Cyclometalated Gold(III) Complexes Bearing DACH Ligands

Sailajah Gukathasan, Sean Parkin, Samuel G. Awuah

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37 Scopus citations

Abstract

The synthesis of a novel class of cyclometalated gold(III) complexes supported by benzoylpyridine, benzylpyridine, and (1R,2R)-(+)-1,2-diaminocyclohexane (DACH) ligands, along with their crystal structures, is reported. These compounds provide a new scaffold to investigate biological properties of gold(III) complexes. The six complexes were prepared and characterized, following reactions of (C,N) cyclometalated gold(III) scaffolds, [Au(C-N)Cl2] with DACH, which yielded a new series of cyclometaled gold(III), 3-5, of the type [Au(C^NH)(DACH)2]+ and the nitrogen-substituted cyclometalated Au(III), 6-8, of the type [Au(C^N)(DACH)]2+. Antiproliferative activity of these complexes in a panel of cancer cells showed promising results with IC50 in the micromolar range and selectivity over normal epithelial cells, MRC5. Whereas 8 shows minimal interaction with superhelical DNA except at high gold concentrations of 500 μM, complex 5 does not show interaction even at 1000 μM. The complexes display significant uptake in OVCAR8 cancer cells within 200-1200 pmol/million cells with the exception of complex 4. Differential cellular uptake was observed for the complexes; for example, while 3 and 8 display significant uptake, 4 showed minimal uptake. The compounds proved to be stable under physiological conditions and were minimally affected by either glutathione or sodium ascorbate. Cell cycle studies reveal a G1 arrest induced by representative complexes. The results reveal that enhanced Au(III) stabilization promoted by combined cyclometalated and DACH ligands may offer ligand tuning insights for novel anticancer drug design.

Original languageEnglish
Pages (from-to)9326-9340
Number of pages15
JournalInorganic Chemistry
Volume58
Issue number14
DOIs
StatePublished - Jul 15 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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