3 credits 45 theoretical hours
OBJECTIVES:
Provide students with knowledge about NMR techniques and their various applications in Organic Chemistry and Biochemistry
SUMMARY:
1. Relaxation.
2. Studies with isotopic ratio.
3. Ligand-protein interactions.
4. Studies of biological fluids.
5. Dynamic NMR.
6. NMR in drug development
PROGRAM CONTENT:
1. Relaxation
1.1. spin-lattice and spin-spin relaxation
1.2. relaxation mechanisms
1.3. relaxation by chemical shift anisotropy
1.4. scalar coupling relaxation
1.5. spin rotation relaxation
1.6. relaxation by internuclear dipole-dipole interaction
1.7. influence of molecular movement on relaxation
1.8. correlation times
1.9. information about molecular dynamics through relaxation data
2.0. displacement reagents and applications
2.1 Nuclear Overhauser Effect and its applications
2.2 Biopolymers
2. Isotopic ratio studies
2.1. Origin of differences between different isotopes
2.2. Applications
3. Ligand-protein interactions
3.1. Use of NOE
3.2. Use of chemical shift perturbation
3.3. Field gradient pulsed NMR experiments
3.4. Diffusion experiments
3.5. Experiments by saturation transfer difference
3.6. Applications
4. Biological fluid studies
4.1. Metabolomic analysis with biological fluids
4.2. 1H and 13C chemical shifts of common metabolites and assignments
4.3. Suppression of the water signal and other signals
4.4. Multidimensional NMR and quantification
4.5. Multivariate statistical analysis
4.6. Applications
5. Dynamic NMR
5.1 Exchange of hydrogens between positions with different chemical shifts
5.2 Rotation barriers
5.3 Relationship with reaction kinetics
5.4 Application of double resonance to calculate reaction rates
5.5 Measurement of 1st order reaction rate by integration
5.6 Restricted internal rotation
5.7 Configuration inversion
5.8. Tautomery
6. NMR in drug development
6.1. Stages of drug development
6.2. Target validation and receptor identification
6.3. Structural strategy for drug development
6.4. Drug-receptor bonds
6.5. Prototype identification
6.6. Prototype Optimization
6.7. Preclinical studies: drug metabolism using biological fluids
6.8. Human trials
6.9. Purity of pharmaceuticals
6.10. Use of solid state NMR to
BIBLIOGRAPHY:
1. Sander, J.K.M. and Hunter, B.K. “Modern NMR Spectroscopy”; Oxford University Press, New York, 1987.
2. Abraham, R. J. and Loftus, P. “Proton and Carbon-13 NMR Specroscopy”; Heyden & Sons Ltd. 1980.
3. Lambert, J.B., Shurvell, H.F. Lightner, D.A. and Cooks, R.G. “Introduction to Organic Spectroscopy” Macmillan Publishing Company, New York, 1987.
