The subject "Structural Determination of Drugs" is an optional subject of the 5th year of the Degree in Pharmacy. It is located in the Chemistry module. Previously, in their first and second year, the students have completed the subjects Organic Chemistry and Advanced Organic Chemistry, related to the structure, properties and reactivity of organic compounds. In the third year of the degree, and within the same module, the students have completed the Pharmaceutical Chemistry course where the main methods for the design, synthesis and analysis of drugs are described.

To conclude with this module, the subject "Structural Determination of Drugs" deals with the application of spectroscopic techniques, such as Infrared, Nuclear Magnetic Resonance and Mass Spectrometry, to concrete examples, which will allow the students to understand the spectrum-structure correlation. The combined use of spectroscopic techniques is the best method for the interpretation of molecular spectra, and the determination of the structure of organic compounds, which are the main components of natural products and drugs.

Unlike most of chemical assays, the spectroscopic techniques are non-destructive and require a very small amount of sample, which is an advantage especially in the case of new or highly complex compounds

Consolidate the knowledge related to the application of different spectroscopic techniques for the analysis of organic structures.

Apply Spectroscopic Techniques for the Structural Elucidation of Organic Molecules and Drugs.

Determine the structure of polyfunctional compounds in view of the information obtained from the different spectroscopic techniques.

Acquire a solid base for the development of scientific research work.

1.Infrared spectroscopy. Basic concepts.

1.1.Introduction and applications

1.2.Infrared absorption theory.

1.3.Modes of vibration. Coupling between vibrations. Fermi resonance.

1.4.Selection rules

1.5.Instrumentation. Sample preparation. Accessories. Coupled techniques.

2.Infrared spectroscopy. Applications to qualitative analysis.

2.1.Characteristic frequencies

X-H stretching vibration region

Triple bond stretching vibration region

Double bond stretching vibration region

Fingerprint region

2.2.The effect of the substituents and the chemical environment on the absorption frequency.

Inductive effect

Bond strain

Hydrogen bonding

Conjugation

2.3.Empirical correlations to obtain information about structure

2.4.How to analyze IR spectra. Functional group identification.

3.Mass spectroscopy

3.1.General concepts. Instrumentation. Applications

3.2.Molecular ions. Isotopic abundance.

3.3.HRMS

3.4.Types of fragmentation reactions

3.5.Fragmentations in functional groups

4.Structure determination by Mass Spectroscopy.

4.1.General concepts. Mass spectrum analysis

4.2.Mass spectra of several types of compounds

5.Introduction to NMR Spectroscopy

5.1.Introduction

5.2.NMR Phenomenon.

5.3.Physical basis. Nuclear spin. Magnetic moment.

5.4.NMR instruments.

5.5.Chemical shift.

5.6.Fators affecting chemical shift.

5.7.Signal strength

6.Spin coupling

6.1.Spin-spin interaction

6.2.Magnetic equivalence.

6.3.Pople Nomenclature for coupled spin systems

6.4.First order and second order coupling.

6.5.Two spin systems. A2, AX and AB

6.6.Three spin systems. AB2 and AX2, AMX, ABX and ABC.

6.7.Four spin systems.

7.Coupling constants

7.1.Short and long distance coupling.

7.2.Coupling constant magnitude and sign

7.3.Geminal and vicinal coupling constant

7.4.Long distance coupling constant.

7.5.Structural elucidation.

8.13C NMR Spectroscopy

8.1.Introduction.

8.2.Record techniques and decoupling techniques.

8.3.Shift-structure correlations.

8.4.Coupling constants 13C-1H.

8.5.Structural elucidation.

Master classes will be used in which an overview of each of the spectroscopic techniques is given, discussing in the first place the theoretical principles to, later, study their applications with concrete examples. In order to settle the concepts, problems and exercises will be provided, that they students will develop individually or in groups. The resolution of the questions in the classroom will be carried out in a participative way.

The laboratory practices will consist of experimental work oriented to learn the spectroscopic techniques and the preparation of different types of samples. Cases with polyfunctional compounds will be carried out, where the joint use of all the technique is necessary for their identification, given their complementary nature. This part will be developed in groups, encouraging the formulation of questions, participation, discussion and teamwork.

• Continuous Assessment System
• Final Assessment System
• Tools and qualification percentages:
  • Written test to be taken (%): 55
  • Realization of Practical Work (exercises, cases or problems) (%): 15
  • Test IR/MS and RMN (%): 30

- Continuous evaluation: Throughout the course, there will be several written tests of the different topics (30%). To consider this note in the final grade, you must pass 70% in each of the tests and attend to at least 80% of the face-to-face activities. Otherwise, the whole subject will be evaluated in the final written exam

- Attendance to practical courses, work sheets and practical exam (15%).

- Extraordinary written final exam (55-85%). A 40% minimum in the final exam is mandatory prior to add the note at the practical courses to the final mark..

A 40% minimum in the final exam is mandatory prior to add the note at the practical courses.

In accordance with the regulations of the UPV/EHU, not taking the final evaluation test, whether ordinary or extraordinary, will mean the resignation of the call for evaluation and the qualification of the student will be recorded as a “No Show”.

The student who has previously completed the subject may either renounce to the continuous evaluation at other subjects from previous courses or renounce to the mixed evaluation in Structural Determination and face the whole evaluation in a single final test. In any case, the final test must certify THE ACQUISITION OF BOTH THEORETICAL AND PRACTICAL SKILLS.

The students who have completed the practical courses in the previous years will keep their note for a course (if it is higher than 0.75) and, even if they do not meet the 80% attendance requirement (that is, even if they have opted for the evaluation in a single final test) will have the right to carry out the practices attending always at 100% of the hours (except for reasons of force majeure). The student that chooses not to attend to the practical courses must pass a practical exam as part of the final test.

