Our primary interest is in the structure and reactivity of free radicals and radical ions. These paramagnetic species are generated by solid state gamma-irradiation techniques and studied by electron spin resonance (ESR) spectroscopy. The ESR hyperfine pattern of the signal carrier contains detailed information about the spin distribution and geometry that allows the complete molecular structure of the radical to be determined. The ESR technique is also used to follow the unimolecular and bimolecular reactions of these species.
Current work is centered on the important role of vibronic coupling that, in the case of low-lying excited states, brings about an admixture of excited-state character into the wavefunction of the open-shell molecule. This pseudo-Jahn-Teller effect can induce structural distortions resulting, for example, in the twisting of the bicyclo[2.2.2]oct-2-ene radical cation about the olefin bond [Chem. Eur. J. 8, 1074 (2002)]. It also serves to promote radical cation rearrangements, many of these involving either the ring opening of strained molecules or hydrogen-atom transfer.
Recently, we have become interested in the role of radical cation chemistry in biological amine oxidation processes catalyzed by enzymes such as the monoamine oxidases and cytochrome P-450. Some of the drugs that are used to treat Parkinson's disease are inhibitors of these enzymes, and their "suicide" action on the enzyme can be understood in terms of radical cation rearrangements that we can explore directly by ESR spectroscopy. Essentially, it has been proposed that the key step leading to enzyme inactivation by these substrates on oxidation is the conversion of the initially-formed aminium radical cation (a nitrogen-centered radical) of the drug substrate to a carbon-centered radical that subsequently attacks the active site of the enzyme. This kind of rearrangement leads to distonic radical cation formation in which the spin of the unpaired electron (on carbon) and positive charge (on nitrogen) become separated.
We have in fact observed this radical cation rearrangement for the parent cyclopropylamine [J. Am. Chem. Soc. 109, 595 (1987)] and parent allylamine [J. Chem. Soc., Chem. Comm. 1988, 1069] molecules. Remarkably, many of the drugs (tranylcypromine, selegiline, vigabatrin) that are used in the treatment of depression, Parkinson's disease, and epilepsy through the regulation of amine oxidation in the brain contain a cyclopropyl, allyl, or propargyl group adjacent to the amine function. Accordingly, these drug molecules are ideally structured to undergo a similar type of radical cation rearrangement, and our goal is to characterize and study the kinetics of the intermediates that take part in this important process of suicide enzyme inactivation.
Dr. Williams received his B.Sc. degree from University College London in 1949, and an external Ph.D. degree from the University of London in 1960. He was employed at the Atomic Energy Research Establishment, Harwell, United Kingdom from 1949 to 1961 except for a leave of absence as a research and teaching associate at Northwestern University from 1957 to 1959. In 1961 he joined the chemistry faculty at the University of Tennessee.
Dr. Williams was a National Science Foundation Visiting Scientist to Kyoto University, Japan from 1965 to 1966 and was the recipient of a Guggenheim Fellowship in 1972. He has been Chairman of the Gordon Research Conferences on Radiation Chemistry (1971) and Radical Ions (1984), and served as an associate and consultant editor of Radiation Research, the official journal of the Radiation Research Society, from 1994 to 1999.
B.S., University College London (1949)
Ph.D., University of London (1960)
Awards and Recognitions
Alumni Distinguished Service Professor
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L. Blancafort and F. Williams, "Role of Hyperconjugation in the 1,2-Shift Reactivity of Bicyclo[2.1.0]pentane and Cyclopropane Radical Cations: A Computational Study", J. Phys. Chem. A 2012, 116, 10607-10614. Published on the Web, October 8, 2012.
B. Müller, T. Bally, R. Pappas and F. Williams, “Spectroscopic and Computational Studies on the Rearrangement of Ionized [1.1.1]Propellane and Some of its Valence Isomers: The Key Role of Vibronic Coupling,” J. Am. Chem. Soc. 2010, 132, 14649-14660. Published on the Web, September 29, 2010.
F. Williams, G.-F. Chen, S. M. Mattar, P. H. Scudder, D. A. Trieber II, J. G. Saven, D. C. Whritenour, P. Cimino, and V. Barone, “Magneto-Structural Relationships for Radical Cation and Neutral Pyridinophane Structures with Intrabridgehead Nitrogen Atoms. An Integrated Experimental and Quantum Mechanical Study,” J. Phys. Chem. B 2009, 113, 9026-9034. Published on the Web, June 9, 2009.
