Off Switch; Nitrite as a

Jul 1, 2004 - Nitrite as a Potential Therapeutic Agent. Nitrite anions have been found ... Call for papers: 2019 Great Lakes Regional Meeting · ACS Sh...
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Chemical Education Today

Reports from Other Journals

Research Advances by Angela G. King

Research Advances is a new feature in JCE that will bring information about innovations in current areas of research to high school and college science faculty. The intent is to provide educators with timely descriptions of recent progress in research that they can integrate into existing courses to update course content and encourage an appreciation for research among students. To contribute a highlight or suggest a recent breakthrough for coverage, please contact the feature editor at [email protected]. Hydrophobicity On/Off Switch Zinc oxide has been used in a wide range of applications because of its properties as a wide band-gap semiconductor, but new research focuses on zinc oxide’s hydrophobicity. A new material that would self-clean when a light was turned on and then off sounds like science fiction, but researchers at the Institute of Chemistry in Bejing, China, have moved one step closer to making this scenario a reality. Lei Jiang and fellow researchers have made a hydrophobic coating from zinc oxide that repels water, which flows off a coated surface if the surface isn’t level. Exposing the coating to UV light causes it to absorb water molecules into the surface. The surface once again gains its water-repellent nature if kept in the dark for one week. The cycle can be repeated several times with no decrease in wettability, an indication of potential long-term use in applications.

Researchers are currently working to decrease the time between exposure to UV light and a return of super-hydrophobicity. If this change could occur quickly, possible uses could include flushing dirt from a surface or controlling the flow of a liquid on a surface.

More Information 1. Feng, X.; Feng, L.; Jin, M.; Zhai, J.; Jiang, L.; Zhu, D. Reversible Super-hydrophobicity to Super-hydrophilicity Transition of Aligned ZnO Nanorod Films. J. Am. Chem. Soc. 2004, 126, 62– 63. 2. The Nanotube Site. http://www.pa.msu.edu/cmp/csc/ nanotube.html (accessed Apr 2004).

Nitrite as a Potential Therapeutic Agent A new study from the National Institutes of Health shows that nitrite ions could have therapeutic use in treating diseases related to blood flow. Nitrite, a common anion found in the body, relaxes blood vessels and improves blood flow upon reduction by deoxyhemoglobin. The study demonstrates that nitrite can be converted into nitric oxide, a compound known to expand blood vessels and regulate circulation. The finding changes the previously held belief that nitrite had no major function and indicates that it could play a role in the treatment of sickle cell anemia and other heart and vascular diseases. “This study is paradigm breaking regarding the role of nitrite in expanding blood vessels. At the very least it holds promise as a new therapeutic agent for sickle cell anemia and other diseases that include pathophysiological blood flow,” said Daniel Kim-Shapiro, associate professor of physics at Wake Forest University. Researchers focused on the reaction of nitrite in blood. Their experiments measured the amount of nitric oxide bound to hemoglobin made when nitrite was added to blood as a function of time. The researchers measured blood pressure and the amount of Image courtesy D. Kim-Shapiro.

Figure 1. The surface structure of the super-hydrophobic zinc oxide nanorods. Reprinted with permission from J. Am. Chem. Soc., 2004, 126, 62–63. Copyright © 2004 American Chemical Society.

The coated surface looks like a carpet sample. Zinc oxide protrudes from the surface in tiny columns called nanorods. The nanorods, each 50–150 nm in diameter, are prepared on a glass wafer in a two-step process. The change in the hydrophobic nature of the coating is attributed to the photosensitive nature of the structure and the rough texture of the surface. Earlier work on carbon nanotubes demonstrated that the hydrophobicity of a rough surface is increased as the surface area, or proportion of air/solvent interface, increases. 934

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Figure 2. A schematic model for the uptake of nitrite and conversion to NO.

