Frederick Villamena, PhD

Associate Professor, College of Medicine, Dept. of Biological Chemistry and Pharmacology


  • 2011 Outstanding Thomasian Chemistry Alumni Awardee. .
  • 2009 Visiting Professor. .
  • 2007 Visiting Professor. .
  • 2001-2003 Ruth L. Kirschtein Institutional National Service Award Post Doctoral Fellowship. .
  • 2002 Young Investigator Award 7th International Spin Trapping Meeting. .
  • 2000-2001 CNRS Post Doctoral Fellow. .
  • 1998-2000 ORISE Post Doctoral Fellow. .

Book Chapters


  • Jay L. Zweier and Frederick A. Villamena. 2003. "Chemistry of Free Radicals in Biological Systems." In Oxidative Stress and Cardiac Failure, Armonk: Futura.

Journal Articles


  • Liu, Y.; Song, Y.; Rockenbauer, A.; Sun, J.; Hemann, C.; Villamena, F. A.; Zweier, J. L., 2011, "Synthesis of trityl radical-conjugated disulfide biradicals for the measurement of thiol concentration.." J. Org. Chem.
  • Shah, Z.; Pineda, C.; Kampfrath, T.; Maiseyeu, A.; Ying, Z.; Racoma, I.; Deiuliis, J.; Xu, X.; Sun, Q.; Moffatt-Bruce, S.; Villamena, F.; Rajagopalan, S., 2011, "Acute DPP-4 inhibition modulates vascular tone through GLP-1 independent pathways.." Vascular Pharmacol.


  • Ying, Z.; Kherada, N.; Farrar, B.; Kampfrath, T.; Chung, Y.; Simonetti, O.; Dejuliis, J.; Desikan, R.; Khan, B.; Villamena, F.; Sun, Q.; Parthasarathy, S.; Rajagopalan, S., 2010, "Lipoic acid effects on established atherosclerosis.." Life Sciences 86, 95 - 102.
  • Liu, Y.; Villamena, F.; Song, Y.; Sun, J.; Rockenbauer, A.; Zweier, J., 2010, "Synthesis of 14N and 15N-labeled trityl-nitroxide biradicals with strong spin-spin interaction and improved sensitivity to redox status and oxygen." Journal of Organic Chemistry 2010, 7796 - 7802.
  • Liu, Y.; Villamena, F. A.; Rockenbauer, A.; Zweier, J. L., 2010, "Trityl-nitroxide biradicals as unique molecular probes for the simultaneous measurement of redox status and oxygenation.." Chem. Commun. 46, 628 - 630.
  • Durand, G.; Poeggeler, B.; Ortial, S.; Polidori, A.; Villamena, F. A.; Boker, B.; Hardeland, R.; Pappolla, M. A.; Pucci, B., 2010, "Amphiphilic Amide Nitrones: A New Class of Protective Agents Acting as Modifiers of Mitochondrial Metabolism." J. Med. Chem. 53, 4849 - 4861.
  • Durand, G.*; Choteau, F.; Prosak, R. A.; Rockenbauer, A.; Villamena, F. A.*; Pucci, B., 2010, "Synthesis, Physical-Chemical and Biological Properties of Amphiphilic Amino Acid Conjugates of Nitroxides." New. J. of Chem. 34, 1909 - 1920.
  • Villamena, F. A.*, 2010, "Superoxide Radical Anion Adduct of 5,5-Dimethyl-1-pyrroline N-Oxide (DMPO). 6. Redox Properties." J. Phys. Chem A. 114, 1153 - 1160.
  • Wang, J.; Dang, V.; Lu, D.; Rivera, B. K.; Villamena, F. A.; Wang, P. G.; Kuppusamy, P., 2010, "Perchlorotrityl Radical-Fluorophore Conjugates as Dual Fluorescence and EPR Probes for Superoxide Radical Anion.." Bioorg. Med. Chem. 18, 922 - 929.
  • Kim, S.-U.; Liu, Y.; Nash, K.; Zweier, J.; Rockenbauer, A.; Villamena, F. A.*, 2010, "Fast Reactivity of Cyclic Nitrone-Calix[4]pyrrole Conjugate with Superoxide Radical Anion: Theoretical and Experimental Studies." The Journal of the American Society 132, 17157 - 17173.


