A Conformationally Restricted Gold(III) Complex Elicits Antiproliferative Activity in Cancer Cells

Abstract

Diamine ligands are effective structural scaffolds for tuning the reactivity of transition-metal complexes for catalytic, materials, and phosphorescent applications and have been leveraged for biological use. In this work, we report the synthesis and characterization of a novel class of cyclometalated [C^N] Au(III) complexes bearing secondary diamines including a norbornane backbone, (2R,3S)-N 2 ,N 3 -dibenzylbicyclo[2.2.1]heptane-2,3-diamine, or a cyclohexane backbone, (1R,2R)-N 1 ,N 2dibenzylcyclohexane-1,2-diamine. X-ray crystallography confirms the square-planar geometry and chirality at nitrogen. The electronic character of the conformationally restricted norbornane backbone influences the electrochemical behavior with redox potentials of −0.8 to −1.1 V, atypical for Au(III) complexes. These compounds demonstrate promising anticancer activity, particularly, complex 1, which bears a benzylpyridine organogold framework, and supported by the bicyclic conformationally restricted diaminonorbornane, shows good potency in A2780 cells. We further show that a cellular response to 1 evokes reactive oxygen species (ROS) production and does not induce mitochondrial dysfunction. This class of complexes provides significant stability and reactivity for different applications in protein modification, catalysis, and therapeutics.

Chiral nanomaterials in tissue engineering

“…188,189 Chiral nanomaterials, with their unique ability to modulate enantiospecific cell behaviour may be the key to addressing these unresolved challenges in tissue engineering. 190,191…”