By David F. Salisbury
Published Jan. 16, 2004
international team of chemists has developed a new family of
antioxidants that are up to 100 times more effective than Vitamin
“Vitamin E is nature's antioxidant and people have been trying
to improve upon it for more than 20 years with only marginal success.
We have taken a very big step in the right direction,” says Ned
A. Porter, the Stevenson Chair of Chemistry at Vanderbilt. He supervised
the development, which was published in the
European journal Angewandte
Chemie International Edition . The university
has a patent pending on the new compounds.
are molecules that can counteract the damaging effects of
oxygen in tissues and other materials. So
far, the new antioxidants have been tested “in vitro” – in
the test tube. But studies with biological molecules, such as cholesterol,
suggest that the new compounds have properties that could make
them suitable for dietary supplements. Shortly, Vanderbilt researchers
expect to begin the lengthy process of determining how effective
the new the compounds are in living animals and whether they have
any harmful side effects.
market for antioxidants in North America is estimated to be in
excess of $800 million per year. Even if the compounds do not
prove suitable as dietary supplements or neutraceuticals, they
could still have practical value. Many materials used for commerce
can be damaged by oxygen and so are routinely treated with antioxidants.
These materials include plastics, rubber, fuels and lubricants,
agricultural feed and cosmetics.
that led to the new antioxidants was the idea of Vanderbilt graduate
student Derek Pratt: “The summer before I came
to Vanderbilt, I was at a conference in New Hampshire where several
presentations dealt with antioxidants. It just occurred to me that
this was an approach that hadn't been tried before.”
At the time,
Pratt was an undergraduate at Carlton University in Ottawa and
was working with Keith Ingold at the National Research Council
in Canada . When Pratt explained his idea to Ingold, the prominent
chemist advised him to “keep this one for yourself.”
Pratt brought the idea with him when he came to Vanderbilt to
work with Porter. “When Derek suggested this project, I was
immediately intrigued,” says Porter. “And it has turned out to
be one of the most interesting projects I've ever been involved
whose chemical name is a -tocopherol, is a phenol:
It contains a ring made of six carbon atoms with a hydroxyl group
(OH) attached. Ingold, among others, had tried to make better antioxidants
by attaching a nitrogen atom to the carbon ring. Theoretically,
these molecules should be stronger antioxidants but they proved
to be impractical because they were unstable in air.
In addition to attaching a nitrogen atom to the ring, Pratt's
idea was to substitute a nitrogen atom for one of the carbon atoms
in the ring itself. With both substitutions he predicted that the
resulting molecules, called pyridinols, should be more stable in
by Daniel Dubois
Pratt, upper right, and Ned Porter, lower left.
had to address the question of whether the resulting molecules
would be effective antioxidants. He did so by analyzing the properties
of existing antioxidants to determine what made them effective.
Once he had done this, he performed a theoretical analysis to
determine whether pyridinols should also have these properties.
When his analysis confirmed that they should “the pace
really picked up,” he says.
Pratt with Maikel Wijtmans, another graduate student working
in his lab interested in synthesizing new molecules. “Actually,
once you think of it, it's really a pretty simple substitution,” says
Pratt. Still, it took a year to work out a 12-step process that
produced the most effective member of this new class of compounds
in quantities large enough for testing.
order to assess their effectiveness as antioxidants, the Vanderbilt
chemists sent samples to Luca Valgimigli in Professor. G. F. Pedulli's
lab at the University of Bologna . The Italian laboratory is one
of the few in the world capable of determining antioxidant effectiveness.
Valgimigli determined that the best pyridinols the Vanderbilt chemists
had created are as much as 100 times more effective than vitamin
In December, Pratt received his doctorate and moved to the University
of Illinois at Urbana-Champaign to begin a post doctoral fellowship.
He is continuing to work with Porter's group on the new antioxidants.
we try to force lipid oxidation, we find that the pyridinols
are much more effective inhibitors than vitamin E."
a chemical group that makes pyridinols “greasy” – gives
them a chemical affinity for fatty acids – the chemists have
combined their antioxidants with low density lipoprotein ( LDL
or “bad” cholesterol) and found that they appear to protect LDL
molecules from oxidation. That may be significant because one
popular theory for the cause of coronary artery disease is lipid
“When we try to force lipid oxidation, we find that
the pyridinols are much more effective inhibitors than
vitamin E,” says Porter.
One of the chemists' next projects is to make pyridinols
that look as much like Vitamin E as possible. The researchers
have deliberately designed some pyridinols so that they
can attach different types of chemical groups to the
ring in order to make such modifications.
project is to make pyridinols that are water soluble,
unlike vitamin E.
Water soluble varieties should perform
a role similar to that of vitamin C: trapping and
destroying water-soluble “free radicals.” Free radicals
are electrically charged atoms or molecules produced
by oxidation that are potentially harmful to the body
of Derek Pratt
|Illustrations of the chemical structure of vitamin E, left, and two of the
pyridinols, middle and right. The structural differences between the new
antioxidants is subtle, but important. The molecule on the left has a
six-membered ring attached to the phenolic ring, whereas the one on the
right has a five-membered ring. The molecule on the left is about 20 times
better than vitamin E as an antioxidant while the molecule on the right is
about 90 times better.
the researchers have joined forces with three researchers at
the Vanderbilt University Medical Center – Professor of Medicine
Raymond F. Burk, Professor of Biochemistry Daniel C. Liebler
and Professor of Pharmacology Jason D. Morrow – to collaborate
on testing these new compounds in animals. They have submitted
a proposal for federal funding that is currently under review.
The research was supported by the National Science Foundation,
Vanderbilt University , the National Science and Engineering
Research Council of Canada, the University of Bologna and the
Italian Ministry of Research.
Ned Porter 's Research Group
Derek Pratt's home page