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An
interview with:
Professor Willem Koppenol |
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this interview Professor Willem Koppenol from the Swiss
Federal Institute of Technology (ETH) in Zurich talks with
in-cites about his paper, "Peroxynitrite, a cloaked
oxidant formed by nitric oxide and superoxide," (Chem.
Res. Toxicol. 5 [6]: 834-42, Nov.-Dec. 1992). According to ISI
Essential Science Indicators
Web product, this paper is among the top 15 papers in the
field of Pharmacology & Toxicology, with a total of 593
citations to date. Professor Koppenol’s other work can be
found in the database in both the fields of Biology &
Biochemistry and Pharmacology & Toxicology. Professor
Koppenol has been with ETH Zurich since 1994, where he heads
up the Bioinorganic and Solution Chemistry Group, part of the
Laboratory of Inorganic Chemistry.
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What, in your view, is the significance of this paper for the
field?
In 1990 Joe Beckman1 proposed that in vivo
superoxide could combine with nitrogen monoxide to form peroxynitrite.
He also suggested that peroxynitrous acid could possibly homolyze and
form hydroxyl and nitrogen dioxide radicals. I disagreed with him on
thermodynamic grounds and we therefore decided to combine our results
and try to decide whether peroxynitrite was dangerous by itself, or
underwent homolysis to hydroxyl and nitrogen dioxide radicals, or
heterolysis to the nitryl cation and hydroxide. The conclusion was
that homolysis and heterolysis did not take place; furthermore the
paper summarized the chemistry of peroxynitrite known at that time.
After Hurst and Lymar2 showed in 1995 that the
peroxynitrite anion disappears rapidly via a reaction with carbon
dioxide, the question of homolysis or no homolysis became academic.
Instead, one now would like to know to what extent this carbon dioxide
adduct undergoes homolysis, and yields nitrogen dioxide and
trioxocarbonate(·1-) radicals. As before, we found little evidence
that homolysis is a minor pathway.
(1) Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A., and
Freeman, B.A. (1990) Apparent hydroxyl radical production by
peroxynitrite: Implications for endothelial injury from nitric oxide
and superoxide. Proc. Natl. Acad. Sci. USA, 87, 1620-1624.
(2) Lymar, S.V. and Hurst, J.K. (1995) Rapid reaction between
peroxonitrite ion and carbon dioxide: Implications for biological
activity. J. Am. Chem. Soc., 117, 8867-8868.
How did you decide where to submit or publish your paper?
Chemical Research in Toxicology seemed a natural choice:
Peroxynitrite is a toxin and we presented its chemistry.
If you performed your research again, or published your paper
again, what, if anything, would you do differently and why?
A large part of the paper is dedicated to thermochemical estimates,
necessary to determine which reaction pathway is used by peroxynitrous
acid. Given new insights, I would get only slightly different numbers.
What would you like to convey to the general public about
your work?
Our macrophages, which attack invading bacteria, produce both
nitrogen monoxide and superoxide, which leads to peroxynitrite, as
discussed above. The peroxynitrite oxidizes and nitrates not only
parts of the bacteria, but also healthy tissue. This led Dr. Patricia
Bounds, my wife, to remark that in addition to the known certainties
in life, taxes and death, there is nitration before death.
What are the implications of your work for the future of your
field or neighboring fields?
I already mentioned macrophages. We live in an atmosphere that
contains 21% dioxygen, which is necessary and, at the same time,
toxic. We are trying to find out how reactive simple inorganic
compounds are that are made from nitrogen, oxygen, and carbon. The
implications are related to medicine and health in general.
Willem H. Koppenol Ph.D .
ETH
Zurich
Switzerland
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