|
Assistant Professor, Physical Biochemistry
B.S. 1989, Illinois State University
M.S. 1990, Illinois State University
Ph.D. 1997, Indiana University
Postdoctoral: 2001-2003, Camille and Henry Dreyfus Fellow, Illinois State University
Email: sjpeter@ilstu.edu
Phone: (309)438-2118
Office: 327A Science Laboratory Building
My research interests lie in the chemistry of free radicals particularly those that are
important in biological processes. We are currently investigating the reactivity of nitric
oxide (•NO), a free radical, with various semiquinones or quinone anion radicals. Our motivation
for studying these NO-semiquinone systems is two fold. First, this research will further contribute
to an understanding of the nature of free radical chemistry, and how free radicals such as
semiquinones and possibly •NO act as radical scavengers within biological systems. The second
impetus is that nitric oxide-quinone compounds might have potential pharmacological implications,
and one day be used as •NO donors under physiological conditions. Nitroglycerine is one example of
a pharmaceutical •NO donor currently used as a vasodilator in heart patients. Below is a brief
description of some results investigating the chemistry of nitric oxide with para-benzosemiquinone
via electron paramagnetic resonance (EPR) techniques and some future directions with this research.
•NO chemistry with para-benzosemiquinone (C6H4O2•-)
Over the past two decades, the importance of •NO in many biological processes was realized which led
to an explosion of research on this simple molecule. Science (in 1992) named •NO the molecule of the
year, and in 1998 the Nobel Prize in Medicine was awarded to Furchgott, Ignarro and Murad for
discovering the role •NO plays in the cardiovascular system. Nitric oxide is known to have a multitude
of physiological roles in mammalian systems; some of these include neurotransmission, blood pressure
regulation, and protector against microbial pathogens. Quinones and semiquinones, on the other hand,
play a vital role in biological redox and electron-transfer processes that are important in energy
storage within the body. One class of quinones called ubiquinones (or coenzyme Q) mediates electron
transport in mitochondria, and is believed to act as antitumor agents.
The room temperature potassium metal reduction (in hexamethylphoshoramide, HMPA) of para-benzoquinone
(reaction 1) gives rise to a solution that, upon EPR analysis, gives a strong signal from the anion
radical of para-benzoquinone (C6H4O2•-),
 
Figure 1A. The five line pattern exhibited in the EPR spectrum results from the unpaired electron
coupling with the four equivalent ring hydrogens. Upon addition of excess nitric oxide (relative
to C6H4O2•-) to the reaction vessel, we find that no EPR signal is detected. Surprisingly, by
increasing the amount of potassium used in the reduction, after the addition of •NO, we detect a
new EPR signal, Figure 1B. A rough computer simulation (Figure 1C) of the EPR spectrum reveals
that there are (at least) three anion radical species now present in solution. One of these is simply
a small amount of regenerated C6H4O2•-, while the other two species are believed to be a mono and tri-
substituted •NO benzosemiquinone. In both the mono and tri- substituted systems the nitric oxide
appears to be replacing the ring hydrogens. The simulation is not perfect because it is difficult to
extract the exact EPR coupling constants for these species. At this time we believe structures 1 and 2
are the likely products formed from this chemistry, but further studies are needed to support these findings
and explain the mechanism of their formation. We have performed analogous reactions with the anion
radical of 2,6-di-tert-butyl-para-benzoquinone and •NO and have obtained similar results. These
observations have generated some exciting questions about this •NO/semiquinone chemistry. Why
does the addition of •NO quench the anion radicals in solution? What is the mechanism of formation and
the stability of these newly formed •NO substituted benzoquinone species? Is it possible that this
reaction occurs under physiological conditions?
Figure 1. In my research group, we use a variety of analytical techniques such as 1-D and 2-D multinuclear
NMR and electron paramagnetic resonance (EPR) spectroscopic techniques to elucidate the structures
and the mechanism for the formation of these NO-quinone molecules. Nitric oxide enriched in 15N
can be purchased, and this isotope of nitrogen is especially important and useful in unraveling
the structural details of these nitrogen containing compounds of biological interest. In the
near future, we plan to look at this chemistry with more complex ubiquinone systems such as the
coenzyme Q molecules; these will likely undergo an analogous reaction with nitric oxide.
Finally, high level quantum mechanical calculation will be performed on these species to support
our experimental findings.
|
|
SELECTED PUBLICATIONS
"Interannular Communication in the Radical Anions of Bis-cyclooctatetraene Systems"
Peters, S. J.; Reiter, R. C. and Stevenson, C. D. Org. Lett. 2003, 5, 937.
"Single-Electron Entrapment of [8]Annulyne, Biannulenylenes, and an
Annulenoannulene" Peters, S. J.; Turk, M. R.; Kiesewetter, M. K. and Stevenson, C. D. J. Am. Chem. Soc.
2003, 125, 11264.
"The Cyclooctatriene-η2-ynyl Potassium Zwitterionic Radical: Evidence for a Potassium Organometallic"
Peters, S. J.; Turk, M. R.; Kiesewetter, M. K.; Reiter, R. C. and Stevenson, C. D. J. Am. Chem. Soc.
2003, 125, 11212.
Transient [8]Annulenyl Carbanion from the Anion Radical of Bromo-[8]annulene"
Stevenson, C. D.; Kiesewetter, M. K.; and Peters S. J. J. Phys. Chem. A 2004, 108, 2278.
"Polycyclooctatetraeneoxy Alkane Polyanionic Polyradicals” Stevenson, C. D.; Reiter, R. C.;
Szczepura, L. F. and Peters S. J. J. Am. Chem. Soc. 2005, 127, 421.
|