  • Han, Y.; Liu, Y.; Rockenbauer, A.; Zweier, J. L.; Durand, G.; Villamena, F. A.*, 2009, "Lipophilic beta-Cyclodextrin Cyclic-Nitrone Conjugate: Synthesis and Spin Trapping Studies." J. Org. Chem. 74, 5369 - 5380.
  • Villamena, F. A.*, 2009, "Superoxide Radical Anion Adduct of 5,5-Dimethyl-1-pyrroline N-Oxide (DMPO). 5. Thermodynamics and Kinetics of Unimolecular Decomposition." J. Phys. Chem A 113, 6398 - 6403.
  • Liu, Y.; Villamena, F. A.; Sun, J.; Wang ,T. Y.; Zweier, J. L., 2009, "Esterified trityl radicals as intracellular oxygen probes." Free Radic. Biol. Med. 46, 876 - 883.
  • Zuo, L.; Chen, Y. R.; Reyes, L. A.; Lee, H. L.; Chen, C. L.; Villamena, F. A.*; Zweier, J. L.*, 2009, "The Radical Trap 5,5-Dimethyl-1-pyrroline N-oxide Exerts Dose-Dependent Protection Against Myocardial Ischemia-Reperfusion Injury Through Preservation of Mitochondrial Electron Transport.." J. Pharmacol. Exp. Ther. 329, 515 - 523.
  • Durand, G.; Han, Y.; Prosak, R.; Ortial, S.; Rockenbauer, A.; Pucci, B.; Villamena, F. A.*, 2009, "Spin Trapping and Cytoprotective Properties of Fluorinated Amphiphilic Carrier Conjugates of Cyclic versus Linear Nitrones." Chem. Res. Toxicol. 22, 1570 - 1581.


  • Villamena FA,* Liu Y, Zweier JL., 2008, "Superoxide Radical Anion Adduct of 5,5-Dimethyl-1-pyrroline N-Oxide. 4. Conformational Effects on the EPR Hyperfine Splitting Constants.." J Phys Chem A. 112, no. 49, 12607 - 12615.
  • Field SM, Villamena FA.*, 2008, "Theoretical and experimental studies of tyrosyl hydroperoxide formation in the presence of H-bond donors.." Chem Res Toxicol. 21, no. 10, 1923 - 1932.
  • Liu Y, Villamena FA, Zweier JL., 2008, "Highly stable dendritic trityl radicals as oxygen and pH probe.." Chem. Commun. 28, no. 36, 4336 - 4338.
  • Burgett, R. A.; Bao, X.; Villamena, F. A.*, 2008, "Superoxide Radical Anion Adduct of 5,5-Dimethyl-1-pyrroline N-Oxide (DMPO). 3. Effect of Mildly Acidic pH on the Thermodynamics and Kinetics of Adduct Formation." J. Phys. Chem. A 112, no. 11, 2447 - 2455.
  • Liu,Y.; Villamena, F. A.*; Sun, J.; Xu, Y.; Dhimitruka, I.; Zweier, J. L., 2008, "Synthesis and Characterization of Ester-Derivatized Tetrathiatriarylmethyl Radicals as Intracellular Oxygen Probes." J. Org. Chem 73, 1490 - 1497.
  • Durand G, Choteau F, Pucci B, Villamena FA.*, 2008, "Reactivity of Superoxide Radical Anion and Hydroperoxyl Radical with alpha-Phenyl-N-tert-butylnitrone (PBN) Derivatives.." J Phys Chem A 112, no. 48, 12498 - 12509.
  • Kutala, V. K.; Villamena, F. A.; Ilangovan, G.; Maspoch, D.; Roques, N.; Veciana, J.; Rovira, C. and Kuppusamy, P, 2008, "Reactivity of Superoxide Anion Radical with a Perchlorotriphenylmethyl (Trityl) Radical.." J. Phys. Chem. B 112, 158 - 167.
  • Parihar, M. S.; Parihar, A.; Nazarewicz, R. R.; Villamena, F. A.; Vaccaro, P. S.; Ghafourifar, P., 2008, "Inactivation of mitochondrial respiratory chain complex I leads mitochondrial nitric oxide synthase to become pro-oxidative." Biochem. Biophys. Res. Commun. 367, 761 - 767.
  • Han, Y.; Tuccio, B.; Lauricella, R.; Rockenbauer, A.; Zweier, J. L.; Villamena, F. A.*, 2008, "Synthesis and Spin Trapping Properties of a New Spirolactonyl-Nitrone." J. Org. Chem. 73, no. 7, 2533 - 2541.
  • Han Y, Tuccio B, Lauricella R, Villamena FA.*, 2008, "Improved spin trapping properties by beta-cyclodextrin-cyclic nitrone conjugate.." J Org Chem 73, no. 18, 7108 - 7117.


