Enhancing Undergraduate Pedagogy with NMR across the Curriculum

Chapter 2

Enhancing Undergraduate Pedagogy with NMR across the Curriculum

Downloaded by INDIANA UNIV BLOOMINGTON on May 9, 2015 | http://pubs.acs.org Publication Date: August 16, 2007 | doi: 10.1021/bk-2007-0969.ch002

Matthew A. Fisher and Daryle H. Fish Department of Chemistry, Saint Vincent College, 300 Fraser Purchase Road, Latrobe, PA 15650

The use of NMR in the undergraduate curriculum provides opportunities to create significant learning experiences for students from their freshman year through the time of graduation. We describe how Saint Vincent College has incorporated NMR based experiments and activities in general chemistry, organic chemistry, and biochemistry in a manner that provides students with a range of NMR experiences and fosters connections between chemical concepts across a course and between courses.

Introduction

Since its initial development in the 1940's, NMR has become one of the most important methods for determining the structure of molecules. As described in the recent National Research Council report Beyond the Molecular Frontier: Challenges for Chemistry and Chemical Engineering (/), NMR has revolutionized how chemists determine the structure of molecules in solution, in solids, and even in the human body. Four Nobel prizes have been awarded for work related to NMR - Felix Bloch (1952 - Physics), Ε. M. Purcell (1952 Physics), Richard Ernst (1991 - Chemistry), Kurt Wuthrich (2002 - Chemistry), Paul Lauterbur (2003 - Medicine/Physiology), and Sir Peter Mansfield (2003 Medicine/Physiology). Even the guidelines for undergraduate professional education developed by the American Chemical Society's Committee on 8

© 2007 American Chemical Society

In Modern NMR Spectroscopy in Education; Rovnyak, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.


9 Professional Training single out NMR when they state "Nuclear magnetic resonance spectroscopy has become an indispensable experimental method for chemistry. Approved chemistry programs must have an operational NMR spectrometer." (2) The central importance of NMR is reflected in the number of articles published in the Journal of Chemical Education that use this technique. Since mid-1995, 444 articles have been published in the Journal that have NMR as a keyword. A similar search of the Project Chemlab database, which includes laboratories published in the Journal, gave 315 results; 165 were laboratories for organic chemistry while 48 were for inorganic chemistry and 42 were for physical chemistry. While the application of NMR in individual courses is well established in the undergraduate chemistry curriculum, we believe that NMR has the potential to serve as a unifying and integrative thread as well. Our experience at Saint Vincent College has helped us see that thoughtful incorporation of NMR throughout the undergraduate curriculum can be a major tool in the creation of significant learning experiences for undergraduate students.

What Characterizes Best Practice and Significant Learning in Undergraduate Education? Much attention has been directed over the last 15 years as to what characterizes both significant learning experiences and "best practice" in undergraduate science education. Project Kaleidoscope, a major leader in this work, has described(J) "what works" in undergraduate science education as being characterized in part by: • learning that is experiential and places great emphasis on investigation throughout the curriculum, starting with the veryfirstcourse. • learning that is personally meaningful for students and faculty, that makes connections to other fields, and that can be linked to practical applications The much cited report How People Learn produced by the National Research Council in 1999(4) identified the following as essential to effective learning: • an environment centered on learners and that is designed to "help students make connections between their previous knowledge and their current academic tasks." • teaching knowledge in multiple contexts rather than in just a single context. The use of multiple contexts for learning helps students identify the relevant features of concepts in a more flexible manner. And thefinalreport issuedfromthe 2003 "Exploring the Molecular Vision" conference sponsored by the ACS Society Committee on Education stated as



