SFKKM9031U  Advanced Spectroscopy

Volume 2017/2018
Education

MSc Programme in Pharmacy or Pharmaceutical Sciences (Danish programmes cand.pharm and cand.scient.pharm) - elective

MSc Programme in Medicinal Chemistry - elective

MSc Programme in Pharmaceutical Sciences (English programme) - elective

Content

Spectroscopic methods for structure elucidation of organic compounds are of profound importance in many areas of pharmaceutical-, natural-, life- and health sciences. The course introduces students to basic theory and practical applications of modern spectroscopic techniques; with emphasis on practical problem-solving for small-molecule organic compounds and peptides.

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. Strengthening of IT competencies will be an integral part of the course by the use of computer programs for data processing and analysis.

For mass spectrometry, emphasis will be on various ionisation methods, mass separation techniques, and ion fragmentation patterns.

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

Learning Outcome

Students will learn to use advanced NMR spectroscopic techniques and mass spectrometry for structure elucidation of complex organic small-molecules and peptides.

At the end of the course, students are expected to be able to:

Knowledge:

  • Possess knowledge about basic NMR theory, i.e., vector model, chemical shit, integrals and coupling patterns, and their implication in spectral assignment and structure elucidation.
  • Possess knowledge about ionization sources and fragmentation patterns in mass spectrometry.
  • Be acquainted with hyphenated spectroscopic techniques, chiroptical methods and NMR methods for determination of absolute stereochemistry.

 

Skills:

  • 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 heteronuclear 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.

 

Competencies:

  • independently select suitable spectroscopic experiments, alone or in combination, to solve various structural and stereochemical problems
  • perform structure elucidation of complex molecules based on spectroscopic data sets - and to communicate the results in scientific manuscripts using spectroscopic terminology.
  • J.B. Lambert, S. Gronert, H.F. Shurvell, D. Lightner, R.G. Cooks, Organic Structural Spectroscopy, 2. Pearson new international edition of 2nd revised edition, Pearson 2013.
  • 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 there will only be 2 hours of lectures and 2 hours of theoretical exercises in this week, whereas course-week 8 and 9 will only involve project work.
Credit
7,5 ECTS
Type of assessment
Written assignment
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.

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

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 at 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.

To achieve the grade 12 the student must be able to:

Knowledge:

  • Possess knowledge about basic NMR theory, i.e., vector model, chemical shit, integrals and coupling patterns, and their implication in spectral assignment and structure elucidation.
  • Possess knowledge about ionization sources and fragmentation patterns in mass spectrometry.
  • Be acquainted with hyphenated spectroscopic techniques, chiroptical methods and NMR methods for determination of absolute stereochemistry.

 

Skills:

  • 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 heteronuclear 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.

 

Competencies:

  • independently select suitable spectroscopic experiments, alone or in combination, to solve various structural and stereochemical problems
  • perform structure elucidation of complex molecules based on spectroscopic data sets - and to communicate the results in scientific manuscripts using spectroscopic terminology.
  • Category
  • Hours
  • Lectures
  • 26
  • Theory exercises
  • 26
  • Practical exercises
  • 24
  • Preparation
  • 85
  • Project work
  • 45
  • Total
  • 206