  • Villamena FA*, Merle JK, Hadad CM, Zweier JL, 2007, "Rate Constants of Hydroperoxyl Radical Addition to Cyclic Nitrones: A DFT Study.." J Phys Chem A 111, 9995 - 10001.
  • Dang V, Wang J, Feng S, Buron C, Villamena FA, Wang PG, Kuppusamy P, 2007, "Synthesis and characterization of a perchlorotriphenylmethyl (trityl) triester radical: A potential sensor for superoxide and oxygen in biological systems.." Bioorg Med Chem Lett 17, 4062 - 4065.
  • Dhimitruka I, Velayutham M, Bobko AA, Khramtsov VV, Villamena FA, Hadad CM, Zweier JL, 2007, "Large Scale Synthesis of a Persistent Trityl Radical for Use in Biomedical EPR Applications and Imaging.." Bioorg Med Chem Lett 17, 6801 - 6805.
  • Villamena FA,* Xia S, Merle JK, Lauricella R, Tuccio B, Hadad CM, Zweier JL, 2007, "Role of Intramolecular H-Bond and Electrostatics on the Reactivity of Superoxide Radical Anion with Cyclic Nitrones.." J Am Chem Soc 129, 8177 - 8191.
  • Lu, D.; Villamena, FA*; Zhang, G; Nadas, J; Zweier, JL; Johnson, W; Cardounel, AJ; Wang PG, 2007, "Caged RSNOs: The Next Generation of S-Nitrosothiols.." J Am Chem Soc 129, 5503 - 5514.
  • Villamena FA*, Locigno EJ, Rockenbauer A, Hadad CM, Zweier JL, 2007, "Theoretical and Experimental Studies of the Spin Trapping of Inorganic Radicals by 5,5-Dimethyl-1-Pyrroline N-Oxide (DMPO). 2. Carbonate Radical Anion.." J Phys Chem A 111, 384 - 391.


  • Visinescu, D.; Desplanches, C.; Imaz, I.; Bahers, V.; Pradhan, R.; Villamena, F. A.; Guionneau, P.; Sutter, J.-P, 2006, "Evidence for Increased Exchange Interactions with 5d Compared to 4d Metal Ions. Experimental and Theoretical Insights into the Ferromagnetic Interactions of a Series of Trinuclear [{M(CN)8}3-/NiII] Compounds (M = MoV or WV).." J. Am. Chem. Soc 128, 10202 - 10212.
  • Xia, S.; Villamena, F. A.*; Hadad, C. M.; Kuppusamy, P.; Li, Y.; Zhu, H.; Zweier, J. L, 2006, "Reactivity of Molecular Oxygen with Ethoxycarbonyl Derivatives of Tetrathiatiarylmethyl Radicals.." J. Org. Chem 71, 7268 - 7279.
  • Villamena, F. A.*; Locigno, E. J.; Rockenbauer, A.; Hadad, C. M.; Zweier, J. L, 2006, "Theoretical and Experimental Studies of the Spin Trapping of Inorganic Radicals by 5,5-Dimethyl-1-Pyrroline N-Oxide (DMPO). 1. Carbon Dioxide Radical Anion.." J. Phys. Chem. A 37, 1446 - 1453.
  • Villamena, F. A.*; Locigno, E. J. Rockenbauer, A.; Hadad, C. M.; Zweier, J. L., 2006, "Theoretical and Experimental Studies of the Spin Trapping of Inorganic Radicals by 5,5-Dimethyl-1-Pyrroline N-Oxide (DMPO). 1. Carbon Dioxide Radical Anion.." J. Phys. Chem. A 110, 13253 - 13258.


