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More than 7,000 papers were presented at the American Chemical
Society national meeting in Philadelphia last month. Here's a
sampling of some of the research results discussed there.
Multiborylated thiophenes as chemical
sensors
 Conjugated
organic polymers are finding a variety of applications as thin-film
materials in electroluminescent and electrochromic devices. Polythiophenes
in particular are popular because they are stable in their neutral
and oxidized forms, and the polymer chain or side groups are easily
modified to fine-tune the physical properties. One type of modification
being studied by graduate student Anand Sundararaman, assistant
chemistry professor Frieder
J”kle, and coworkers at Rutgers University, Newark, N.J.,
is the incorporation of Lewis acid boron centers into thiophene
polymer chains or as terminal substituents of thiophene oligomers.
The researchers find that if the boron atoms are substituted with
electron-withdrawing pentafluorophenyl groups, blue-green luminescence
is observed. In another example, ferrocenyl substituents yield
a dark red polymer. Adducts can be formed between the boron Lewis
acid and Lewis bases, quenching the luminescence or bringing about
a color change, a property that opens up the possibility of using
the materials as chemical sensors. Exposure of a borylated 3-hexylthiophene
polymer to a Lewis base such as pyridine (shown), for example,
quenches the material's luminescence.
Getting at the root of lice resistance
 As
many as 12 million people worldwide are infested with lice each
year. Many combat the infestation with products containing permethrin
(shown). However, head lice have become resistant to this active
ingredient. Understanding the basis of this resistance could help
extend the effectiveness of permethrin and other lice insecticides.
Toxicologists Si Hyeock Lee of Seoul
National University, in South Korea, and John
M. Clark of the University of Massachusetts, Amherst, have
advanced the understanding of the resistance mechanism. Previously,
they had found that lice resistance to permethrin arises from
a set of three mutations in the  -subunit
of the voltage-sensitive sodium channel of lice. Now, they have
come up with a DNA-diagnostic protocol to detect these resistance-causing
mutations. This tool could help establish the occurrence of resistance
and allow alternative control strategies to be used to prevent
resistance from advancing. Key to developing the protocol is an
automated artificial membrane/blood feeding system that Clark
has fashioned. It allows human head lice to be raised without
human or animal hosts. With this "surrogate head," Lee and Clark
have raised populations of permethrin-resistant head lice for
study.
Self-healing fuel tank
Flying the unfriendly skies could become a little safer for
U.S. military pilots, thanks to scientists at Naval
Air Systems Command in Patuxent River, Md. Materials engineer
Christopher S. Coughlin and technician Robert F. Boswell are trying
to develop a self-healing polymer that would quickly close around
bullet holes. The material is highly coveted for fuel tanks in
military planes and helicopters, which currently use several layers
of heavy rubber for protection. The researchers work with various
grades of Surlyn, DuPont's ethylene-methacrylic acid copolymer
that strengthens golf balls and hockey helmets. When shot at,
Surlyn seals over holes, but it degrades around jet fuel. By studying
Surlyn's healing mechanism, Coughlin and Boswell hope that they
can either modify the material or make other polymers that are
both self-healing and fuel resistant. Coughlin says the key to
Surlyn's healing powers seems to lie in the polymer's rheology,
melt strength, and elasticity. A speeding bullet heats the material
just enough to make the polymer snap back into place.
Oxidized guanine linked to Huntington's
Like a dozen other neurodegenerative disorders, Huntington's
disease results from the expansion of a string of repeated DNA
trinucleotides in a disease-linked gene. The mechanism of expansion,
however, remains unknown. Cynthia
T. McMurray of the Mayo Clinic College of Medicine, Rochester,
Minn., has data suggesting that oxidation of a guanine in the
repeat region to 8-oxoguanine is the first step. Once 8-oxoguanine
is formed, a cellular glycosylase enzyme is recruited to excise
the damaged base, leaving a break in the DNA strand. This break
would normally be sewn up by another enzyme. Instead, according
to McMurray, the unusual trinucleotide repeat region tends to
fold up on itself, forming a mispaired hairpinlike structure.
And the repair enzyme normally recruited to deal with mispaired
bases actually gets trapped on this hairpin. Entrapment of the
repair enzyme allows the structure to persist long enough for
a DNA polymerase to fill in the gap between the original 8-oxoguanine-induced
break and the terminal end of the hairpin, thereby expanding the
string of repeated trinucleotides. In mice with Huntington's disease,
loss of the enzyme that excises 8-oxoguanine prevents trinucleotide
expansion, she adds.
Did meteorites supply life's phosphorus?
The phosphorus that's essential to biomolecules such as ATP
and RNA on Earth may have come from meteorites, according to University
of Arizona graduate student Matthew A. Pasek. The source of
this element in biology has been a long-standing mystery. It's
been known that phosphorus is abundant in meteorites, in a form
known as schreibersite, which is rare on Earth. Pasek and UA assistant
planetary sciences professor Dante S. Lauretta found that, by
merely mixing it with room-temperature water, schreibersite could
form P2O7, a biochemically useful form of
phosphate. Scientists previously found that schreibersite forms
P2O7, but those experiments were performed
under extreme conditions, such as high temperatures.
