Learning objectives
ORGANIC CHEMISTRY OF BIOMOLECULES
At the end of the course, the student is expected
- to know and understand properties and reactivity-properties correlation of biologically relevant organic molecules such as carbohydrates, amino acids and peptides, nucleic acids, lipids, their mimics; to know and understand methods for their chemical modification; to know the correct representation of the molecules object of the course and the reaction mechanisms of their transformations (Knowledge and understanding).
- To be able to exploit the acquired theoretical knowledge to propose proper synthetic strategies for the achievement of complex molecules, foreseeing properties and also suggesting their possible application in different fields of science and technology; to be able to plan and design the synthetic strategies critically considering potentiality, limits and difficulties correlated with these classes of compounds; to be able to find and exploit bibliographic sources useful to reach these aims; to be able of correctly representing molecular structures and reaction mechanisms (Applying knowledge and understanding).
- To be able to evaluate problems of design related with synthesis procedures and applications of these classes of molecules; to understand and critically evaluate the literature data relative to these classes of compounds; to express personal and autonomous evaluation and consideration on the application and use of these compounds in technological, medical and biological contexts (Making judgements).
- To be able to correctly use the structural representation of the used chemical compounds; to be able to describe with correct scientific language his/her own knowledge and the proposed strategies; to be able to discuss with researchers having a scientific background in different areas such as biology, biochemistry, biotechnology having well clear the role of these classes of compounds in those scientific contexts (Communication skills).
- To have the knowledge to autonomously continue the study on the classes of compounds object of the course, being able to tackle new interdisciplinary issues related with the classes of compounds studied in the course, also with the support of information present in the literature, databases, web (Learning skills).
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
Knowledge and understanding
The aim of the course is to provide students with a thorough knowledge of the most common advanced 1D and 2D NMR techniques for structural analysis or organic compounds. In particular, at the end of the course the student will be able to:
• autonomously identifying the structure of organic compounds by interpreting a series of 1D and 2D NMR spectra;
• use scientific instruments to elaborate experimental data, to execute the analysis and the characterization of real samples;
• use computational methods for data processing.
• plan and complete an experiment through individual and /or group activities.
• autonomously collect experimental data and design the experimental activities;
• critically evaluate the experimental results;
• evaluate the quality parameters of alternative analytical techniques according to the nature of the experimental problem, as well as the possibilities and limits of more advanced analytical and characterization techniques by tackling and solving complex problems related to them.
• sustain a contradictory on the basis of opinions developed independently on issues related to their studies and make team-working in multidisciplinary projects.
• autonomously learn new scientific topics.
• autonomously tackle on new professional problems;
• autonomously study new solutions to complex problems, including interdisciplinary ones.
Prerequisites
Organic Chemistry 1 and 2
Course unit content
ORGANIC CHEMISTRY OF BIOMOLECULES
Chemico-physical properties and reactivity of carbohydrates, amino acid and peptides, lipids and nucleic acids.
Modification of their structure and synthesis of corresponding oligomers.
Artificial mimics, properties and synthesis.
Use as raw material for the production of chemicals.
Noncovalent interaction with molecular and macromolecular species.
Applications.
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
Magnetic properties of nuclei: angular momentum and spin angular momentum.
The Vector model.
Fundamental concepts of 2D NMR spectroscopy.
Relaxation processes.
The Chemical exchange.
The modern NMR spectrometer.
Interpretation of 1D e 2D NMR spectra and determination of the structure of an organic compound.
Laboratory part: use of the NMR spectrometer and recording of several 1D (1H and 13C) and 2D (COSY and HSCQ) NMR spectra of organic compounds.
Full programme
ORGANIC CHEMISTRY OF BIOMOLECULES
Amino acids and peptides
Why to synthesize a peptide. Structure and properties of amino acids and peptides. Nitrogen protecting groups: insertion and removal. Possible secondary reactions. Protecting groups of carboxylic and hydroxyl groups. Methods for activation and coupling. Possible racemisation phenomena and mechanisms. Methods of solid phase synthesis. Resins and cleavage conditions.
Carbohydrates
Role of carbohydrates in non metabolic biological processes. Structure, properties, nomenclature. Anomeric effect. Oxidation and reduction reactions. Glycosylation reactions: concept of glycosyl donor and glycosyl acceptor, promoters, protecting groups. Enzymatic synthesis of glycosidic bond. Oligosaccharide and glycoconjugates synthesis on solid phase. Synthesis of glycosidic clusters and concept of multivalency and glycoside cluster effect. Carbohydrates as renewable raw material for fine chemicals.
