Monash University Handbook 2010 Undergraduate - Unit

Synopsis

The subject expands on the use of spectroscopic and spectrometric techniques and their applications in medicinal chemistry. The use of two dimensional NMR in the identification and characterisation of more complex compounds is introduced. Techniques for the assignment of spectra for more complex molecules will be described and the application of NMR spectroscopy to larger biomolecules will be introduced. The use of NMR spectroscopy to measure the interaction of drugs with biological molecules and the energetic factors which drive the processes of drug-receptor interaction will be described.

The uses of mass spectrometry in Medicinal Chemistry will also be expanded upon. After a review of structural elucidation via mass spectrometry, and a brief survey of ion source and mass analysis techniques, we will also cover applications of hyphenated techniques such as GC-MS and LC-MS to the study of medicinal compounds. The MS of additional compound classes such as carbohydrates, lipids, amino acids, peptides, and proteins will be considered as well as strategies for effective use of MS in proteomics.

Circular dichroism (CD) spectroscopy will also be covered, particularly in regard to its use in the determination of the secondary structure in proteins and nucleic acids. Raman spectroscopy, and more advanced techniques in IR spectroscopy techniques will be introduced. The quantum chemistry and photophysics which forms the basis of electronic spectroscopy techniques will be explained, with an emphasis on fluorescence and its application to proteins.

This will involve:

• Thermodynamics
• Advanced NMR Spectroscopy
• Mass Spectrometry and associated techniques
• Optical Spectroscopy

Objectives

After completing this unit students will be expected to be able to:

1. Analyse and interpret two dimensional spectra so as to identify the chemical structures of compounds;
2. Define the term Nuclear Overhauser Enhancement (NOE) and account for the observation of NOEs in one-dimensional and two-dimensional NMR spectra of both small and large molecules;
3. Analyse and interpret NOE data to determine the conformation of small molecules;
4. Analyse and assign two-dimensional NMR spectra of small peptides;
5. Describe quantitatively the relationship between enthalpy, entropy and free energy;
6. Describe quantitatively the relationship between changes in free energy and equilibrium;
7. Apply the concepts of this thermodynamics module to selected examples of biochemical energetics, protein-drug binding and drug-receptor interactions;
8. Describe the principal NMR-based strategies for drug discovery and design;
9. Use mass spectral data for structural elucidation;
10. Understand how to select an appropriate ion source method for a mass spectral study of a compound;
11. Understand and select among the various methods for mass analysis, and the use of collision-induced dissociation (CID) to solve structural problems involving biomolecules;
12. Describe the use of GC-MS and LC-MS for the study of pharmaceuticals and drugs;
13. Analyse mass spectral fragmentation patterns for important compound classes including carbohydrates, lipids, amino acids, peptides, and proteins.
14. Use and interpret mass spectral data for proteomics;
15. Describe how circular dichroism spectroscopy is useful for elucidation of secondary structure in proteins and nucleic acids;
16. Describe sampling methods and instrumentation available for IR and Raman spectroscopy and select the most suitable techniques for various applications on an informed basis;
17. Detail the factors which govern photon-initiated electronic excitation, and describe the processes by which molecules can relax. In particular, to describe the phenomena and applications associated with fluorescence;
18. Apply their knowledge of quantum theory and photophysical processes to interpret electronic and vibrational spectra;
19. Measure and record data relevant to the understanding of drug structure and reactivity;
20. Perform numerical calculations based on experimental or theoretical data;
21. Present written or oral results of experimental work.

Assessment

Final exam (2.5 hour): 60%; mid-semester exam: 20%; practical assessments: 20%.

Chief examiner(s)

Dr Martin Scanlon

Contact hours

24 1 hour lectures, 12 1 hour tutorials and nine 4 hour practicals

Prerequisites

VPS2082 Introduction to Spectroscopy

Additional information on this unit is available from the faculty at:

http://www.monash.edu.au/muso/support/