Structural Bioorganic Chemistry
Advanced formation in the area of structural analysis of organic compounds with resource to nuclear magnetic resonance and X-ray Crystalography. This course has a special emphasis to the application of modern NMR techniques as well as monocrystal X-ray cristyalography techniques for structural elucidation and for the study of intermolecular interactions in a biological context.
At the end of the course the student should be able to: (1) acquire, process and interpret multidimensional NMR spectra as well as X-ray data. (2) plan strategies to the elucidation of complex structural problems, including the determination and validation of structures, conformational analysis and intermolecular interaction studies ("drug screening") (3) integrate and combine NMR and X-ray data with the courses of Organic Chemistry and Computational Chemistry (4) learn to use several computational on line tools as well as programs for molecular visualization and representation.
These skills will be explored in a context of original applications in a research environment.
Eurico José da Silva Cabrita
Weekly - 3
Total - 49
Basic knowledge in Physical-Chemistry, organic chemistry, spectroscopy and introductory training in Nuclear Magnetic Resonance spectroscopy.
1.High-Resolution NMR Techniques in Organic Chemistry, T. D. W. Claridge, Tetrahedron Organic Chemistry Series, Volume 19, Pergamon Press 1999.
2.Ressonância Magnética Nuclear - Fundamentos, métodos e aplicações, Victor M. S. Gil, Carlos F. G. C. Geraldes, 2ª Edição, Fund. Calouste Gulbenkian, Lisboa, 2002.
3. Spectrometric Identification of Organic Compounds, R. M. Silverstein, F. X. Webster, D. J. Kiemle, David L. Brice, 8th Edition, John Wiley & Sons, 2014
1.Crystal Structure Analysis for Chemists and Biologists, J.P. Glusker, M. Lewis e M. Rossi, VCH: New York, 1994.
2.Crystallography Made Crystal Clear, G. Rhodes, 2nd Ed., Academic Press, San Diego, London, 2000.
3.Crystal Structure Determination, W. Clegg, Oxford Chemistry Primers, Oxford University Press, USA, 1998.
The course will be taught through problem solving (TP) classes (1 x 3.5 hours per week) and practical sessions (3 sessions of 3,5 hours).
In TP classes by solving oriented problems students are exposed to the theoretical program of UC. When necessary computer programs are used to illustrate three-dimensional molecular modeling concepts of stereochemistry and conformational analysis. Students are encouraged to use their own personal computers and to use a number of tools available on the internet.
Practical lessons hours correspond to laboratory classes. Laboratory classes intend to introduce the student to sample preparation, acquisition and processing of NMR and X-ray data.
Assesment of the UC will be according to the following:
Seminars - 40 %
Tests - 60 %
Mandatory presence in 2/3 of the T sessions, practical classes and seminars.
Students will be evaluated through 2 tests, the weekly delivery of solved problems, a questionnaire related to the practical class and the presentation of a seminar, with the following weighting for the final grade:
Average of the 2 tests - 50%
Weekly delivery of problems - 10%
Practice Questionnaire - 10%
Seminar presentation - 30%
There is no minimum grade.
For approval it is necessary to have a final result of 9.5.
- Review of general concepts in NMR.
- Introduction to 2D techniques. Homonuclear correlation: COSY and TOCSY. Heteronuclear correlation HMQC , HSQC and HMBC. Correlation across space: nuclear Overhauser effect, NOESY, ROESY.
- Dynamic NMR and Chemical Exchange.
- Integrated strategies for structural analysis using NMR, mass spectrometry, infrared spectroscopy and EPR spectroscopy: case studies.
- Studying Intermolecular interactions with NMR. Drug- screening techniques and Structural activity relationship (SAR) by NMR . Introduction to biomolecular NMR .
- Introduction to structural analysis by X- ray diffraction . X-ray diffraction of single crystal . Geometric principles of diffraction and Bragg''''''''''''''''s law . Reciprocal space and the Ewald sphere .
- Collection of diffraction data. Methods for solving the "phase problem". Anomalous dispersion, determination of absolute configuration. Refinement of the structure and geometric characterization. Crystallographic databases.