Nucleic acids
Structure and properties. Synthesis. Modified nucleic acids and mimics. Antigene and antisense strategies. DNA and RNA binders. Nucleic acids as smart material for nanotechnology
Lipids
Structure and properties. Autooxidation reactions. Synthesis of complex lipids: some examples. Self-assembly of lipids: double layers, lamellar phases, vesicles, liposomes. Delivery applications. Determination of size and zeta potential by DLS. Investigation through AFM and TEM
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
• Magnetic properties of nuclei: angular momentum and spin angular momentum. Microscopic magnetism. Correlation between magnetism and spin angular momentum.
• NMR Frequencies and Chemical shift. Linewidth and lineshape. Scalar coupling. The basic NMR experiment.
• Energy levels and NMR spectra. The spectrum for one spin. The energy levels for two coupled spins.
• The Vector model. The bulk magnetization. Larmor precession. Detection. Pulses. "On resonance" pulses. The rotating frame. The basic impulse-acquisition sequence. Calibration of pulses. The Spin-Echo experiment. Pulses of various phase. "Off-resonance" effetcs and "soft" pulses. Fourier Transformation and data processing. FID representation. Peaks linewidth and lineshape. FID manipulation. Zero filling.
• The "Product Operators" formalism. Product operators for one spin. Hamiltonians for spins and delays. Equation of motion. The spin-echo experiments with the product operators formalism. Product operators for two weakly coupled spins.
• Fundamental concepts of 2D NMR spectroscopy. 2D NMR experiments with coherence transfer mediated by J-coupling. COSY and DQF-COSY: pulses sequence and spectra interpretation. Double Quantum NMR Spectroscopy. Heterocorrelated 2D NMR spectroscopy. HMQC, HSQC and HMBC experiments: pulses sequence and spectra interpretation. 2D TOCSY NMR experiment: pulses sequence and spectra interpretation.
• Relaxation and Nuclear Overhauser Effect (NOE). The origin of the nuclear relaxation phenomenon. Mechanisms of relaxation. Correlation time. Population of the states. Longitudinal relaxation of isolated spins. Dipolar longitudinal relaxation of two spins. Cross-relaxation. Relaxation due to chemical shift anisotropy.
• NOEDif, NOESY and ROESY experiments: pulses sequence and spectra interpretation
• Coherence selection: phase cycling cycle and field gradient pulses. Order of coherence. Coherence transfer pathways. Frequency discrimination and peak shape.
• The modern NMR spectrometer. Magnet and Probe, Lock Channel, Shim and homogeneity of the magnetic field. RF synthesizer, amplifier and duplexer. Receiver and Quadrature detection. Analogue to digital convertor (ADC). Limits of digitization.
• 1D NMR spectra acquisition and processing (1H and 13C).
Bibliography
ORGANIC CHEMISTRY OF BIOMOLECULES
Lecture notes by the Professor, Review articles from the literature, examples of exercises and cases of study proposed during the examination. All this material is available at the website on Elly platform from the beginning of the course. It constitutes the main support for the preparation of the exam
In dept-study texts:
For the part relative to amino acids and peptides:
- Peptidi e Peptidomimetici, V. Santagada, G. Caliendo, Piccin Nuova Libraria, 2003For the part relative to carbohydrates:
- The Sugar Code. Fundamentals of Glycosciences, Hans-Joachim Gabius Ed., 2009 Wiley -VCH Verlag, Weinheim
- Carbohydrates in Chemistry and Biology, B. Ernst, G. W. Hart, P. Sinay Eds., Vol. 1-4, 2000 Wiley -VCH Verlag, Weinheim
- Carbohydrates as Organic Raw Materials, Frieder W. Lichtenthaler Ed., VCH Weinheim, 1991
- Introduction to Glycobiology, M. E. Taylor, K. Drickamer Eds., 2006 Oxford University Press
- Carbohydrate Chemistry: State of the Art and Challenges for Drug Development. An Overview on Structure, Biological Roles, Synthetic Methods and Application as Therapeutics, Ed. Laura Cipolla, Imperial College Press, 2015.
- The Molecular and Supramolecular Chemistry of Carbohydrates, S. David Ed., 1997 Oxford University Press
For the part relative to nucleic acids:
- Bioorganic Chemistry - Nucleic Acids, Sidney M. Hecht, Ed., 1996 Oxford University Press
- Gli Oligonucleotidi Sintetici - Principi e applicazioni, CNR - Progetto Strategico Nucleotidi Antisenso, UTET Periodici- DNA Interactions with Polymers and Surfactants, R. S. Dias and B. Lindman Eds, Wiley Interscience, 2008
- DNA and RNA Binders - From small molecules to drugs, M. Demeunynck, C. Bailly and W. D. Wilson Eds., Wiley-VCH, 2003
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
Lecture notes by the Professor, examples of exercises and cases of study proposed during the examination. All this material is available at the website on Elly platform from the beginning of the course. It constitutes the main support for the preparation of the exam.
