Chemical Education Today edited by
NSF Highlights
Susan H. Hixson
Projects Supported by the NSF Division of Undergraduate Education
National Science Foundation Arlington, VA 22230
Richard F. Jones
An NMR-Smell Module for the First Semester General Chemistry Laboratory
Sinclair Community College Dayton, OH 45402-1460
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by Erich S. Uffelman,* Elizabeth H. Cox, J. Brown Goehring, Tyler S. Lorig, and C. Michele Davis
NMR spectrometers are crucial tools in modern chemistry, and entire undergraduate laboratory curricula are being designed around them (1). Various ways of incorporating NMR spectroscopy into the general chemistry curriculum are being reported (2). Over the past six years, we have developed a series of new NMR experiments across our undergraduate curriculum based on the acquisition of a 400 MHz multinuclear FT-NMR with the assistance of the NSF-ILI program (3). We describe here a module of experiments we have developed in collaboration with our Neuroscience Department. We have run this module in both two-week and three-week formats in our first-term general chemistry course (Chem 111). We have also used portions of this module in our summer program for visiting high school students. The module includes an exploration of organic stereochemistry via hands-on model building, several chemosensory smell tests (4), and hands-on use of 13C NMR, thus serving as a powerful interdisciplinary lab involving chemistry, physics, and neuroscience. The student manuals, spectra, and instructor notes used for this course are available in JCE Online.W Context In Chem 111, the main topics include nuclear chemistry, basic quantum mechanics and chemical bonding, periodic trends, types of chemical reactions, states of matter, a survey of industrial chemistry, and basic solid state chemistry. The first term laboratory consists of: analysis of cigarette smoke by TLC and GC–MS (5); a model-building lab involving fundamental VSEPR shapes and Lewis dot structures; the two week NMR-Smell Module; two weeks of qualitative analysis of unknown anions; use of a diode array UV–vis spectrophotometer and tunable dye laser to explore absorbance (6), fluorescence, and chemiluminescence; a gas law experiment investigating the chemistry of nitrogen oxides (7); a solid state model building lab (8); and an experiment involving solid state LEDs and photocells (9). Thus, the module occurs within a laboratory and classroom context that emphasizes spectroscopy and various aspects of chemical structure. The NMR-Smell Module, as currently run in our labs, consists of one week of model building and a second week of smell and NMR work. The NMR-Smell Module fits into the rest of our curriculum as follows: The second semester of General Chemistry, Chem 112, covers aqueous equilibria (Ksp, Kw, Ka, Kb, pH, etc.) and complexation, basic electrochemistry, thermodynamics, kinetics, and methods of handling data sets using statistical analysis. Our two-term course in Organic Chemistry (Chem 241/ 242) is fairly traditional. Our NMR-Smell Module from Chem 1368
111 assists students in learning stereochemistry in greater detail in first-term Organic, and the module also makes the treatment of NMR spectroscopy in the second term of Organic less frenzied for the students. Students use the NMR spectrometer in the second-term Organic lab. Chemistry majors take a lecture and laboratory course in Organic Spectroscopy (Chem 243) in which they use NMR to solve the structure of increasingly complicated unknown samples. Our B.S. majors take a standard twoterm Physical Chemistry sequence, Advanced Analytical, Biochemistry, and an Inorganic Chemistry course that features a laboratory involving extensive NMR use (including NMR of paramagnetic materials). B.S. majors select further advanced courses from the areas of Organic, Inorganic, and Physical Chemistry. NMR-Smell Module Week 1: Model Building The pre-lab lecture for the first week summarizes and explains stereochemical terms discussed in the lab manual: conformers, constitutional isomers, diastereomers, enantiomers, and stereogenic or chiral centers. The importance of organic stereochemistry to the pharmaceutical industry is also discussed; for example, the classic thalidomide story is briefly recounted (10). During the lab, students working in pairs make models of cyanate and fulmanate, 1-butanol and 2-butanol, Z-2-butene and E-2-butene, glycine, alanine, cysteine, deoxyribose, glucose, and ∆ and Λ complexes of metal ions coordinated by three bidentate ligands. Students model and compare different isomers and conformers of these molecules, deduce the conformational or isomeric relationship present, and identify the number of stereogenic centers in some of the molecules. Students use mirrors to compare the mirror image of a model to its enantiomer. Laboratory instructors circulate around the lab checking students’ models and their conclusions. The lab manual guides the students through the model building process and discusses relevant biological examples where appropriate (e.g., deoxyribose and glucose as structural units in biopolymers, amino acids in biopolymers, etc.). A real benefit of the model building exercise conducted with the instructors’ assistance is that it emphasizes making connections between the 2-D representation of chemical structures on paper and the 3-D molecules those representations depict. To determine the stereochemical relationship between structures and to build accurate models, students not only must notice drawing conventions such as bold and dashed wedges but also must interpret their meaning. The pre-lab lecture and the laboratory combined take about 3.25 hours to complete with a lab section of 20–28 students and two instructors.
