SFKKM9031U Advanced Spectroscopy

Volume 2013/2014
Education
MSc in Pharmaceutical Sciences - elective, MSc in Medicinal Chemistry - elective, Cand.Scient.Pharm. - elective, Cand.Pharm. - elective
Content
Course emphasis is on practical problem solving using examples from textbooks as well as from the teacher's own research. The course will illustrate ways of using different spectroscopic methods to determine structure and identify small to medium-size organic compounds.

Theory behind NMR spectroscopy will be briefly introduced using the vector model. Fourier transform NMR methods will be described. There will be a thorough introduction to basic NMR parameters such as integrals, coupling constants and chemical shift values for 1H and 13C, including first order and simple second order analysis of coupling patterns. Spectral editing will be illustrated with DEPT experiments. Modern 2D NMR experiments will be described, and the students will become familiar with the use of various 2D NMR techniques to extract structural and stereochemical information using through-bond and through-space correlations. Teaching will be integrated with the use of computer programs for data processing and analysis.

The mass spectrometry segment will review various ionisation methods, mass separation techniques, and ion fragmentation patterns.

Chiroptical methods (ORD and CD) for determining absolute stereochemistry will be introduced.
Learning Outcome

Formål / Objective

Spectroscopic methods of structure elucidation and characterization are of profound importance in connection with organic synthesis, work with pharmaceuticals and their metabolites, with biochemicals, natural products, foods and food additives, endogenous and environmental toxins, biotechnology products, etc. Spectroscopic methods are therefore of interest for students, researchers, and other personnel working in many areas of pharmaceutical, natural, life and health sciences.

The course introduces students to understanding and practical applications of modern spectroscopic techniques. The course focuses on methods used to determine structures of organic compounds, comprising determination of atomic composition, atom connectivities, and relative stereochemistry, as well as data processing and data analysis using modern spectroscopic software.

Målbeskrivelse / Course outcome

Students will learn to use advanced NMR spectroscopic techniques and mass spectrometry for structure elucidation of complex organic compounds, including spectra assignment. At the end of the course, students should be able to:
  • Interpret first order coupling patterns as well as simple second order coupling patterns in 1H NMR spectra
  • Predict and interpret 1H and 13C NMR chemical shift values for small to medium size organic molecules and use them to solve structural problems
  • Interpret homo- and hetero nuclear 2D NMR experiments such as COSY, NOESY/ROESY, HSQC and HMBC to deduce structural fragments and their connections
  • Explain fragmentation patterns in EI mass spectra and to be familiar with other techniques/ionization forms of mass spectrometry.
In addition, students are expected to be able to select suitable spectroscopic experiments, alone or in combination, to solve various structural and stereochemical problems, including sample preparation, to perform independent structure elucidation work with a complex molecule based on a set of spectra, and to communicate the results using standard spectroscopic terminology.
Literature
  • J.B. Lambert, S. Gronert, H.F. Shurvell, D. Lightner, R.G. Cooks, Organic Structural Spectroscopy, 2nd international edition, Pearson 2011.
  • Handouts, exercises and assignments prepared by the teachers are available at the course home page.
Students should have knowledge of organic chemistry, including stereochemistry (configuration and conformation) and electronic structure (resonance and inductive effects) of organic molecules. Furthermore, students should have a knowledge corresponding to elementary courses in organic spectroscopy at the level taught in organic chemistry textbooks (basic principles and IR, UV, MS and 1D NMR spectra of simple organic molecules).
For the first 6 course-weeks the course will consist of 2 x 2 hours lecture to introduce basic understanding of theory, followed by 2 x 2 hours theoretical exercises to practice problem solving and 4 hours computer exercises to practice data handling and solving more complex problems. In course-week 7 a three-week exam project will start, and thus the lectures, theoretical exercises and practical exercises will be reduced to 2, 2, and 4 hours, respectively, in this week, whereas course-week 8 and 9 will only involve project work.
  • Category
  • Hours
  • Lectures
  • 28
  • Practical exercises
  • 28
  • Preparation
  • 77
  • Project work
  • 45
  • Theory exercises
  • 28
  • Total
  • 206
Credit
7,5 ECTS
Type of assessment
Written assignment
Prøveform / Examination type:
Report based on a three-week examination project. Based on MS and raw 1-D and 2-D NMR data, which have to be processed by the students using appropriate software, the aim of the project is to determine the structure of a complex organic molecule (typically 15-30 carbon atoms and a number of stereocenters), to present a complete (as far as possible) assignment of spectroscopic parameters, and to provide an in-depth interpretation of the available spectra. The student will conduct this work in groups of two. Finally, each student will prepare an individual report - written and formatted as a scientific article.

Prøvedesign / Examination design
During the three-week examination project, students will apply their acquired knowledge to solve a relatively complex structure elucidation problem. The problem will be based on authentic spectroscopic data, which will have to be processed and analyzed using the software available during the course. Although problem solving will be performed in groups of two students, the understanding of the subject matter and the ability to communicate the results will be tested via individual reports.

The final project will consist of the following step:
Download of raw data from a server (groups of two students).
Processing of the data (Fourier transformation, phasing, calibration, integration) and plotting (groups of two students).
Interpretation of the data, elucidation of the structure (groups of two students).
Preparation of a written report (individual; guidelines aimed to ensure the authenticity of this part of the work will be provided).
During the three-week examination project period, each student is entitled to up to 30 minutes of individual consultation with a teacher. However, extensive need for consultation on basic issues can affect the final mark negatively.
Aid
All aids allowed
All aids are permitted during the examination project. Students are entitled to the confirmation of elemental composition found for their unknown compound before proceeding with the project. In addition, students are entitled to up to 30 min of individual consultation during the project period
Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assesment

Beskrivelse af prøven og bedømmelse / Description of examination and assessment criteria

Beståkrav / Pass criteria

The report must illustrate the logic of structure elucidation and interplay of various spectroscopic techniques for reaching the final result. Mechanical description of one spectrum a time is less satisfactory. The report should be brief, yet address all essential points. Guidelines for the report as well as example of a satisfactory report will be provided.

Karakterbeskrivelse / Description of grades

12 - Excellent performance
Is given for an excellent report showing that the student’s knowledge corresponds to meeting all course aims with only a few and relatively unimportant limitations. The structure elucidation work was done fully independently, essentially without seeking help from the teachers. The report shows that the student is able to focus on correct spectroscopic experiments to derive relevant information, and that he or she masters the spectroscopic nomenclature to communicate all necessary points.

7 - Good performance
Isgiven for a good report that reaches correct conclusions regarding interpretation of various spectra, but with shortcomings regarding interpretations and explanations. Only the most important course aims are met. During the three-week project period the student needed help with issues that he or she should be familiar with from following and understanding the instructions during the course. Spectroscopic nomenclature is used in the report, but not without mistakes.

02 - Acceptable performance
Isgiven for a barely satisfactory report. The structure is elucidated correctly, but the interpretation and the discussion show that knowledge of various experiments and their use is superficial, and the report lacks the logical interplay of various spectroscopic techniques. The full amount of allowable help was given during the project. This and the report itself show that the student missed important points during course teaching.