Abstract:
The syntheses of bis(triazolium)carbazole precursors
and their corresponding coinage metal (Au, Ag) complexes
are reported. For alkylated triazolium salts, di- or tetranuclear
complexes with bridging ligands were isolated, while the bis
(aryl) analogue afforded a bis(carbene) AuI
-CNC pincer
complex suitable for oxidation to the redox-stable [AuIII(CNC)
Cl]+ cation. Although the ligand salt and the [AuIII(CNC)Cl]+
complex were both notably cytotoxic toward the breast
cancer cell line MDA-MB-231, the AuIII complex was somewhat
more selective. Electrophoresis, viscometry, UV-vis, CD and LD
spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]+ complex
behaves as a partial DNA intercalator. In silico screening
indicated that the [AuIII(CNC)Cl]+ complex can target DNA
three-way junctions with good specificity, several other
regular B-DNA forms, and Z-DNA. Multiple hydrophobic πtype interactions involving T and A bases appear to be
important for B-form DNA binding, while phosphate O···Au
interactions evidently underpin Z-DNA binding. The CNC
ligand effectively stabilizes the AuIII ion, preventing reduction
in the presence of glutathione. Both the redox stability and
DNA affinity of the hit compound might be key factors
underpinning its cytotoxicity in vitro.
