Chemical Education Today
Reports from Other Journals
Research Advances by Angela G. King
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Figure 1. Dental fluorosis caused by high concentrations of fluoride in drinking water.
photo: AAAS
Teachers often struggle to excite students about geology, with most young people in today’s technology-driven society being unfamiliar with rocks and minerals. Discussions centered on medical geology, the science that studies the link between normal environmental factors and geographical distribution of health problems, may help bridge the gap. Medical geologists work to determine proper exposure levels for humans in regard to essential minerals. Paracelsus (1493–1541) said “All substances are poisons. There is none which is not a poison. The right dosage differentiates a poison and a remedy.” Chandra Dissanayake, a geochemical research pioneer from the University of Peradeniya, agrees with him in an eloquent essay highlighting the emerging field of medical geology. First, Dissanayake asks readers to consider fluoride. In the United States it is added to public water systems in low concentrations to promote dental health. On the other hand, children in tropical regions, such as Sri Lanka, may be exposed to fluoride concentrations in drinking water in excess of 1.5 mg/L. The result is dental fluorosis, a dark brown coloration and mottling of the teeth caused by the conversion of hydroxyapatite to fluorapatite (Figure 1). The fluoride comes from metamorphic rock that contains minerals such as mica, hornblende, and fluorite, all of which contain fluorine. On the other hand, too little of an essential mineral can be harmful. About 30% of the world’s population is at risk of iodine deficiency disorder (IDD), the most common cause of brain damage and mental retardation (Figure 2). As with dental fluorosis, tropical populations are the most at risk, in part due to their distance from the sea and the iodide it contains. Other factors include the bioavailability of iodide in soil. While geological research has clearly indicated the role of environmental conditions in human health for the situations described above, many more questions remain. Humans engaged in geophagy, the deliberate and routine consumption of earthy materials such as clay and minerals, have been observed on all continents. It is most common in pregnant women and in tropical populations. While theories about the benefits of geophagy range from trace mineral supplements to detoxification, scientists have yet to identify the reason for this behavior. High-background radiation areas (HBRAs) are found throughout the world. On some black sand beaches in Brazil the external radiation levels can be up to 5 mrad/h, almost 400 times the normal background level in the U.S. Regions in Iran and India have similarly high levels of natural radiation. Yet surprisingly the local populations in the HBRAs appear to suffer no ill consequences from this exposure to high levels of radiation. Can medical geologists unravel the scientific answers? Possibly, but students should be aware of these intriguing questions and encouraged to pursue the training and education needed to join in investigations.
Figure 2. A woman with an endemic goiter caused by low iodine intake. Reprinted with permission from Science 2005, 309, 883–885. Copyright 2005 AAAS.
More Information 1. Dissanayake, Chandraseekara. Global Voices of Science—Of Stone and Health: Medical Geology in Sri Lanka. Science 2005, 309, 883–885. 2. The International Medical Geology Association Web page has more information at http://www.medicalgeology.org/ (accessed Nov 2005). 3. An essay on the field of medical geology is available at http:// www.iht.com/articles/2005/08/17/opinion/sngeolog y.php (accessed Nov 2005). 4. This Journal has previously reported covered the role of fluoride in dental health. See Rakita, Philip E. Dentifrice Fluoride. J. Chem. Educ. 2004, 81, 677. 5. An undergraduate experiment measuring fluoride levels is available in this Journal. See Rum, Gabrielle; Lee, Wen-Yee; Gardea-Torresdey, Jorge. Applications of a U.S. EPA-Approved Method for Fluoride Determination in an Environmental Chemistry Laboratory: Fluoride Detection in Drinking Water. J. Chem. Educ. 2000, 77, 1604.
Look to Soil for New Leads in Arthritis Treatment There is currently no cure available for rheumatoid arthritis, which affects up to 1% of the population. Scientists from Wyeth Research based a search for a new small-molecule arthritis therapy on molecules that affect the production of tumor necrosis factor (TNF-␣), a protein implicated in inflammation and whose transcription is affected by mitogenactivated protein (MAP) kinase-activated kinase 2 (MAPKAPK-2, or MK-2). A collection of microbial fermentation extracts was screened for MK-2 inhibitory activity. While most active extracts contained the known kinase inhibitors equisetin and staurosporine, scientists could not find a known
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photo: Rohana Chandrajith
Eating Clay?
Chemical Education Today
Reports from Other Journals Modeling the Drug Discovery Process: The Isolation and Biological Testing of Eugenol from Clove Oil. J. Chem. Educ. 2002, 79, 90; Wolkenberg, Scott E.; Su, Andrew I. Combinatorial Synthesis and Discovery of an Antibiotic Compound. An Experiment Suitable for High School and Undergraduate Laboratories. J. Chem. Educ. 2001, 78, 784. 3. An account of the discovery of penicillin can contrast modern techniques with historical drug discovery. See Kauffman, George B. The Discovery of Penicillin: Twentieth Century Wonder Drug. J. Chem. Educ. 1979, 56, 454.