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Chemical Education Today
NMR-Smell Module Week 2: Olfaction and NMR During the four hour lab period, students complete the following, in groups: perform a set of smell tests of four compounds; acquire a 13C NMR spectrum of one of the four compounds; answer a set of problems and questions on NMR and MRI; and read an article and answer questions on olfaction. Groups are rotated through the NMR during the lab period. Two pre-lab lectures precede this second week of the module. The first lecture discusses the distinction between a symmetric and asymmetric environment vis-à-vis the behavior of chiral molecules, and it explains the procedures in the lab manual to be employed in the smell tests. Especially, the students are told how to run a crude version of the Connecticut Chemosensory Clinical Research Center Smell Test (11), which doctors use to measure olfactory acuity in patients. Working in pairs, students obtain a stock solution of 1% aqueous 1-butanol and use test tubes and a 10 mL graduated cylinder to generate a dilution series of seven aqueous 1-butanol solutions. Students work with their partners and use the dilution series to test their olfactory acuity in their left and right nostrils using what psychologists term a “two alternative forced choice procedure”. Students report their data on a whiteboard in front of the lab under the headings female left and right nostril, and male left and right nostril. When these experiments are conducted on large numbers of subjects using proper equipment to introduce the odorant from uniform standard solutions to the subject, females on average score higher olfactory acuity than males, and the left nostril of all individuals is, on average, more acute than the right nostril. In several years running this experiment as indicated above, our students never generate results that correlate to those in the literature in a statistically meaningful way, but we actually use that to discuss the difference between wellcontrolled experiments (which the students do most of the semester) and the version of the smell test they have just performed. The students are asked as a group to speak out and identify flaws in the procedure. The students always do a good job with this discussion and identify the following problems: seven consecutive dilutions run with graduated cylinders produce concentrations of 1-butanol that differ among the pairs of students; different students hold the test tubes at different distances from their partners’ nostrils during the tests; some students’ partners are wearing various perfumes or lotions on their hands, which can mask the odor of the test tube solution they are holding near their partner’s nose; some students are inevitably sick or have colds when they are taking the smell test; the number of students in the lab (20–28) does not constitute a large enough group to be statistically meaningful; and so on. After the smell test, students are then asked to identify, or at least distinguish between, some unknown odors. The materials they smell are 1-butanol, 2-butanol, diethyl ether, R-carvone, and S-carvone. With the 1-butanol, 2-butanol, and diethyl ether series, students discover that they can smell the difference between constitutional isomers. With R-carvone and S-carvone, students discover they can smell the difference be-
tween enantiomers. Interestingly, in running this experiment, one author of this paper discovered that he has a difficult time distinguishing the smell of racemic 2-butanol and diethyl ether. Over the past six years, running this experiment on 80– 100 students per year, we discovered that about 10% of all students have a similar inability to easily distinguish between 2-butanol and diethyl ether. This actually makes the lab discussion of olfactory differences in a population, and the discussion of anosmia (the loss of the sense of smell), much more concrete to the students. Following these smell tests, students read an article on olfaction from the popular scientific literature (12) and answer a set of questions about the reading. The reading and questions are not only useful pedagogically for connecting the chemistry and neuroscience, they are also useful logistically, because the pairs of students running their smell tests work at different rates; students who are done with the smell tests can proceed to the reading and questions while their peers catch up. In order to show that physics has direct relevance to fundamental chemical spectroscopy, some of our second lab lecture and lab manual material explains the basic physical phenomenon of magnetism. In the lab lecture and lab manual, very basic magnetic fields are discussed. We demonstrate magnetic field lines using metal filings, compasses, permanent magnets, and coils of wire. The superconducting solenoid coil at the heart of the NMR is described, as well as the cryogens used to cool it. The magnetic field generated by a spinning nuclear charge is discussed, and the energy differences in a magnetic field between the quantized spin states are described. While students perform the smell tests in the lab, groups of 4–6 students are taken to the NMR room. The students take turns at the controls of the computer and load a sample of either 1-butanol, 2-butanol, R-carvone, or S-carvone (dissolved in CDCl3) into the instrument. They then shim the magnet and execute a 13C NMR spectrum of the sample. During this 15 minute process, an instructor describes what the instrument is doing, uses a compass to show the magnetic field lines emanating from the superconducting magnet, describes the superconducting solenoid coil at the heart of the magnet, shows the liquid nitrogen and liquid helium refill ports, compares and contrasts NMR to MRI (13), and explains why many 13C NMR spectra must be signal averaged to obtain the final 13C NMR spectrum. The explanation of the similarities and differences between the NMR and MRI processes (and the questions the students answer on those topics on their worksheets) is one of the most popular parts of the lab, since many of the students have medical school aspirations, and since some of the students have actually had an MRI scan performed on them in a hospital. Using the compass to trace the field lines emanating from the superconducting magnet also grabs students’ attention. Students leave the NMR room with a printout of the spectrum and return to the lab where the smell tests are conducted; the instructor takes the next set of students to the NMR room. The students in the lab work a set of problems and questions pertaining to the NMR process with the help of their lab partners and an instructor. Since the students have
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NSF Highlights smelled the same molecules which they have studied in the NMR spectrometer, they can compare the strengths and weaknesses of their noses and the NMR as analytical instruments. Students conclude that the nose can distinguish between enantiomers and that the NMR cannot do so without a chiral shift reagent (which they examined with models the previous week), and that the nose can detect very tiny quantities of material. Students conclude, obviously, that the nose does not provide structural data that the NMR does provide. In the three-week version of this module, when there is more time to focus exclusively on the NMR experiment, students are shown in greater detail how different compounds are characterized by NMR spectroscopy. In particular, the students see why even though 1-butanol, 2-butanol, and diethyl ether all have four carbons, the diethyl ether only gives two 13C signals.