F. Williams, Review of Electron Paramagnetic Resonance: Elementary Theory and Practical Applications, Second Edition, by John A. Weil and James R. Bolton, Wiley Interscience, John Wiley & Sons, Inc.: Hoboken, New Jersey, 2007, in J. Chem. Ed. 2009, 86, (1) 33-36.
M. Shiotani, A. Lund, S. Lunell, and F. Williams, "Structures of the Hexafluorocyclopropane, Octafluorocyclobutane, and Decafluorocyclopentane Radical Anions Probed by Experimental and Computational Studies of Anisotropic ESR Spectra," J. Phys. Chem. A 2007, 111, 321-338. Published on Web 12/22/2006.
W. Knolle, I. Janovsk, S. Naumov, and F. Williams, "EPR Studies of Amine Radical Cations, Part II: "Thermal and Photoinduced Rearrangements of Propargyl and Allylamine Radical Cations in Low-Temperature Matrices," J. Phys. Chem. A 2006, 110, 13816-13826. Published on Web 12/07/2006.
M. Shiotani, P. Persson, S. Lunell, A. Lund, and F. Williams, "Structures of Tetrafluorocyclopropene, Hexafluorocyclobutene, Octafluorocyclopentene, and Related Perfluoroalkene Radical Anions Revealed by Electron Spin Resonance Spectroscopic and Computational Studies," J. Phys. Chem. A 2006, 110, 6307-6323. Published on Web 04/27/2006.
A. M. ElSohly, G. S. Tschumper, R. A. Crocombe, J. T. Wang, and F. Williams, "Computational and ESR Studies of Electron Attachment to Decafluorocyclopentane, Octafluorocyclobutane, and Hexafluorocyclopropane: Electron Affinities of the Molecules and the Structures of their Stable Negative Ions as Determined from the 13C and 19F Hyperfine Coupling Constants," J. Am. Chem. Soc. 2005, 127, 10573-10583. Published on Web 07/08/05.
F. Williams, "Reevaluation of the Propagation Rate Constant in the Radiation-Induced Cationic Polymerization of Isobutylene in Solution," Macromolecules 2005, 38, 206-209. Published on Web 12/08/04.
I. Janovsk, W. Knolle, S. Naumov, and F. Williams, "EPR Studies of Amine Radical Cations, Part I: Thermal and Photoinduced Rearrangements of n-Alkylamine Radical Cations to their Distonic Forms in Low-Temperature Freon Matrices," Chem. Eur. J. 2004, 10, 5524-5534. Published on Web 09/29/04.
F. Williams, "Nanotech numbers," Chem. & Eng. News 2004, 82, Issue 9, March 1, 2004, p 5.
F. Williams, "Vibronic Coupling in Ionized Organic Molecules: Structural Distortions and Chemical Reactions," Radiat. Phys. Chem. 2003, 67. 211-218. Published on Web 03/19/03.
I. A. Shkrob, K. Takeda, and F. Williams, "Electron Localization in Solid Acetonitrile," J. Phys. Chem. A 2002, 106, 9132-9144.
S. F. Nelsen, L. A. Reinhardt, H. Q. Tran, G.-F. Chen, R. S. Pappas, and F. Williams, "Ionized Bicyclo[2.2.2]oct-2-ene: A Twisted Olefinic Radical Cation Showing Vibronic Coupling," Chem. Eur. J. 2002, 8, 1074-1081.
A. Marcinek, J. Rogowski, J. Gebicki, G.-F. Chen, and F. Williams, "Isomerization of Cubane Radical Cation," J. Phys. Chem. A 2000, 104, 5265-5268.
T. Bally, S. Bernhard, S. Matzinger, L. Truttmann, Z. Zhu, J.-L. Roulin, A. Marcinek, J. Gebicki, F. Williams, G.-F. Chen, H. D. Roth, and T. Herbertz, "The Radical Cation of anti-Tricyclooctadiene and Its Rearrangement Products," Chem. Eur. J. 2000, 6, 849-857.
T. Bally, S. Bernhard, S. Matzinger, J.-L. Roulin, G. N. Sastry, L. Truttmann, Z. Zhu, A. Marcinek, J. Adamus, R. Kaminski, J. Gebicki, F. Williams, G.-F. Chen, and M. Folscher, "The Radical Cation of syn-Tricyclooctadiene and Its Rearrangement Products," Chem. Eur. J. 2000, 6, 858-868.