Phone: (864) 656-0481
Office: 481 Hunter Laboratories
Dr. Brumaghim earned her A.B. degree in chemistry from Harvard University in 1994. Her Ph.D. work with Prof. Greg Girolami at the University of Illinois at Urbana-Champaign involved the synthesis of air-sensitive osmium complexes. After graduation in 1999, she was an NIH postdoctoral fellow with Prof. Ken Raymond at the University of California, Berkeley (1999-2001), studying chiral bioinorganic and supramolecular coordination chemistry. She then joined Prof. Stuart Linn's lab in the molecular and cellular biology department at Berkeley to conduct postdoctoral research in the biochemistry of DNA damage and iron interactions with NAD(P)H (2001-2003) before joining the faculty at Clemson University in 2003.
Research in the Brumaghim group aims to understand how metal ions form oxygen radical species that damage DNA and cause cell death, and how antioxidants prevent this damage. Studying DNA damage inhibition by antioxidants may lead to future treatments for cancer and other diseases caused by oxidative damage. Research projects combine areas of coordination chemistry, biochemistry, and toxicology. Because of the diversity of research areas, students will develop skills in both inorganic chemistry and the biochemistry of nucleic acids and oxidative DNA damage.
How do antioxidants prevent DNA damage and cell death?
In cells, Fe2+ and Cu+ react with hydrogen peroxide to form hydroxyl radical, a highly reactive species that damages DNA. This DNA damage is an underlying cause of neurodegenerative and cardiovascular diseases, as well as many cancers. Antioxidants prevent hydroxyl radical from damaging DNA, and are of interest to treat and prevent these diseases.
Selenium and sulfur compounds are well-known antioxidants. In clinical trials, patients given selenium supplements have significantly lowered their cancer risk. The goal of our research is to provide a chemical explanation for clinical observations of selenium and sulfur antioxidant activity. In addition to selenium and sulfur antioxidants, we also examine the antioxidant activity of polyphenol antioxidants found in fruit, vegetables, and teas. Using gel electrophoresis, we recently discovered that all three classes of antioxidants prevent metal-mediated DNA damage through iron or copper coordination. Currently we are testing a variety of antioxidants to determine the chemical features that lead to better DNA damage prevention. Understanding this novel metal-binding mechanism of antioxidant activity will aid the design and identification of more potent antioxidant compounds.
Because we found that antioxidants prevent DNA damage in vitro by metal coordination, we are also testing the ability of antioxidants to protect cells from DNA damage and cell death under conditions of oxidative stress. When cells (both bacterial and mammalian) are exposed to hydrogen peroxide, many die due to the DNA damage from iron-generated hydroxyl radical. Adding antioxidants to the cell culture can prevent this oxidative cell death, and we are examining the cellular mechanisms and structure-activity relationships that lead to improved antioxidant behavior.
What is the role of metal coordination in antioxidant activity?
Since metal coordination by selenium, sulfur, and polyphenol antioxidants is required for antioxidant activity, we are interested in synthesizing selenium, sulfur, and polyphenol complexes of iron and copper. With these complexes, we are studying the effects of antioxidant coordination on Fe(II)/Fe(III) or Cu(I)/Cu(II) redox potentials and reactivity with hydrogen peroxide. Results from these experiments will allow us to determine chemical mechanisms for antioxidant activity based on metal binding.
To synthesize our target selenium and sulfur compounds, we use nitrogen donor ligands such as Tp* and Tpm* (tris(3,5-dimethyl-pyrazolyl)borate and –methane, respectively) ligands to coordinate copper and iron. Our starting complexes have exchangeable solvato ligands such as acetonitrile that can be replaced with selenium, sulfur, and polyphenol ligands. We are currently interested in synthesizing biologically-relevant chelating ligands as well as synthesizing and characterizing our target antioxidant complexes by NMR, X-ray crystallography, and cyclic voltammetry.
Joining the Brumaghim group:
Undergraduate and graduate researchers. To set up an appointment, please send an email with your academic and/or research background as well as the area(s) of research that interest you. Students of all levels and backgrounds are encouraged to apply.
Postdoctoral researchers. Please send an application by regular mail or email with your CV (including academic and research background), a publication list, and the names and contact information of three references. Also indicate the area(s) of research that most interest you. Incomplete applications may not be considered.
Underwood, C. C.; Stadelman, B. S.; Sleeper, M. L.; Brumaghim, J. L. "Synthesis and Electrochemical Characterization of [Ru(NCCH3)6]2+, Tris(acetonitrile) Tris(pyrazolyl)borate, and Tris(acetonitrile) Tris(pyrazolyl)methane Ruthenium(II) Complexes," Inorg. Chim. Acta 2013, 405, 470-476.
Kimani M. M.; Wang H. C.; Brumaghim, J. L. "Investigating the copper coordination, electrochemistry, and Cu(II) reduction kinetics of biologically relevant selone and thione compounds," Dalton Trans. 2012, 41, 5248-5259.
Garcia C. R.; Angele-Martinez C.; Wilkes J. A.; Wang H. C.; Battin E. E; Brumaghim, J. L. "Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism" Dalton Trans., 2012, 41, 6458-6467.
