biostudies-literatureGukathasan SDivision of ChemistryNational Cancer InstituteNCI NIH HHSNIGMS NIH HHS13118-13129https://www.ebi.ac.uk/biostudies/studies/S-EPMC11268950biostudies-literatureUnknown62(32)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, (2<i>R</i>,3<i>S</i>)-<i>N</i>²,<i>N</i>³-dibenzylbicyclo[2.2.1]heptane-2,3-diamine, or a cyclohexane backbone, (1<i>R</i>,2<i>R</i>)-<i>N</i>¹,<i>N</i>²-dibenzylcyclohexane-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 <b>1</b>, 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 <b>1</b> 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.Inorganic chemistryA Conformationally Restricted Gold(III) Complex Elicits Antiproliferative Activity in Cancer Cells.PMC11268950P30 CA177558CHE-2203559R01CA258421- 01P20 GM130456R01 CA258421Grossman RBAwuah SGSaryazdi SGukathasan SParkin SRatliff LObisesan OAfalseA Conformationally Restricted Gold(III) Complex Elicits Antiproliferative Activity in Cancer Cells.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, (2<i>R</i>,3<i>S</i>)-<i>N</i>²,<i>N</i>³-dibenzylbicyclo[2.2.1]heptane-2,3-diamine, or a cyclohexane backbone, (1<i>R</i>,2<i>R</i>)-<i>N</i>¹,<i>N</i>²-dibenzylcyclohexane-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 <b>1</b>, 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 <b>1</b> 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.2023-01-01T00:00:00Z2023 Aug2025-04-19T11:14:27.517Z2025-04-19T11:14:27.517ZS-EPMC112689503753067210.1021/acs.inorgchem.3c02066