10 part of the conference's conclusions regarding preparation for the profession that "problem solving is one of the most empowering learning experiences for science students" and "a deep knowledge of chemistry and the ability to pursue cutting-edge chemical research in teams have become even more central to innovation at the forefront of science and technology."(5). The incorporation of NMR throughout the undergraduate curriculum offers several ways to achieve these characteristics. NMR is a technique that is both "hands on" and at the same time potentially involves a substantial body of theory to interpret different types of experimental results. The multiple levels of information contained in an NMR spectrum and the variety of ways that NMR can be used provide a data-rich environment for students to work in. Using NMR to make connections between different chemistry courses, various subdisciplines of chemistry, or chemistry and other disciplines is relatively straightforward. Analysis of spectral data is clearly a problem solving activity and one that can be constructed at varying levels of difficulty. And using NMR in multiple courses provides students with an opportunity to see the same fundamental chemical concepts in different contexts. In Designing Significant Learning Experiences (6), Dee Fink puts forth a taxonomy of significant learning that includes six different types of learning. Among the kinds of learning that make up the taxonomy are foundational knowledge (facts, terms, concepts, principles), application (problem solving and decision making) and integration (making connections among ideas, subjects, etc.). Using NMR across the undergraduate curriculum clearly helps students develop foundational knowledge and engage in a variety of applications. At the same time, NMR also offers possibilities in regards to how students integrate the ideasfromvarious courses. Biology majors who first encounter NMR in organic chemistry and then encounter it again in biochemistry are likely to see the connections between the two disciplines differently than students who only encounter NMR in organic chemistry. For all of the reasons given here, we believe that it is in every chemistry department's best interest to explore collaboratively how NMR can be incorporated throughout the undergraduate curriculum.

NMR in the Saint Vincent College Chemistry Curriculum Saint Vincent College is a Catholic liberal arts college enrolling approximately 1500 undergraduates. In 1998, the Chemistry department at Saint Vincent College began a comprehensive program for ongoing assessment of student learning and continuous program improvement that includes alumni surveys, a comprehensive laboratory practicum, and assessment of senior theses and presentations. The assessment indicated that our graduating seniors had inadequate preparation in the area of spectral interpretation, especially NMR spectroscopy. In addition, the assessment results showed that students had a limited exposure to two-dimensional and multi-pulse NMR techniques. In the



11 spring of 2003 we received a CCLI-Adaptation and Implementation grant from NSF to integrate FT-NMR throughout our curriculum by purchasing the Anasazi EFT-NMR upgrade for our 60 Mhzfixedmagnet. There were several goals that we had at the onset of this project. We believed it was important that students in all science, technology, engineering, and math majors would have a basic understanding of the uses of onedimensional NMR spectroscopy. In addition, we wanted all biology and chemistry majors to be able to operate an FT-NMR and interpret proton, carbon, DEPT, COSY, and HETCOR spectra. Finally, we wanted our chemistry majors to be able to choose the appropriate NMR experiments to address specific experimental needs. To accomplish these goals we have, over the past two years, incorporated a series of experiments into general chemistry, organic chemistry, and thefirstsemester of biochemistry.

General Chemistry Students in general chemistry are introduced to NMR through an activity that focuses on the concepts of NMR activity and nuclear structure, bond polarity, and chemical shift. Earlier work published in the Journal of Chemical Education by Davis and Moore described how Mercer University had incorporated FT-NMR into general chemistry through an experiment that studied electronegativity through the additive effects of halogens on the ^chemical shift of methane (7). While we opted to use a similar approach, we chose to connect these concepts to the determination of protein structure through closer examination of chemical shifts in amino acids. In addition, we chose to use the POGIL approach for this activity. POGIL (process oriented guided inquiry learning) is a pedagogical approach that seeks to "simultaneously teach content and key process skills such as the ability to think analytically and work effectively as part of a collaborative team." (8,9) The activity we developed starts with a review of bonding, dipole moments, and Lewis dot structures. Students are then asked to determine the number of protons and neutrons of 3 NMR active and 3 NMR inactive nuclei. From this, students are asked to devise a rule for determining whether or not a particular nuclei is NMR active. In the next phase of the activity, students are asked to compare the chemical shift of methylene protons next to a halogen for a series of alkyl halides that differ in the number and chemical identity of the halogens. From this data students are asked to construct a plot of H chemical shift as a function of the sum of electronegativities for the atoms attached to a single carbon. Figure 1 shows a typical plot constructed by students as part of this activity. Finally, students are asked to apply their model to an amino acid by determining the chemical shift of a proton attached to thefirstcarbon in a side chain and evaluating the polarity of the side chain as a whole. Amino acids uses for this activity include alanine, valine, leucine, serine, cysteine, threonine, and phenylalanine. !



