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 π‐type 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.
This tutorial review highlights key principles underpinning the design of selected metallodrugs to target specific biological macromolecules (DNA and proteins). The review commences with a descriptive overview of the eukaryotic...
A challenging synthesis yields a bis(carbene) AuI‐CNC pincer precursor complex that may be oxidized to a remarkably redox‐stable [AuIII(CNC)Cl]+ cation which shows significant cytotoxicity towards a breast cancer cell line. Electrophoresis, viscometry, and spectroscopic data suggest the likely mode of interaction of the compound with DNA involves partial intercalation, enabling it to potentially target both conventional and unconventional DNA species such as three‐way junctions (in silico data). More information can be found in the Full Paper by O. Q. Munro, D. I. Bezuidenhout, et al. (DOI: 10.1002/chem.202100598).
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