Surveys of the students taken a year later in organic chemistry indicate that the module is quite successful. Fewer than 10% of students say that the module did not help them in their organic class; over half say that although they did not remember the module at a high level of detail, it made them feel much more comfortable with organic stereochemistry and enabled them to learn the material more thoroughly and more easily in the organic class; and about 10% of the students said that they actually went back to their Chem 111 lab notes to study their organic stereochemistry. Our organic chemistry faculty noticed a jump in students’ performances on the first organic stereochemistry quiz when the first students who had been through the NMR-Smell Module took their courses, and our organic faculty were also able to move more quickly through their discussion of NMR spectroscopy once they had students who had already seen the basics.
High School Summer Version of the Module
Hazards
The Summer Scholars Program at Washington and Lee University gives college-bound high school students the chance to sample college life for four weeks. For prospective science majors, the chemistry department has offered different programs over the years. During one summer, the fourweek program involved basic biochemistry. The NMR-Smell Module was run with the Summer Scholars as follows: (1) lecture about stereochemistry and model building, (2) lecture about olfaction and 3-D chemical structure, (3) lab day with the smell test and isomers, (4) lecture about NMR and MRI, with pictures of scans of normal brains versus those showing tumors, AIDS dementia, and Alzheimer’s disease, (4) lab day involving hands-on experience with 13C NMR spectroscopy. The NMR-Smell Module did an excellent job of catching the attention of the high school students, and they were excited about using “real” equipment.
Students are given a list of possible health hazards associated with strong magnetic fields (for example, pacemakers and metal implants) and told to inform the instructors if they should be kept a safe distance from the NMR magnet. The organic compounds used in the smell tests should not be inhaled in significant quantity (particularly the diethyl ether), and lab ventilation is maintained at maximum air turnover. The 1-butanol used in the Connecticut Chemosensory Clinical Research Center Smell Test is given to the students as an approximately 1% aqueous solution, even before the students further dilute it.
Assessment Our assessment of our students’ learning has taken several forms. Currently, the Chem 111 students take a 20minute quiz the week following the module. The quiz tests their ability to identify stereogenic centers, stereochemical relationships between 2-D drawings of molecules, and their understanding of stereochemical, NMR, and olfaction terminology. The end of term, three-hour cumulative final exam also tests the students on the NMR-Smell Module. Based on several years of running this experiment, we know that what students take from the NMR-Smell Module at the end of Chem 111 is a very basic knowledge of the physics of the NMR process, the ability to identify different types of organic isomerism, the ability to identify stereogenic centers in molecules, and a basic knowledge of the importance of 3-D structure in chemistry. The less quantifiable, but in some ways more important, benefits of the module are that students really appreciate getting to “touch and play” with the NMR, they enjoy running the smell tests and seeing the strengths and limitations of their noses as analytical instruments, and the pre-medical students like seeing how the basic chemistry and physics of NMR relate to MRI. 1370
Acknowledgments We thank the National Science Foundation ILI program (Grant No. DUE-9650033) for support in purchasing our JEOL Eclipse+ 400 MHz spectrometer. ESU thanks the Washington and Lee University Glenn Grant program for summer support and also thanks the Washington and Lee Class of 1965 for two Excellence in Teaching Awards that supported development of new NMR experiments across the chemistry department curriculum. This work is dedicated to Arnold George in recognition of his recent retirement and years of pedagogical service in developing chemical education materials and workshops for grade school teachers. W
Supplemental Material
Instructor notes, detailed procedures for the laboratory, and student handouts are available in this issue of JCE Online. Literature Cited 1. See for instance: (a) Davis, D. S.; Moore, D. E. J. Chem. Educ. 1999, 76, 1617–1618; (b) Vaughn, J. B., Jr. J. Chem. Educ. 2002, 79, 306–307; (c) Ball, D. B.; Miller, R. J. Chem. Educ. 2002, 79, 665–666. 2. See for instance: (a) Dávila, R. M.; Widener, R. K. J. Chem. Educ. 2002, 79, 997–999; (b) Byrd, H.; O’Donnell, S. E. J. Chem. Educ. 2003, 80, 174–176. 3. (a) France, M. B.; Alty, L. T.; Earl, T. M. J. Chem. Educ. 1999,
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5.
