Abstract:
Metal-based compounds featuring bioactive ligands have been widely used in a variety
of treatments such as chemotherapeutics. One of the notable ligand classes are Nheterocyclic
carbenes (NHCs) which can coordinate to a metal centre forming
anticancer metal–NHC complexes. To track them in cells, metal–NHC complexes can
be functionalised with a fluorescent moiety as an attractive design feature. For this
purpose, pro-carbenes featuring anthracenyl groups were prepared to form metal–
NHC compounds with the methyl-, pyridyl- or triazolyl-functionalised NHC ligand
potentially acting as mono- or bidentate ligands.
An extensive series of MII/III(cym/Cp*)(NHC) complexes (M = Ru, Os, Rh, Ir) was
synthesised and characterised. Some of the reactions of the pro-carbenes with
[Rh(Cp*)Cl2]2 resulted in the formation of unexpected structures. Intramolecular C–C
bond formation between the Cp* and anthracenyl groups with additional auxiliary
interactions between the Rh centre and anthracenyl moieties was observed, which
yielded polydentate ligands, i.e., hepta- and nonadentate ligand systems. The reaction
mechanism involves formation of a tetramethylfulvene complex via deprotonation of a
Cp* methyl group followed by metallocycloaddition and extraction of a chlorido ligand.
Some Rh–C interactions were extremely weak and could be easily displaced by
stronger electron donors such as 1,3,5-triaza-7-phosphaadamantane (pta). The
anticancer activity of the compounds in terms of in vitro cytotoxic activity against
different human cancer cell lines and cell morphology was investigated. The
complexes with monodentate NHC ligands were found to be cytotoxic with 50%
inhibitory concentrations (IC50) values in the low micromolar range, while the
complexes with C,N-chelating ligands and the Rh complexes with its nonadentately
coordinated ligand were found to exhibit greater activity with a slight decrease in the
IC50 values. The anticancer activity studies of the compounds were complemented by
experiments on the interactions of selected complexes with biomolecules amino acids
and DNA to identify biomolecular interaction potential. The reactions with the small
biomolecules proceeded quickly and resulted in the formation of adducts by
undergoing chlorido ligand exchange. A protein crystallographic study on the
interaction with hen egg white lysozyme revealed that the complex bound to L-aspartic
acid along with dissociation of the p-cymene ligand. These properties of the complexes
make them possible candidates for further development of anticancer drugs.