title: Targeting Antioxidant Pathways with FerrocenylatedN-Heterocyclic Carbene Supported Gold(I) Complexes in A549 Lung Cancer Cells.
abstract: Ferrocene containingN-heterocyclic carbene (NHC) ligated gold(I) complexes of the type [Au(NHC)2]+were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(I) chloride (5) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(I) chloride (6) revealed a quasi-liner geometry around the gold(I) centers, (i.e., the C-Au-C bond angle were measured to be ~177° and all the Au-Ccarbenebonds distances were in the range of 2.00 (7) - 2.03 (1) Å). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to amount of ferrocene contained within the [Au(NHC)2]+complexes (IC50of6 < 5 <bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(I) chloride (4)). Complexes4-6were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increase chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that6induces endoplasmic reticulum stress response pathways as a result of ROS increase.
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, Georgia, 30460, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Arambula
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, Georgia, 30460, USA.
authors.forename: R
authors.initials: R
authors.lastname: McCall
authors.affiliation: Department of Chemistry, 3261 West State Road, St. Bonaventure University, New York, 14778.
authors.forename: K J
authors.initials: KJ
authors.lastname: Sidoran
authors.affiliation: Lumiphore, Inc., Berkeley, California, 94710, USA.
authors.forename: D
authors.initials: D
authors.lastname: Magda
authors.affiliation: Department of Health Sciences, Gettysburg College, Gettysburg, PA 17325-1400.
authors.forename: N A
authors.initials: NA
authors.lastname: Mitchell
authors.affiliation: Center for Multidimensional Carbon Materials (CMCM), Institute for Basic Science (IBS), Ulsan 689-798, Republic of Korea; Department of Chemistry and Department of Energy Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Republic of Korea.
authors.forename: C W
authors.initials: CW
authors.lastname: Bielawski
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Lynch
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Sessler
authors.affiliation: Department of Chemistry, Wright State University, 3640 Colonel Glenn Hwy, Dayton, Ohio, 45435, USA.
authors.forename: K
authors.initials: K
authors.lastname: Arumugam