Organic Chemistry l

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Students in organic chemistry are introduced to H, C, and DEPT NMR spectroscopy in the first semester laboratory course. These techniques are used throughout the first semester as the primary means for structurally characterizing compounds. In the second semester lab, students are introduced to 2D NMR through the use of COSY to identify an unknown. Branz and colleagues published an experiment in the Journal of Chemical Education (10) where they described what they called a "double unknown" experiment where students use a unknown alcohol and an unknown carboxylic acid to synthesize an ester whose structure is unknown. COSY spectroscopy was then used to determine the structure of the product. While we found this experiment very attractive for several reasons, we saw one difficulty. Because ester synthesis is not covered in the typical sophomore organic course until late in the spring semester, using the experiment as published would mean that students taking organic chemistry would not encounter 2D NMR until late in the year. To allow us to introduce 2D NMR earlier in the spring semester, we modified this experiment so that students synthesize an unknown ether using reagents whose structure is not known to the students. Otherwise, we implemented this experiment as Branz and colleagues describe it. To provide additional opportunities to work with spectral data and how structure and spectroscopy are related, students in the spring semester are given problem sets that require them to develop synthetic routes for compounds such as Albuterol, Atenalol, Ibuprofen, and Prozac. As part of these problem sets, students are given NMR spectral data that they must work with in order to


13 answer some specific questions. The details of what NMR data is given and what students are asked to do with it variesfromproblem set to problem set. In one case, students are asked to predict the chemical shift, splitting pattern, and integration in the *H NMR for ibuprofen alcohol, an immediate precursor to ibuprofen. Students then are asked to assign all the peaks in the H and C NMR for ibuprofen itself. In another problem set, students are given the structures of two components found in cough medicine along with the COSY spectrum for one of the drugs. Students are asked to draw the correct structure of the molecule and assign all of the protons other than -OH and -NH. Downloaded by INDIANA UNIV BLOOMINGTON on May 9, 2015 | http://pubs.acs.org Publication Date: August 16, 2007 | doi: 10.1021/bk-2007-0969.ch002

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Upper Level Courses The fall semester biochemistry course at Saint Vincent focuses heavily on experimental techniques in protein chemistry. To provide students with "handson" experience in the process of determining the three dimensional structure of a protein, we have incorporated into that course the experiment published by Rehart and Gerig in the Journal of Chemical Education (77). In this experiment, datafrom1D-NMR, COSY, TOCSY, and NOES Y are used to develop a three dimensional model for the structure of the octapeptide angiotensin in DMSO. Through a web site, the authors provide spectra that they collected on a 300 MHz instrument. We ask our students to engage in the "paper and pencil" process of assigning peaks in the 1D-NMR, COSY, and TOCSY spectra. Then students use those peak assignments to examine NOESY spectra for information that will provide distance constraints for the model. While Rehart and Gerig do give information on how students can collect the data themselves on a high field instrument, that aspect isn't possible for us using the Anazasi setup. To utilize "dead time" while other experiments (such as chromatographic separations) are running, we spread this activity out over a period of roughly four weeks. In the near future we plan to incorporate another NMR experiment in the fall biochemistry lab course. This experiment, originally published by Giles et al. in the Journal of Chemical Education (72) uses C NMR as a means to track metabolic flux through glycolysis in yeast cells grown under different osmolarities. As the external osmolarity of the growth medium is altered, the cells respond by shifting the balance among metabolic pathways such that the ratio of C labeled ethanol to C labeled glycerol changes. We see this experiment as a nice complement to the protein structure activity we already use, and a pedagogically sound way to introduce students to the use of NMR as a probe for the dynamics of metabolic pathways. Advanced Physical Methods is a project-based laboratory course formed by integrating elements of what were originally separate courses - Physical Chemistry II Laboratory and Instrumental Laboratory - into a single course. The NMR experiment we plan to incorporate into this course will be a kinetics experiment, either esterification of trifluoroacetic acid (13) or hydrolysis of an 13

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14 orthoester (14), with NMR used as the primary means of measuring reaction rate. Table I provides a summary of the various NMR activities that are being incorporated into the four year curriculum at Saint Vincent College.