The Fate of Tetracyclines
Figure 3. Phaeochromycins A–E, new compounds identified in the extract of soil bacteria fermentation in the search for new anti-inflammatory drugs. Structures provided by A. King.
inhibitor in an extract of Streptomyces phaeochromogenes LLP108 that displayed the ability to inhibit MK-2. To identify the promising compounds, Wyeth’s research team led by Edmund Graziani extracted 1 L fermentation broths of Streptomyces phaeochromogenes LL-P108, a soil actinomycete or rod-shaped bacterium, with ethyl acetate. The extract was further purified by reversed-phase HPLC to give five pure compounds, phaeochromycins A–E (Figure 3). Highresolution Fourier transform ion cyclotron resonance (FT– ICR) mass-spectrometry identified the molecular formula of each compound and NMR spectroscopy was used to determine the complete structure of each. “Natural products have traditionally been an excellent source of antibiotics and anticancer agents. Moreover, recent technological improvements in compound isolation and structure determination have allowed for much more rapid identifications of promising structures that has in turn led us into new areas like inflammation research” says Graziani. Human recombinant MK-2 was used in an ELISA-based assay to determine the natural products’ ability to inhibit MK2. While phaeochromycins D and E were inactive, A and C were found to be weak inhibitors of the target enzyme. ELISA (enzyme linked immunosorbent assays) is an immunoassay that uses an enzyme tethered to an antigen or antibody as a marker for the detection of a specific protein.
Approximately 70% of the 16 million kg of antimicrobial chemicals used each year in the U.S. consists of antibiotics administered to livestock, not to fight infection but to promote animal growth. Tetracyclines (TCs) are a class of broad-spectrum antibiotics administered to livestock as feed and water additives. Since they are poorly absorbed by the animals due to their ability to bind to di- and trivalent metal ions, the majority of the dosage is excreted by the animal and can accumulate in soil with repeated manure application. This raises two areas of concern: First, the development of antibiotic-resistant bacteria in the environment, and second, the potential impact of the accumulated antibiotics on microorganisms in the soil and water. To determine the best method for addressing both areas, scientists need to determine the fate of TCs once released in the environment. TCs structures not only enable them to bind metal ions but also cause them to exist in predominantly zwitterion forms at normal environmental pH (Figure 4). Previous sorption studies focused on isolated soil types where cation exchange is the dominant mechanism. Now a new study by Stephen Sassman and Linda Lee of Purdue University has broadened the database and developed a model for estimating TC sorption across soils that will make environmental management more informed. The Purdue team studied the sorption of three TCs (tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC)) by soil samples of varied pH, amount, and type of clay, ion exchange capacities, and organic carbon. Soil samples were extracted under optimal conditions and analyzed by HPLC for TCs. Sorption concentrations were determined as the difference between the applied mass of the antibiotic and the mass measured in the aqueous phase after
More Information 1. Graziani, Edmund I.; Ritacco, Frank V.; Bernan, Valerie S.; Telliez, Jean-Baptiste. Phaeochromycins A–E, Anti-inflammatory Polyketides Isolated from the Soil Actinomycete Streptomyces phaeochromogenes LL-P018. J. Nat. Prod. 2005, 68, 1262–1265. 2. Three teaching labs on drug discovery are available in this Journal. See Wentland, Mark P.; Raza, Shaan; Gao, Yingtong. 96-Well Plate Colorimetric Assay for Ki Determination of (±)-2-Benzylsuccinic Acid, an Inhibitor of Carboxypeptidase A: A Laboratory Experiment in Drug Discovery. J. Chem. Educ. 2004, 81, 398; Miles, William H.; Smiley, Patricia M.
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Figure 4. Tetracycline (TC), one of the antibiotics studied for sorption by whole soil samples. Structure provided by A. King.
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Chemical Education Today
Reports from Other Journals
Figure 5. Sorption as a function of soil pH. Image provided by Linda S. Lee.
Figure 6. Comparison to values predicted through modeling. Image provided by Linda S. Lee.
reaching equilibrium. Sorption was measured as a function of time, with 50% of sorption occurring in the first 4 h. For each sample, sorption isotherms were measured for the TC concentration range matching that of swine waste lagoons. The Freundlich sorption model was applied to all sorption data and used to fit isotherms. (More information on the Freundlich model and a reference to the full description of its development can be found at http://www.osti.gov/energy citations/product.biblio.jsp?osti_id=6249149; accessed Dec 2005.) Soil pH was found to be critical in sorption of TCs, with sorption decreasing as pH increases for all but one soil sample (Figures 5 and 6). For soil where cation exchange is the dominant process of sorption, the concentration of the competing inorganic cation is also important. Cation exchange capability (CEC) was clearly shown to contribute to sorption through analysis of trends in sorption isotherm data. Sassman and Lee conclude that in natural soils the three analyzed TCs behave similarly in sorption and transport despite structural variances. They also identify soil pH and CEC as the most important factors in determining the nature of the interaction between the antibiotics and the soil.
More Information
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1. Sassman, Stephen A.; Lee, Linda S. Sorption of Three Tetracyclines by Several Soils: Assessing the Role of pH and Cation Exchange. Environ. Sci. Technol. 2005, 39, 7452–7459. 2. This Journal has previously published an undergraduate lab on sorption by soil. See Xia, Kang; Pierzynski, Gary L. Competitive Sorption between Oxalate and Phosphate in Soil: An Environmental Chemistry Laboratory Using Ion Chromatography. J. Chem. Educ. 2003, 80, 71. 3. Tetracycline has been featured as a “Molecule of the Month” at http://www.chm.bris.ac.uk/motm/tetracycline/tetracycline.htm (accessed Nov 2005). There you will find its chemical and physical properties, and discussion of the bioactivity of the related class of antibiotics. 4. More information on the use of antibiotics in livestock can be found online at http://www.ucsusa.org/food_and_ environment/antibiotic_resistance/index.cfm and http:// www.aphis.usda.gov/vs/ceah/cei/ (both sites accessed Nov 2005).
Angela G. King is Senior Lecturer in Chemistry at Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109;
[email protected].
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