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Chemical Education Today

More Information 1. Contributed by J. McConnico, Wake Forest University News Service, [email protected]. 2. Cosby, K.; Partovi, K.; Crawford, J.; Patel, R.; Reiter, S.; Yang, B.; Waclawiw, Zalos G.; Xu, X.; Huang, K.; Shields, H.; Kim-Shapiro, D.; Schechter, A.; Cannon, III, R.; Gladwin, M. Nitrite Reduction to Nitric Oxide by Deoxyhemoglobin Vasodilates the Human Circulation. Nat. Med. 2003, 9, 1498–1505. 3. Images and news clips available at http://www.wfu.edu/ ~shapiro/research/ (accessed Apr 2004). 4. Information on the use and amounts of nitrites as a food preservative can be found at http://www.amif.org/NitriteFAQ.pdf and http://www.amif.org/SOURCESofnitrite.pdf (accessed Apr 2004); a related laboratory experiment can be found at Glover, I. T.; Johnson, F. T. Determination of Nitrite in Meat Samples. J. Chem. Educ. 1973, 50, 426. 5. Related information can be found in Senozan, N. M.; Nasser-Moaddeli, S. Organic Nitrates and Nitrites as Heart Drugs. J. Chem. Educ. 1984, 61, 674.

Figure 3. Littoraria irrorata, the fungus farmer.

the leaf surface, which promotes invasion and growth of fungi. The snails then consume the nutritious fungus that grows on the wounded grass. Controlled laboratory studies demonstrated that the growth of juvenile snails was proportional to the fungal biomass present in their food. Juvenile snails who were fed a diet of uninjured green leaves suffered a 48% mortality rate. As they graze, snails deposit fecal pellets on the plant’s wounds. More research is needed to clarify if these fecal pellets promote fungal growth due to their high nitrogen content, as nitrogen availability limits the growth of marsh fungi, or contain viable fungal spores. While fungal spores are present across the marsh surface, directly depositing them on wounded plant tissue would be analogous to a farmer planting seeds. In the bigger picture, the grazing of Littoraria irrorata can convert a productive salt marsh grassland to a mudflat in less than eight months if unchecked. Over-harvesting the snail’s natural predators, such as blue crabs, may thus be contributing to the massive die-off of southeastern United States salt marshes.

More Information

Mollusks as Farmers Just as human agricultural efforts employ multiple strategies for producing crops, recent research indicates that farming may be actively pursued by snails in marine environments. A groundbreaking study reports that the marine snail Littoraria irrorata farms fungus in the salt marsh marine environment. With this work, B. Silliman of Brown University and his colleagues have demonstrated for the first time that farming symbioses exist outside of insects and has reported the demonstration of facilitation of fungal invasion as an ecological mechanism for top-down control of plant production. The snails abundantly feed in salt marshes along southeastern U.S. coastlines. Historically thought to be detritivores, the snails were recently shown to graze live salt marsh cord grass. The snails do not ingest live tissue but wound www.JCE.DivCHED.org

Photo courtesy B. Silliman

nitric oxide-bound hemoglobin found in volunteers who had been administered sodium nitrite. It is hypothesized that nitrite is taken up by the red blood cell and converted by deoxygenated hemoglobin to either nitric oxide (NO) or another vasodilating species. The vasodilator is exported from the red blood cell to smooth muscle cells resulting in vasodilation. Nitrite ions are now considered a vascular storage pool for NO for several reasons. Nitrite anions are present in substantial concentrations and are relatively stable to reductants present in cells. Nitrite’s reaction rate with heme proteins is 10,000 times slower than nitric oxide. Additionally, NO2- is only converted to NO by deoxyhemoglobin, and the other product of this reaction is met(ferric)hemoglobin, which itself limits scavenging and inactivation of nitric oxide. The understanding developed through this research of nitrite as a storage mechanism for nitric oxide and how it may play a role in normal physiology has led to current studies regarding nitrite as a basis for treatments of several diseases and conditions.



1. Silliman, B.; Newell, S. Fungal Farming in a Snail PNAS 2003, 100, 15643–15648. 2. http://www.brown.edu/Administration/News_Bureau/200304/03-060.html (accessed Apr 2004). 3. Newell, S. Y. Fungi in Marine/Estuarine Waters. In The Encyclopedia of Environmental Microbiology; Bitton, G., Ed.; WileyInterscience: New York, 2002, pp 1394–1400. 4. Silliman, B.; Bertness, M. A Trophic Cascade Regulates Salt Marsh Primary Production. PNAS 2002, 99, 10500–10505.