Recommended Textbooks:
• Harald Gunther - NMR Spectroscopy, Basic Principles, Concepts, and Apllication in Chemistry, 3rd edition, Wiley - VCH, 2013.
• Oliver Zerbe & Simon Jurt - Applied NMR Spectroscopy for Chemists and Life Scientists, Wiley-VCH, 2014
Suggested Readings (Theory):
• James Keller "Understanding NMR Spectroscopy", 2nd Edition, Wiley, 2010.
• Neil E. Jacobsen - NMR Data Interpretation explained, Wiley, 2016
• Antonio Randazzo - Guida pratica alla interpretazione di spettri NMR, Loghia, 2017
Suggested Readings (Lab.):
• John S. Harwood & Huaping Mo - Practical NMR Spectroscopy Laboratory Guide: Using Bruker Spectrometers, Academic Press, 2015
• Matthias Findeisen & Stefan Berger - 50 and More Essential NMR Experiments: A Detailed Guide, Wiley-VCH, 2013
Teaching methods
ORGANIC CHEMISTRY OF BIOMOLECULES
Classroom teaching and solution of problems relative to identification and synthesis of derivatives belonging to the illustrated classes of compounds. The resolution of exercizes and problems is done with the direct participation and contribution of the students.
At the beginning of each course section, the basic chemical properties of the specific class of compounds are identified with the direct contribution of the students by using their knowledge in organic chemistry. This approach is useful to verify the starting knowledge of the students in organic chemistry and allow the teacher to fill possible gaps.
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
The format of the class will be lectures of one or two hours each spread over three days per week. The lab training will be articulated in four experiments of two hours each.
Assessment methods and criteria
Upon agreement with professors, after the end of the course, the evaluation of the individual modules can also be carried out separately in the form of a partial test for each module. These partial tests can also be taken on different dates. The final grade of the course will be assigned to the student as the average of the scores obtained in the individual partial tests.
ORGANIC CHEMISTRY OF BIOMOLECULES
Oral examination based on the resolution and discussion of exercises on the reactivity and synthesis of lipids, saccharides, amino acids and peptides, nucleic acids, theri mimics.
It is verified the acquired knowledge relative to strategy of modification of amino acids, carbohydrates and nucleotides; synthetic strategy of peptides, oligosaccharides, oligonucleotides; possible application in scientific fields of these classes of molecules thanks to their ability in giving interactions with biologically and medically relevant substrates and species and thanks to their self-assembly properties.
During the examination, questions relative to each of the four course sections (lipids, saccharides, amino acids and peptides, nucleic acids) are posed to the student. It is given to the student the possibility of starting the exame with a topic of own choice.
Specifically, some relatively complex molecules, generally taken from study and research cases present in literature, are proposed to the student for the presentation of their properties and as synthetic targets. In this way the acquired ability is evaluated of planning a correct strategy of synthesis based on the methodologies shown in the course, by using protecting and activating groups, by estimating advantages and drawbacks of the various possibilities and experimental conditions, analysing problems occuring and possible solutions. During the exame, the student has to show to be able to use a correct and appropriate scientific language and the correct representation of reaction mechanisms, molecular structures and functions.
The demonstration of a basic knowledge of tghe course contents, including the main properties of the studied compounds and their reactivity, determines an evaluation of 18-21/30 points; if some of the answers are characterized by a punctual description of reactions and molecules the score reaches 21-24/30; exhaustive answers like these for all the issues discussed during the exam determine a score of 24-27/30; a deep discussion of the topics, even evidencing the ability of the student in tackling new problems and targets, together with the ability of pointing out problems and applications of the compounds under investigation, determines a score of 27-30/30. Definitely exhaustive answers and discussion, with the use of a proper language together with a rigorous representation of molecules and reaction mechanims bring to “laude”.
PHYSICAL METHODS IN ORGANIC CHEMISTRY AND LABORATORY
The final examination will include a written part in which the candidates have to assign the structure of a known organic compounds to the resonances of several 1D and 2D NMR spectra (MAX. 21/30). In the following oral part, the candidates will be enquired on the theoretical topics discussed during the first part of the course (MAX. 9/30).
The demonstration of a basic knowledge of the contents of the course, which includes the ability to assign the resonances of 1D and 2D NMR spectra to the structure of an organic compound, determines a score of 18-21/30. A precise description of the instrumental and experimental aspects of the NMR technique determines a score of 21-24/30. A comprehensive and in-depth discussion of the theoretical aspects of the NMR spectroscopy with answers given using an appropriate language will be awarded with a score of 27-30/30. The ability of the candidate to face new problems together with the identification of possible problems and applications determines the assignment of an evaluation with honors.
Other information
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