Protocol on academic ethics: During the development of the evaluation tests, the use of books, or notes, as well as phone, computer or other devices or devices will be prohibited [Only a calculator and spectroscopy tables without any type of mark are allowed]. In view of any case of dishonest or fraudulent practice in the evaluation tests or academic tasks the protocol on academic ethics academics at the UPV/EHU will be applied.

In the case a student does not pass the subject at the ordinary call, he/she can attend to the final test at the extraordinary call, where the same evaluation system used for the single evaluation will be applied.

- Attendance to practical courses, work sheets and practical exam (15%).

- Extraordinary written final exam (85%). A 40% minimum in the final exam is mandatory prior to add the note at the practical courses to the final mark.

In accordance with the regulations of the UPV/EHU, not taking the final evaluation test, whether ordinary or extraordinary, will mean the resignation of the call for evaluation and the qualification of the student will be recorded as a “No Show”.

The use of the book "Structure Determination of Organic Compounds. M. Badertscher, P. Bühlmann, E. Pretsch, Springer Berlin, Heidelberg 2009, ISBN: 978-3-540-93810-1, DOI: https://doi.org/10.1007/978-3-540-93810-1" is mandatory

Basic bibliography

1.- Structure Determination of Organic Compounds. M. Badertscher, P. Bühlmann, E. Pretsch, Springer Berlin, Heidelberg 2009, ISBN: 978-3-540-93810-1, DOI: https://doi.org/10.1007/978-3-540-93810-1

2.- Métodos espectroscópicos en Química Orgánica. M. Hesse, H. Meier, B. Zeeh. Ed.Sintesis. 1997

3.- Spectroscopic Methods in Organic Chemistry. D.H.Williams, I.Fleming. Ed. Mc .Graw Hill.1995

4.- Análisis orgánico. A. García, E. Teso. UNED. 1992

In-depth bibliography

- Infrared Spectroscopy: Fundamentals and Applications, B. H. Stuart, Ed Wiley , 2004
- Near Infrared Spectroscopy in Food Science and Technology .Yukihiro Ozaki, Alfred A. Christy, W. Fred Mc Clure, Ed Jhon Willey, 2006
- Course Notes on the Interpretation of Infrared and Raman Spectra. D. W.Mayo, F. A. Miller, R. W. Hannah, 2004
- Mass Spectrometry: Principles and Applications, 2nd Edition,Edmond De Hoffmann, Vincent Stroobant Ed Wiley, 2001
- Quantitative Applications of Mass Spectrometry, P. Traldi, F. Magno, I. Lavagnini, R. Seraglia, Ed Wiley, 2006
- Mass Spectra of Volatiles in Food (SpecData), 2nd Edition . Central Institute of Nutrition and Food Research Software, 2003.
- Magnetic Resonance in Chemistry and Medicine. R. Freeman.Ed.Oxford.2003
- High-Resolution NMR Techniques in Organic Chemistry. T. D.W. Claridge. Ed. Pergamon 1999
- 200 and More NMR Experiments S. Berger, S. Braun, Ed. Wiley-VCH. 2004
- Understanding NMR Spectroscopy. J. Keeler , Ed. Wiley . 2005.
- UNMR Spectroscopy in Drug Development and Analysis. U. Holzgrabe, I. Wawer, B. Diehl
- Two-Dimensional NMR Spectroscopy: Applications for Chemists and Biochemists, Second Edition, Fully Updated and Expanded to Include Multidimensional Work W. R. Croasmun (Editor), R. M. K. Carlson (Editor) 1994
- Wiley 1HNMR Spectra of Organic Compounds 2005 A. Yarkov .Software, 2006

Journals

The Journal of Organic Chemistry: http://pubs.acs.org/journal/joceah
Chemical Reviews: http://pubs.acs.org/journal/chreay
Jounal of the American Chemical Society: http://pubs.acs.org/journal/jacsat
Organic Letters: http://pubs.acs.org/journal/orlef7
Tetrahedron: http://www.sciencedirect.com/science/journal/00404020
Tetrahedron Letters: http://www.sciencedirect.com/science/journal/00404039
Journal of Heterocyclic Chemistry: http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291943-5193
Heterocycles: http://www.heterocycles.jp/index.php

Web addresses

Exercices on spectroscopy:

Elucidación de estructuras orgánicas ( Notre Dame) http://www.nd.edu/~smithgrp/structure/workbook.html
Problemas de RMN e IR ( UCLA) http://www.chem.ucla.edu/~webspectra/
Problemas IR ( Colby College) http://www.colby.edu/chemistry/JCAMP/IRHelperNS.html
PÁGINAS WEB:
Tutorial espectrometría de masas (University of Arizona) http://www.chem.arizona.edu/massspec/
Métodos modernos de espectrometría de masas (University of Leeds) http://www.astbury.leeds.ac.uk/facil/MStut/mstutorial.htm
Tutorial de RMN y problemas de espectroscopía (Imperial College) http://www.ch.ic.ac.uk/local/nmr/
Espectroscopía RMN. Libro de texto virtual ( Joseph Hornak, Rochester Institute of Technology) http://www.cis.rit.edu/htbooks/nmr/
NMR meets Musicians (University of Erlangen-Nuremberg, Institute of Organic Chemistry) http://www.chemie.uni-erlangen.de/oc/research/NMR/music.html
Herramientas espectroscópicas (RMN, IR y MS, University of Potsdam) http://www.chem.uni-potsdam.de/tools/index.html
Más herramientas espectroscópicas (Aplicaciones para la interpretación de espectros RMN, IR y MS, Colby College) http://www.colby.edu/chemistry/NMR/NMR.html