Clotting Gene In 1943 the Nobel Prize in Physiology or Medicine went to Henrik Dam and Edward Doisy for their work characterizing vitamin K. This vitamin is important because of its role in blood coagulation. More than 60 years later, scientists are

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Reports from Other Journals still working to fully understand the role of vitamin K in blood clotting and related disorders. Coagulation of blood involves many proteins, and if any of these factors are missing the result is hemophilia, an inherited bleeding disorder resulting from the body’s inability to produce proteins that cause blood to clot. About one in 10,000 baby boys are born with the condition, best known for afflicting European royalty. Until the development of genetically engineered clotting factors, hemophiliacs had to rely on pooled clotting factors derived from 2,000 to 5,000 blood donors. Gamma-glutamyl carboxylase is one enzyme employed in vitamin K metabolism and blood clotting that ensures that clotting factors work. The gene for gamma-glutamyl carboxylase was identified and cloned in 1991. Now research groups in North Carolina and Germany have reported the identification and cloning of another important gene, bringing hope to hemophiliacs. Vitamin K epoxide reductase (VKOR) converts vitamin K to a usable form. It is the enzyme targeted by warfarin, a commonly prescribed anticoagulant. Warfarin, also known as coumadin, is the 11th most commonly prescribed drug in the U.S. and works by inhibiting VKOR and thus blocking the conversion of vitamin K to its active form. This reduces clotting and the risk of heart attacks and stroke. Millions of patients in the United States are on long-term warfarin therapy, but because individuals respond differently to warfarin, careful patient monitoring is required. Risks include internal bleeding, bruising, unexplained fever, and stomach pain.

“Identification and characterization of the VKOR gene will shed much light on how warfarin works and will benefit future research on thrombosis and heart disease,” said Tao Li, the first author of one report. “It may tell us why different people respond differently to the drug and allow physicians to learn about the best doses for individual patients by analyzing their genes. Before long, we also should be able to create enough enzyme to analyze its structure and later design more effective anticoagulants with fewer side effects.”

More Information 1. http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v427/n6974/full/427493a_fs.html (accessed Apr 2004) 2. Rost, S.; Fregin, A.; Ivaskevicius, V.; Conzelmann, E.; Hörtnagel, K.; Pelz, H.-J.; Lappegard, K.; Seifried, E.; Scharrer, I.; Tuddenham, E.; Muller, C.; Strom, T.; Öldenburg, J.; Mutations in VKORC1 Cause Warfarin Resistance and Multiple Coagulation Factor Deficiency Type 2. Nature 2004, 427, 537–541. 3. Li, T.; Chang, C.-Y.; Jin, D.-Y.; Lin, P.-J.; Khvorova, A.; Stafford, D. Identification of the Gene for Vitamin K Epoxide Reductase. Nature 2004, 427, 541–544. 4. A teaching laboratory experiment on vitamin K epoxide can be found in Thierry-Palmer, M. Synthesis of Vitamin K Epoxide. J. Chem. Educ. 1984, 61, 179.

Angela G. King is Senior Lecturer in Chemistry at Wake Forest University, P. O. Box 7486, Winston-Salem, NC 27109; [email protected]

Mission Statement: Research Advances The purpose of Research Advances is to bring to the attention of high school and college science faculty innovations in current areas of research. Research Advances will provide timely descriptions of recent progress in research that can be integrated into existing courses to update course content and encourage an appreciation for research among students. The column will consist of brief reports of significant research accomplishments. Selections from press releases, current scientific journals, and submissions by principal investigators will be chosen to convey the full range of research topics that involve chemistry, convey the importance of progress in chemical research and increase student curiosity regarding chemical research. Reports on each research project and its advances will be brief but the column will include references to more complete information. Suggestions will be welcomed.

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