Buzz off
 Researchers
at DuPont are developing
insect repellents based on derivatives of nepetalactone, a natural
product from catmint (Nepeta cataria). According to chemist
Mark A. Scialdone, the insect-repellent activity of nepetalactone
has been known since the 1960s. He and colleagues now find that
some 3-substituted derivatives of reduced nepetalactone are better
than nepetalactone itself and at least equal the potency of DEET
(N,N-diethyl-3-methylbenzamide), the most widely used active ingredient
in commercial products. For example, at 1% wt per vol, a 1:1 diastereomeric
mixture of 3-methyldihydronepetalactone (shown) repels mosquitos
better than DEET. The compounds are part of DuPont's increasing
emphasis on products derived from renewable sources. Work continues
at the company to develop formulations to deliver the active compounds.
Detection of organic phosphates
 Ionic
liquids offer an environmentally friendlier method for detecting
organophosphates, according to Chengdong Zhang and Sanjay V. Malhotra
of New Jersey Institute of Technology,
Newark. Many pesticides, insecticides, and chemical warfare
agents are organophosphates. Their biological activity is due
primarily to their inhibition of the enzyme acetylcholinesterase.
A well-established assay to detect organophosphates is based on
the conversion of acetylthiocholine to thiocholine and acetate
by acetylcholinesterase. In the presence of dithiobisnitrobenzoate,
thiocholine forms a yellow product. If the sample contains an
organophosphate, no yellow product is formed. The assay is usually
carried out in organic solvents, the best being cyclohexane. Using
the pesticide paraoxon (shown) as the test compound, Zhang and
Malhotra have shown that the assay can be done in ionic liquids,
which are generally less toxic and pose a smaller environmental
burden than organic solvents. In fact, the assay works even better
with ethylpyridinium hexafluorophosphate than with cyclohexane.
Finding amino acid polymorphisms
When the word polymorphism comes up, the first thought is of
single-base differences in DNA. Only 1% of these so-called SNPs,
or single-nucleotide polymorphisms, result in a changed amino
acid in a protein, however. Purdue University chemistry professor
Fred E. Regnier
has devised a method called TACT (tagging amino and carboxy terminus)
to detect and identify these rare differences in proteins, called
single amino acid polymorphisms (SAAPs). Identifying such polymorphisms
could eventually be useful in determining which patients are likely
to respond optimally to specific pharmaceutical products. In the
method, control and experimental protein samples separately are
digested into peptides, and each peptide is differently labeled
at the carboxy and amino termini. The labeled peptides are mixed
and then analyzed by mass spectrometry. In the mass spectrum,
peptides found in both control and experimental samples appear
as a doublet of clusters separated by an easily predicted mass
difference. Unpaired clusters are the result of amino acid differences
between the samples and therefore pinpoint SAAPs.
For the relief of measles
 Researchers
have developed nonpeptidic small molecules that inhibit entry
of the measles virus into cells. Measles causes about a million
deaths annually worldwide. An effective vaccine is available,
but it does not always work with young infants, and other people
may refuse it or may not have access to it. For the unimmunized
who develop the disease, a therapeutic could bring relief, but
no effective antimeasles agents are currently available. Now,
postdocs Aiming Sun and Richard K. Plemper of Emory
University and the collaborative team to which they belong--a
group of virologists, synthetic chemists, and molecular modelers
at Emory and at Ankara
University, in Turkey--have identified a lead compound and
a second-generation analog that prevent fusion of the virus with
host cell membranes, a key step in getting inside host cells.
The inhibitory potency of the second-generation agent (shown)
is 260 nM. The team is currently looking for compounds with antimeasles
activity in the low nanomolar range, as well as analogs that will
inhibit membrane fusion by other viruses in the measles family.
Variants of ill-famed drug may find
use in cancer war
Analogs of thalidomide, the drug that gained infamy for causing
birth defects, could be weapons in the war against cancer. According
to Milton
L. Brown, an associate professor of chemistry at the University
of Virginia, thalidomide analogs have strong antiangiogenic effects--that
is, they inhibit the growth of new blood vessels. Antiangiogenic
compounds are gaining importance as cancer chemotherapeutic agents.
They halt the spread of cancer cells by starving them of a blood
supply. Thalidomide itself is being used as an anticancer agent
because its metabolite has such a biological activity. Brown has
been designing and synthesizing analogs that have greater antiangiogenic
effect than that of thalidomide. Some of the compounds he has
prepared not only stop the growth of new blood vessels but also
inhibit the growth of specific cancer cells themselves, such as
those causing prostate cancer, colon cancer, and certain leukemias.
Very few drugs with such dual action are available so far.
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