6.
7.
76, 659–660; (b) France, M. B.; Uffelman, E. S. J. Chem. Educ. 1999, 76, 661–665; (c) Alty, L. T. Terpene Unknowns Identified Using IR, 1H-NMR, 13C-NMR, DEPT, COSY and HETCOR, submitted to J. Chem. Educ.; (d) Uffelman, E. S.; Doherty, J. R.; Schulze, C.; Burke, A. L.; Bonnema, K.; Watson, T.; Lee, D. W., III. Microscale Syntheses and 1HNMR Spectroscopic Investigations of Square Planar Macrocyclic Tetraamido-N Cu(III) Complexes Relevant to Green Chemistry, J. Chem. Educ., in press; (e) Uffelman, E. S.; Doherty, J. R.; Schulze, C.; Burke, A. L.; Bonnema, K.; Watson, T.; Lee, D. W., III. Microscale Syntheses, Reactions, and 1H-NMR Spectroscopic Investigations of Square Planar Macrocyclic Tetraamido-N Co(III) Complexes Relevant to Green Chemistry, J. Chem. Educ., in press. Part of the inspiration for the component of our experiment dealing with the olfaction of enantiomers was derived from work done at University of California, Berkeley. Kegley, S.; Stacey, A. M. How Do We Detect Odors? PKAL Conference, Hendrix College; Conway, AR, September, 1995. Atterholt, C.; Butcher, D. J.; Bacon, J. R.; Kwochka, W. R.; Woosley, R. J. Chem. Educ. 2000, 77, 1550–1551. The experimental details are available at: http://sparkychem.wcu.edu/ gc-ms/gc-ms-exp.html (accessed Aug 2003). (a) Deng, T.; Acree, W. E., Jr. J. Chem. Educ. 1999, 76, 1555– 1556; (b) Machado, C.; Machado, V. G. J. Chem. Educ. 2001, 78, 649–651. Mattson, Bruce. Microscale Gas Chemistry, 2nd ed.; Educational Innovations: Norwalk, CT, 2001; pp 55–65. See also http://mattson.creighton.edu/Microscale_Gas_Chemistry.html (ac-
cessed Aug 2003). 8. Ellis, A. B.; Geselbracht, M. J.; Johnson, B. J.; Lisensky, G. C.; Robinson, W. R. Teaching General Chemistry: A Materials Science Companion; American Chemical Society: Washington, DC, 1993; pp 97–129. 9. Ellis, A. B.; Geselbracht, M. J.; Johnson, B. J.; Lisensky, G. C.; Robinson, W. R. Teaching General Chemistry: A Materials Science Companion; American Chemical Society: Washington, DC, 1993; pp 401–413. 10. For a brief history of thalidomide, see Botting, J. Drug News & Perspectives 2002, 15, 604–611. 11. See the CCCRC Web site at http://www.uchc.edu/ uconntasteandsmell/clinicalres.html (accessed Aug 2003). 12. Freedman, D. H. In the Realm of the Chemical Discover 1993, June, 69–76. 13. For related NMR-MRI demonstrations, see: Olson, J. A.; Nordell, K. J.; Chesnik, M. A.; Landis, C. R.; Ellis, A. B.; Rzchowski, M. S.; Condren, S. M.; Lisensky, G. C. J. Chem. Educ. 2000, 77, 882–889.
In the NSF Highlights column, recipients of NSF CCLI grants share their project plans and preliminary findings. Erich S. Uffelman, Elizabeth H. Cox, and J. Brown Goehring are in the Department of Chemistry, Washington and Lee University, Lexington, VA 24450;
[email protected]. Tyler S. Lorig is in the Department of Neuroscience, Washington and Lee University, Lexington, VA 24450. C. Michele Davis is in the Department of Chemistry, Georgia Southern University, Statesboro, GA 30460.
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