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Exploring the Reactivity and Biological Effects of Heteroleptic N‐Heterocyclic Carbene Gold(I)‐Alkynyl Complexes
Author(s) -
Oberkofler Jens,
Aikman Brech,
Bonsignore Riccardo,
Pöthig Alexander,
Platts James,
Casini Angela,
Kühn Fritz E.
Publication year - 2020
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201901043
Subject(s) - chemistry , reactivity (psychology) , steric effects , carbene , ligand (biochemistry) , dissociation (chemistry) , medicinal chemistry , stereochemistry , nuclear magnetic resonance spectroscopy , photochemistry , combinatorial chemistry , organic chemistry , catalysis , medicine , biochemistry , alternative medicine , receptor , pathology
With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic Au I complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3‐dihydroimidazolylidene) were synthesized and characterized by 1 H and 13 C NMR and elemental analysis, and in some cases also by X‐ray diffraction. The compounds were all stable in H 2 O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand‐substitution reactions. 1 H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the case of the benzimidazolylidene series also dissociation of the NHC ligand could be observed. DFT calculations suggest that, depending on the steric hindrance exerted by both the NHC wingtip groups and the alkynyl substituents, the reaction can proceed either via a π‐stabilized intermediate or with the alkynyl ligand remaining purely σ‐coordinated to the Au I center until completely dissociated. The most stable compounds in PBS buffer (pH 7.4), as assessed by UV‐Visible spectrophotometry, were further investigated for their ability to stabilize G4 DNA by FRET DNA melting assay, showing only moderate activity. Moreover, two derivatives were tested in vitro for their anticancer activities in three different human cancer cell lines and showed cytotoxicity in the low micromolar range.