Gold(I)-Phosphine-N-Heterocycles: Biological Activity and Specific (Ligand) Interactions on the C-Terminal HIVNCp7 Zinc Finger

This study reports the synthesis and characterization, through chemical analysis, 1H and 31P NMR spectroscopy, and mass spectrometry, of a series of linear triphenylphosphine gold(I) complexes with substituted N-heterocycle ligands [(PPh3)Au(I)(L)]+. The reaction of [(PPh3)Au(L)]+ (L = Cl– or substituted N-heterocyclic pyridine) with the C-terminal (Cys3His) finger of HIVNCp7 reveals evidence, through mass spectrometry (ESI-MS) and 31P NMR spectroscopy, of a long-lived {(PPh3)Au}-S-peptide species resulting from the displacement of the chloride or pyridine ligand by zinc-bound cysteine with concomitant displacement of Zn2+. In contrast, reactions with the Cys2His2 finger-3 of the Sp1 transcription factor show significantly reduced intensities of {(PPh3)Au} adducts.

These results suggest the possibility of systematic (electronic, steric) variations of the ‘carrier’ group PR3 and ‘leaving’ group L, as well as the nature of the zinc finger, in modulation of biological activity. The cytotoxicity, cell cycle signaling effects, and cellular accumulation of the series are also reported. All compounds display cytotoxicity in the micromolar range upon 96 h continuous exposure to human tumor cells. The results may have relevance for the reported inhibition of viral load in simian virus by the gold(I) drug auranofin.