Table I. NMR activities in the Saint Vincent chemistry curriculum Downloaded by INDIANA UNIV BLOOMINGTON on May 9, 2015 | http://pubs.acs.org Publication Date: August 16, 2007 | doi: 10.1021/bk-2007-0969.ch002

Course general chemistry organic chemistry

Assessment

Activity

student worksheet correlating chemical shift with electronegativity structure determination using lab reports problem sets lD^H, C) and 2D COSY spectra structure determination using lab reports TOCSY and NOESY, metabolic analysis using in vivo NMR lab reports reaction kinetics monitored by NMR ability to interpret spectra and lab skills determine structure assessment exam 13

biochemistry

other upper level courses end of undergraduate education NOTE:

Activities in italics are in process of being incorporated into curriculum at time this chapter was written.

What Have We Learned? Three years after receiving the grantfromNSF, we have learned several things that we believe will be of use to other departments seeking to integrate NMR throughout the undergraduate curriculum: Don't expect to do everything at once. This statement applies equally to the implementation of new experiments and how students are introduced to the concept of NMR. In terms of introducing new experiments, we have successfully implemented more than half of the experiments that we eventually expect will be part of our curriculum. Still to be incorporated into our Advanced Physical Methods course is a kinetics experiment using NMR, and a metabolic experiment in the biochemistry lab that uses C NMR to track flux through glycolysis in yeast cells. 1 3



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In the same manner, we have found that NMR concepts are probably best introduced in small blocks, with opportunities for practice worked in wherever possible. Our General Chemistry activity focuses very heavily on chemical shift and ignores other important topics like splitting or the explanation of NMR in terms of bulk magnetization vectors. The angiotensin activity in biochemistry lab assumes some prior exposure to basic 2D NMR techniques. Not all NMR related activities require having students physically colle the data; sometime pencil and paper is equally effective. If we insisted that General Chemistry students actually run their own NMR, we would be concerned about the potential confusion and clouding of learning that might develop. If we insisted that students in the biochemistry lab had to collect their own spectral data to determine the conformation of angiotensin, we would never be able to incorporate this experiment into our curriculum. "Paper and pencil" activités can be just as thought-provoking and demanding of critical thinking and problem solving skills as an activity where students collect the data themselves. The key is how the assignment is designed so that it both builds on prior learning and challenges students to use concepts in new ways or new contexts. An assessment process can provide valuable information and feedbac Our department assessment plan initially helped us see more clearly the weaknesses that our graduating seniors had in regards to NMR and helped us make a stronger case for the resources necessary to implement NMR throughout the curriculum. Three years into this project, we have seen significant increases in the percentage of graduating seniors who can assign the correct structure for a given set of NMR data. We also observed that students who encountered our revised curriculum starting in their sophomore year were more successful as seniors in correctly determining a structurefromNMR data than they were as second semester sophomores. This result suggests that student mastery of NMR concepts and skills required both time and encountering NMR in multiple settings. Our hope is that assessment will provide insight into what students actually learn in this area so that we can, in an informed manner, make any needed modifications. Our goal has always been to integrate NMR into our curriculum so that it fosters significant learning, so a carefully thought out assessment strategy provides a way to understand "what works" and what needs revision.

Assessment of Student Learning The question of assessment is one that many chemistry faculty struggle with, and so it is worth looking more closely at this issue in the context of NMR and pedagogy. Student learning related to NMR has the potential to be particularly challenging, as it involves a complex mixture of laboratory skills, conceptual understanding, and problem solving abilities. But that also means



