SCIENCE & TECHNOLOGY
NWWHNWWHWlIti More than 7,000 papers were presented at the American Chemical hosts. With this "surrogate Society national meeting in Philadelphia last month. Here's a samhead," Lee and Clark have raised pling ofsome ofthe research results discussed there. populations of permethrin-resistant head lice for study
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 p 6 H13 being studied by graduate student Anand Sundararaman, assistant chemistry professor FriederJâkle, and coworkers at Rutgers University, Newark, Ν 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 an other 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 ma terials as chemical sensors. Exposure of a borylated 3-hexylthiophene polymer to a Lewis base such as pyridine (shown), for ex ample, quenches the material's luminescence.
John M. Clark of the Universi ty of Massachusetts, Amherst, have advanced the under standing of the resistance mechanism. Previously, they had found that lice resistance to As many as 12 million peo permethrin arises from a set of ple worldwide are infested with three mutations in the α-sublice each year. Many combat the unit of the voltage-sensitive infestation with products con sodium channel of lice. Now, they have come up with a taining permethrin (shown). ti S^ DNA-diagnosticprotoHowever, head lice have col to detect these re sistance-causing muta tions. This tool could help establish the occurrence of re sistance and allow alternative become resistant to this active control strategies to be used to ingredient. Understanding the prevent resistance from ad basis of this resistance could vancing. Key to developing the help extend the effectiveness protocol is an automated artifi of permethrin and other lice cial membrane/blood feeding insecticides. Toxicologists Si system that Clark has fashioned. Hyeock Lee of Seoul National It allows human head lice to be University, in South Korea, and raised without human or animal
Getting at the root of lice resistance
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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 Chris topher S. Coughlin and techni cian Robert F. Boswell are try ing 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 currendy use several layers of heavy rubber forprotection.Theresearchers work with various grades of Surlyn, DuPont's ethylenemethacrylic 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 mech anism, Coughlin and Boswell hope that they can either mod ify the material or make other polymers that are both selfhealing and fuel resistant. Coughlin says the key to Surlyn's healing powers seems to lie in the polymer's rheology, melt strength, and elasticity Aspeeding bullet heats the material just enough to make the polymer snap back into place.
Oxidized guanine linked to Huntington's Like a dozen other neurode generative disorders, Hunting ton's disease results from the expansion of a string of repeat ed DNA trinucleotides in a dis ease-linked gene. The mecha nism of expansion, however,
remains unknown. Cynthia T. McMurray of the Mayo Clinic College of Medicine, Roches ter, Minn., has data suggesting that oxidation of a guanine in the repeat region to 8-oxoguanine is the first step. Once 8oxoguanine is formed, a cellular glycosylase en2yme is recruited to excise the damaged base, leaving a break in the DNA strand. This break would nor mally be sewn up by another enzyme. Instead, according to McMurray, the unusual trinu cleotide repeat region tends to fold up on itself, forming a mispaired hairpinlike structure. And the repair enzyme nor mally recruited to deal with mispaired bases actually gets trapped on this hairpin. En trapment of the repair enzyme allows the structure to persist long enough for a DNA poly merase tofillin the gap between the original 8-oxoguanine-induced break and the terminal end of the hairpin, thereby ex panding the string of repeated trinucleotides. In mice with Huntington's disease, loss ofthe enzyme that excises 8-oxoguanine prevents trinucleotide ex pansion, she adds.
Did meteorites supply life's phosphorus? The phosphorus that's es sential to biomolecules such as ATP and RNAon 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 phospho rus is abundant in meteorites, in a form known as schreibersite, which is rare on Earth. Pasek and UA assistant plane tary sciences professor Dante S. Lauretta found that, by mere ly mixing it with room-tem-
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MIIMMHIIHHI perature water, schreibersite could form P 2 0 7 , a biochemi cally useful form ofphosphate. Scientists previously found that schreibersite forms Ρ2θ 7 , but those experiments were per formed under extreme condi tions, such as high temperatures.
pesticides, insecticides, and chemical warfare agents are organophosphates. Their bio logical activity is due primarily to their inhibition of the en-
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Researchers at DuPont are
developing insect repellents based on derivatives of nepetalactone, a natural product from catmint (Nepeta catarid). Ac cording 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 deriv atives of reduced nepetalac tone are better than nepeta lactone itself and at least equal the potency of DEET(N,N-diethyl-3-methylbenzamide), the most widely used active ingre dient in commercial products. For example, at 1% wt per vol, a 1:1 diastereomeric mixture of 3-methyldihydronepetalactone (shown) repels mosquitos better than DEETThe compounds are part of DuPont's increasing empha sis on products derivedfromre newable sources, "vvfork contin ues at the company to develop formulations to deliver the ac tive compounds.
Detection of organic phosphates Ionic liquids offer an envi ronmentally friendlier method for detecting organophosphates, according to Chengdong Zhang and Sanjay V Malhotra of New Jersey Institute of Technology Newark. Many 30
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zyme acetylcholinesterase. A well-established assay to detect organophosphates is based on the conversion of acetylthiocholine to thiocholine and ac etate by acetylcholinesterase. In the presence of dithiobisnitrobenzoate, thiocholine forms ayellow product. If the sample contains an organophosphate, no yellow product is formed. The assay is usually carried out in organic solvents, the best be ing cyclohexane. Using the pes ticide paraoxon (shown) as the test compound, Zhang and Malhotra have shown that the assay can be done in ionic liq uids, which are generally less toxic and pose a small er 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 polymor phism comes up, the first thought is of single-base dif ferences in DNA. Only 1% of these so-called SNPs, or singlenucleotide polymorphisms, re sult in a changed amino acid in a protein, however. Purdue University chemistry professor Fred E. Régnier 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 ofthe measles virus into cells. Measles causes about a million deaths annual-
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ly 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 Univer-
sity, inTurkey—have identified a lead compound and a secondgeneration analog that prevent fusion ofthe virus with host cell membranes, a key step in getting inside host cells. The inhibitory potency of the secondgeneration 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 illfamed 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 ofVlrginia, 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. HTTP://WWW.CEN-ONLINE.ORG