Wang, H. C.; Brumaghim, J. L. "Polyphenol Compounds as Antioxidants for Disease Prevention: Reactive Oxygen Species Scavenging, Enzyme Regulation, and Metal Chelation Mechanisms in E. coli and Human Cells," In Oxidative Stress: Diagnostics, Prevention, and Therapy; Andreescu, S.; Hepel, M., eds.; ACS Symposium Series; American Chemical Society: Washington, DC, 2011, pp. 99-175 (DOI: 10.1021/bk-2011-1083.ch005).
Verdan, A. M.; Garcia, C. R.; Wang, H. C.; Henry, W. P.; Brumaghim, J. L. "Fe(II) Binding of 3-Hydroxychromone, 5-Hydroxychromone, and Sulfonated Morin: Antioxidant Activity of Flavonoids with Competing Metal Binding Sites," J. Inorg. Biochem. 2011, 105, 1314-1322.
Quarles, C. D.; Marcus, R. K.; Brumaghim, J. L. "Competitive Binding of Fe(III), Cr(III), and Ni(II) to Transferrin," J. Biol. Inorg. Chem. 2011, 16, 913-921.
Kimani, M. M.; VanDerveer, D.; Brumaghim, J. L. "The Diselanylbis(1,3-dimethyl-1H-imidazol-3-ium) Dication Stabilized by the Polymeric catena-Pentachloridotricuprate(I) Anion," Acta Crystallogr. 2011, C67, m208-m210.
Grimland, J.; Wu, C.; Ramoutar, R. R.; Brumaghim, J. L.; McNeill, J. "Highly Efficient Singlet Oxygen Generation by Polymer Nanoparticles," Nanoscale 2011, 3, 1451-1455.
Kimani, M. M.; Bayse, C. A.; Brumaghim, J. L. "Synthesis, Characterization, and DFT Studies of Thione and Selone Cu(I) Complexes with Variable Coordination Geometries," Dalton Trans. 2011, 40, 3711-3723.
Perron, N. P.; Garcia, C. R.; Pinzon, J. R.; Chaur, M. N.; Brumaghim, J. L. "Antioxidant and Prooxidant Effects of Polyphenol Compounds on Copper-Mediated DNA Damage," J. Inorg. Biochem. 2011, 105, 735-743.
Battin, E. E.; Zimmerman, M. T.; Ramoutar, R. R.; Quarles, C. E.; Brumaghim, J. L. "Selenium Compounds Prevent Copper- and Iron-Mediated Oxidative DNA Damage," Metallomics 2011, 3, 503-512.
Quarles, C. D.; Brumaghim, J. L; Marcus, R. K. "Instrumental Comparison of the Determination of Cr(III) Uptake by Human Transferrin," Metallomics 2010, 2, 792-799 (cover article).
Perron, N. R.; Wang, H. C.; DeGuire, S. N.; Jenkins, M.; Lawson, M.; Brumaghim, J. L. "Kinetics of Iron Oxidation upon Polyphenol Binding," Dalton Trans. 2010, 41, 9982-9987.
Kimani, M. M.; Brumaghim, J. L.; VanDerveer, D. "Probing the Antioxidant Action of Selenium and Sulfur Using Cu(I)-Chalcogenone Tris(pyrazolyl)methane and -borate Complexes," Inorg Chem. 2010, 49, 9200-9211.
Quarles, C. D., Jr.; Brumaghim, J. L.; Marcus, R. K. "Simultaneous Multiple Element Detection by Particle Beam/Hollow Cathode-Optical Emission Spectroscopy as a Tool for Metallomic Studies: Determinations of Metal Binding with Apo-Transferrin," Metallomics 2010, 2, 154-161.
Battin, E. E.; Brumaghim, J. L. "Antioxidant Activity of Sulfur and Selenium: A Review of Reactive Oxygen Species Scavenging, Glutathione Peroxidase, and Metal Binding Antioxidant Mechanisms," Cell Biochem. Biophys. 2009, 55, 1-23 (invited review).
Battin, E. E.; Lawhon, A.; Hamilton, D. H.; Brumaghim, J. L. "Using Proteins in a Bioinorganic Laboratory Experiment: Iron Loading and Removal from Transferrin," J. Chem. Ed. 2009, 86, 969-972.
Perron, N. R.; Brumaghim, J. L. "A Review of the Iron-Binding Mechanism for Polyphenol Antioxidant Activity," Cell Biochem. Biophys. 2009, 53, 75-100 (invited review).
Battin, E. B.; Brumaghim, J. L. "Metal Specificity in DNA Damage Prevention by Sulfur Antioxidants," J. Inorg. Biochem. 2008, 102, 2036-2042 (winner of Best Paper by a Young Investigator 2008).
Perron, N. R; Hodges, J. N.; Jenkins, M.; Brumaghim, J. L. "Prediciting How Polyphenol Antioxidants Prevent DNA Damage by Binding to Iron," Inorg. Chem. 2008, 47, 6153-6161.
Ramoutar, R. R.; Brumaghim, J. L. "Investigating the Antioxidant Properties of Oxo-Sulfur Compounds on Metal-Mediated DNA Damage," Main Group Chem. 2007, 101, 1028-1035.
Ramoutar, R. R.; Brumaghim, J. L. "Effects of Inorganic Selenium Compounds on Oxidative DNA Damage," J. Inorg. Biochem. 2007, 101, 1028-1035.
Battin, E. E.; Perron, N. R.; Brumaghim, J. L. "The Central Role of Metal Ion Coordination in Selenium Antioxidant Activity," Inorg. Chem. 2006, 45, 499-501.