic carbene ligands: synthesis and anticancer properties

Abstract

A series of cyclometallated gold(iii) complexes supported by pyrazine-based (C^N^C)-type pincer ligands were synthesized via two different pathways. Nucleophilic attack on the isocyanide complex [(C^N^C)Au(C[triple bond, length as m-dash]NCHMe-2,6)]SbF (2) gave [(C^N^C)Au(ACC)]SbF complexes with aniline (4·SbF), adamantylamine (5), glycine ethyl ester (6), alanine methyl ester (7), valine methyl ester (8), phenylglycine methyl ester (9) and methionine methyl ester (10) substituents (ACC = acyclic carbene). The pathway via isocyanide insertion into gold-amide bonds was also investigated; e.g. the reaction of xylyl isocyanide with (C^N^C)AuNHPh followed by protonation with HBF·OEt gave the acyclic carbene complex 4·BF. To the best of our knowledge compounds 6-10 represent the first examples of gold(iii) acyclic carbene complexes bearing amino acid functions. The compounds provide a versatile platform for the study of the anti-proliferative properties of gold(iii) complexes. Tests against human adenoma-type lung cancer cells identified 5, 6, 7 and 10 as particularly promising and demonstrate the synthetic flexibility of acyclic carbene complexes and the potential of that class of compounds for anticancer applications. Compared to cisplatin, amino ester-containing ACC complexes showed improved selectivity for MCF-7 breast cancer cells over that for healthy fibroblasts.

Cyclometallated Au(iii) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies

“…However, this is in line with reports for other cyclometallated Au(III) complexes, 28,38 suggesting that in our case of mixed cyclometallated/DTC complexes, the inability to generate ROS is related to the cyclometallated ligand structure.…”

Gold(III) Complexes for Antitumor Applications: An Overview

“…Reactingn ucleophiles with an electrophilic isocyanide complex [(C^N^C)Au(CNÀR)] + leads to the formation of the corresponding acyclic carbene complexes of type 36,a ss hown in Figure 11.T he reactionh as been testedw ith success with amines and amino esters to generateaseries of complexes 36. [85] The compounds were tested against ap anel of cancer cells and showed higher activity than cisplatin against A549, MCF-7 and MDA-MB-231. However,t hesea cyclic carbene complexes provedm ore sensitive to reduction by GSH than the related complex 33 bearing ac yclic carbene ligand.S ince 36 did not induce overproduction of ROS, interference with the mitochondrial redox activity was ruled out as potential mechanism.…”

A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and Bioconjugated Complexes: Synthesis and Anticancer Potential

“…However, although that methodology was successful when using amino esters, the requirement to work under perfectly anhydrous conditions precluded the use of more elaborate biomolecules. Moreover, those acyclic carbene complexes were found to be much less stable toward GSH than cyclic NHC‐based complexes …”