  • Villamena, F. A.*; Hadad, C. M.; Zweier, J. L, 2005, "Comparative DFT Study of the Spin Trapping of Methyl, Mercapto, Hydroperoxy, Superoxide, and Nitric Oxide Radicals by Various Substituted Cyclic Nitrones.." J. of Phys. Chem. A 109, 1662 - 1674.
  • Velayutham, M.; Villamena, F. A.; Fishbein, J. C.; Zweier, J. L, 2005, "Cancer chemopreventive oltipraz generates superoxide anion radical.." Archives of Biochemistry and Biophysics 435, 83 - 88.
  • Velayutham, M., Villamena, F. A., Navamal, M., Fishbein, J. C., Zweier, J. L, 2005, "Glutathione mediated formation of oxygen free radicals by the major metabolite of oltipraz.." Chem. Res. Toxicol 18, 970–975 -
  • Villamena, F. A.*; Merle, K. J.; Hadad, C. M.; Zweier, J. L, 2005, "Superoxide Radical Adduct of 5,5-Dimethyl-1-pyrroline N-oxide (DMPO). 2. The Thermodynamics of Decay and EPR Spectral Properties.." J. Phys. Chem 109, 6089 - 6098.
  • Locigno, E. J.; Zweier, J. L.; Villamena, F. A.*, 2005, "Nitric Oxide Release from the Unimolecular Decomposition of the Superoxide Radical Anion Adduct of Cyclic Nitrones in Aqueous Medium." Org. Biomol. Chem 3, 3220 - 3227.
  • Villamena, F. A.*; Merle, K. J.; Hadad, C. M.; Zweier, J. L, 2005, "Superoxide Radical Anion Adduct of 5,5-Dimethyl-1-pyrroline N-oxide (DMPO). 1. The Thermodynamics of Formation and Its Acidity.." J. Phys. Chem. A 109, 6083 - 6088.


  • Villamena, F.*; Rockenbauer, A.; Gallucci, J.; Velayutham, M.; Hadad, C. H.;Zweier, J. L, 2004, "Spin Trapping by 5-Carbamoyl-5-methyl-1-pyrroline N-oxide (AMPO): Theoretical and Experimental Studies." J. Org. Chem 69, 7994 - 8004.
  • Villamena, F.*; Hadad, C. ; Zweier, J, 2004, "Theoretical Study of the Spin Trapping of Hydroxyl Radical by Cyclic Nitrones: A Density Functional Theory Approach.." J. Am. Chem. Soc 126, 1816 - 1829.


  • Frederick A. Villamena and Jay L. Zweier, 2003, "Detection of Reactive Oxygen and Nitrogen Species by EPR Spin-Trapping Technique.." Antioxidant and Redox Signaling 6, 619 - 629.
  • Villamena, F.*; Horak, V.; Crist, D, 2003, "Cyclic Voltammetry of Metal Complexes of Nitrones and Nitroxide.." Inorg. Chim. Acta 342, 125 - 130.
  • Villamena, F.*; Hadad, C; Zweier, J, 2003, "Kinetic study and theoretical analysis of hydroxyl radical trapping and spin adduct decay of alkoxycarbonyl- and dialkoxyphosphoryl-nitrones in aqueous media.." J. of Phys. Chem A 107, 4407 - 4414.


  • Methachit, N.; McGrath C.; Stewart, J.; Blans, P.; Villamena, F.; Zweier, J.; Fishbein, J. C, 2002, "Thiolytic Chemistry of Alternative Precursors to the Major Metabolite of the Cancer Chemopreventive Oltipraz.." J. Org. Chem. 67, 9406 - 9413.
  • Villamena, F.; Zweier, J, 2002, "Superoxide Radical Trapping and Spin Adduct Decay of 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BocMPO): Kinetics and Theoretical Analysis.." J. Chem. Soc., Perkin Trans. 2, 1340 - 1344.


  • Villamena, F.* de la Cruz, A, 2001, "Caffeine Selectivity of Divinylbenzene Cross-linked Polymers in Aqueous Media.." J. Appl. Polym. Sci. 82, 195 - 205.


  • Dickman, M.; Ward, J.; Villamena, F.; Crist, D, 1998, "Bis(?-(N-[(methylthio)phenylmethylene] methanamine-N-oxide-O)bis(1,1,1,5,5,5-hexafluoropentane-2,4 -dionato-O,O')nickel(II)).." Acta Crystallogr C54, 929 - 930.
  • Villamena, F.; Dickman, M.; Crist, D., 1998, "Nitrones as Ligands in Complexes of Cu(II), Mn(II), Co(II), Ni(II) and Fe(II) with N-tert-Butyl-ï�¡-(2-pyridyl)nitrone and 2,5,5-Trimethyl-1pyrrroline-N-oxide.." Inorg. Chem. 37, 1446 - 1453.
  • Villamena, F.; Dickman, M.; Crist, D, 1998, "Stabilization of a Nitroxide with ?-Hydrogen by Metals: Structure and Magnetic Properties of Adducts of N-Oxy-N-tert-butyl-(2-pyridyl) phenylmethanamine with Mn(II), Ni(II), and Co(II) Hexafluoroacetylacetonates.." Inorg. Chem. 37, 1454 - 1457.
  • Villamena, F.; Crist, D, 1998, "Metal-Nitrone Complexes: Spin Trapping and Solution Characterization.." J. Chem. Soc., Dalton Trans. 23, 4055 - 4062.