16 that student learning related to NMR offers some unique assessment opportunities. The National Research Council report Evaluating and Improving Undergraduate Teaching in Science, Technology, Engineering, and Mathematics (15) strongly encourages faculty to use outcome assessment as the basis for determining what students have learnedfroma unit, a course, or a series of courses. Outcome assessment starts with the articulation of student learning objectives worded in terms of what students will be able to do after learning the material in question. After the goals have beenframedin terms of student learning, then appropriate assessment measures are utilized. Walvoord has pointed out that the grading of student work can be a valuable assessment tool if criteria used to evaluate the work are made explicit (16, 17) The most systematic way to accomplish this is the approach known as "primary trait analysis", which is described in more detail in several sources (75, 77). In using primary trait analysis, an instructor first identifies the traits that he or she feels are most important to evaluate, then develops a scoring system (typically two to five points) for each trait. The result is a rubric that provides explicit criteria for evaluating student work and that can readily be communicated to other parties such as students, accrediting bodies, or organizations such as the National Science Foundation. We are beginning to think about how we might develop some resources for primary trait analysis of student work involving NMR that could be used by various members of the department. While primary trait analysis is the approach to grading student work that most effectively connects with assessment, it is not the only assessment strategy that should be considered. Much recent research in cognitive science has demonstrated the importance of formative assessments in helping students learn more effectively. Formative assessment, which is provided morefrequentlyand immediately than the traditional summative assessments such as exams, can be a powerful tool for both helping to reinforce student understanding of NMR concepts and addressing student misconceptions in a timely fashion. Our efforts at providing formative assessment have focused on both the use of assignments that involve using NMR concepts and data - such as the OTC drug synthesis problems described above - as well asfrequentuse of NMR in lab reports. Grant Wiggins (18) has called for the use of authentic tasks in the process of assessment because they serve to provide direction, coherence, and motivation for the work involved in learning. NMR is particularly amenable to being assessed in the context of authentic tasks. Consider a project-based laboratory where in the later stages students must decide which NMR experiments to run in order to unambiguously determine the structure of a compound. This is a task that is both authentic (something chemists routinely do in their work) and provides instructors with the opportunity to gather information as to the reasons why students chose particular techniques and how they interpreted the data. We have found this approach to assessment particularly valuable in our work at Saint Vincent. Experiments such as the



17 "double unknown" synthesis of an ether and the determination of the 3D structure of angiotensin involve using NMR concepts and data in the same manner as research scientists. In addition, our department's assessment of the laboratory skill level of graduating seniors requires students to interpret NMR spectra that are given to them by the faculty, rather than simply answering questions in an exam format. This also more closely mirrors how chemists routinely use NMR concepts and data in their own work. In addition to direct measures of student learning such as the ones described in the preceding paragraphs, indirect measures can also be useful in the context of NMR. Asking students how much they thought they learned, can be useful in gathering information about what students have learned over a longer period of time - a series of courses or an entire four year curriculum. A particularly useful indirect measure is the Knowledge Survey developed by Nuhfer and Knipp (19), which could be used with seniors to gather some evidence as to what they feel they have learned about NMR over the course of their entire undergraduate experience. We are exploring the possibility of incorporating a Knowledge Survey that would include questions specific to NMR as part of our department's assessment of graduating seniors.

Conclusions

The past ten years have seen a number of reports, including the National Research Council's Transforming Undergraduate Education in Science, Mathematics, Engineering, and Technology (20) and BIO 2010: Transform Undergraduate Education for Future Research Biologists (21), that have calle for reforms in undergraduate science education that focus on inquiry-based activities and interdisciplinary connections. The incorporation of NMR throughout the undergraduate curriculum offers unique opportunities to address these challenges in ways that challenge students, engage them in the process of doing science, and making connections between various scientific disciplines. In addition, NMR-based activities lend themselves to using a variety of assessment approaches to gather information about student learning. Our ongoing experience at Saint Vincent College has shown us that incorporating NMR across the undergraduate curriculum can lead to significant improvements that ultimately help our students develop a better understanding of chemistry and its role in scientific research.

Acknowledgements The work described in this article was supported in part by NSF-CCLI-A&I Grant #0310756 and a grant from the Spectroscopy Society of Pittsburgh.


18 References 1.


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20. National Research Council Committee on Undergraduate Science Education. Transforming Undergraduate Education in Science, Mathematics, Engineering, and Technology; National Academy Press: Washington, DC, 1999 21. National Research Council Board on Life Sciences. BIO 2010: Transforming Undergraduate Education for Future Research Biologists; National Academy Press: Washington, DC, 2003


Enhancing Undergraduate Pedagogy with NMR across the Curriculum

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