ADVANCED ORGANIC CHEMISTRY

The course aims to deepen the understanding of organic reaction mechanisms, non-covalent interactions, and the principles of supramolecular chemistry. Students will develop advanced skills in predicting molecular reactivity, designing supramolecular systems, and performing kinetic characterization of reactions. The study of catalysis—both organic and enzymatic—will also be addressed, with a focus on energetic and mechanistic aspects.

Dublin Descriptors

• Knowledge and understanding
Students will acquire advanced and in-depth knowledge of organic reactions, supramolecular chemistry principles, non-covalent interactions, and chemical kinetics. They will be able to comprehend and interpret scientific literature in the field of modern organic chemistry and molecular materials.

• Applying knowledge and understanding
Students will be able to apply theoretical concepts to solve complex chemical problems, such as designing supramolecular systems, predicting molecular reactivity, and analyzing reaction kinetics. They will also be capable of using spectroscopic and calorimetric techniques to characterize molecular interactions.

• Making judgements
The course develops the student’s critical ability to analyze experimental data, evaluate alternative mechanisms, and interpret complex phenomena related to chemical reactivity and supramolecular structure formation. Students will be able to formulate hypotheses and propose experimental strategies to test them.

• Communication skills
Students will be able to clearly and effectively communicate complex topics in advanced organic chemistry, using correct scientific terminology both in written form (reports, articles) and orally (presentations, scientific discussions), including in interdisciplinary and international contexts.

• Learning skills
The course provides methodological tools to support autonomous learning and continuous scientific development, equipping students with the skills needed for research activities (e.g., doctoral studies) or professional work in advanced chemical innovation and development

At the end of the course, the student will be able to:
• Analyze and interpret complex organic reaction mechanisms
• Describe and apply the principles of supramolecular chemistry
• Design molecular systems based on non-covalent interactions
• Interpret kinetic and thermodynamic data
• Understand the function and mechanisms of enzymatic catalysis

Information for students with disabilities and/or SLD
To guarantee equal opportunities and in compliance with the laws in force, interested students can ask for a personal interview in order to plan any compensatory and/or dispensatory measures, based on the didactic objectives and specific needs.

Basic knowledge of:

• Organic chemistry (additions, eliminations, substitutions, reaction mechanisms)
• Physical chemistry (thermodynamics and kinetics)
• Basic spectroscopy (UV-Vis, NMR)

Course Content

1. Binding Forces and Molecular Recognition

• Ionic, dipolar, hydrogen, halogen, and π-π interactions
• Hydrophobic effect and its implications
• Theoretical models (e.g., Born equation)
• Concepts of complementarity and preorganization

2. Supramolecular Chemistry

• General principles: non-covalent forces, self-assembly
• Synthetic receptors: crown ethers, cryptands, cyclodextrins, carcerands, calixarenes
• Complex architectures: catenanes, rotaxanes, pseudorotaxanes, molecular capsules
• Covalent reversible and non-covalent synthetic methodologies
• Structural characterization in solution: NMR (DOSY, ROESY), DLS, GPC
• Applications: optoelectronic materials, supramolecular polymers, photonic devices

3. Reactivity, Kinetics, and Mechanisms

• Energy surfaces, reaction coordinates
• Transition State Theory (TST)
• Advanced kinetic principles: Hammond postulate, Curtin-Hammett principle, microscopic reversibility
• Complex kinetics and steady-state approximation
• Experimental techniques: flash photolysis, flow methods, pulse radiolysis
• Marcus theory and More O’Ferrall–Jencks diagrams

4. Catalysis and Enzymatic Catalysis

• Types of catalysis: acid-base, nucleophilic, metal-catalyzed, intramolecular
• Enzymatic catalysis: examples and mechanisms, Michaelis-Menten equation
• Reversible and irreversible inhibition
• Artificial and biomimetic enzymes

5. Advanced Organic Reaction Mechanisms

• Electrophilic and nucleophilic additions to double bonds and carbonyls
• Eliminations, epoxidation, hydration

• Clayden, Greeves, Warren, Wothers – Organic Chemistry
• Lehn, J.-M. – Supramolecular Chemistry
• Anslyn & Dougherty – Modern Physical Organic Chemistry
• Dispense e articoli forniti dal docente

For the assignment of the final grade, the following criteria will be considered:

Grade 29–30 with honors:
The student has an in-depth knowledge of the subject, is able to promptly and accurately integrate and critically analyze the presented situations, independently solving even highly complex problems. They demonstrate excellent communication skills and command of language.

Grade 26–28:
The student has a good knowledge of the subject, is able to integrate and analyze the presented situations in a critical and coherent manner, can solve complex problems with reasonable autonomy, and presents the topics clearly using appropriate language.

Grade 22–25:
The student has a fair knowledge of the subject, though limited to the main topics. They can integrate and critically analyze the presented situations, though not always consistently, and present the content fairly clearly with a decent command of language.

Grade 18–21:
The student has the minimum required knowledge of the subject, with limited ability to integrate and critically analyze the presented situations. Their explanations are sufficiently clear, although their language proficiency is underdeveloped.

Exam not passed:
The student does not possess the minimum required knowledge of the core course content. Their ability to use specific terminology is very poor or nonexistent, and they are unable to apply the acquired knowledge independently.

1. Non-covalent interactions and molecular recognition

• What are the main non-covalent forces involved in molecular recognition? Provide examples.

• Explain the hydrophobic effect and how it influences the aggregation of organic molecules in water.

• Compare cation–π and π–π stacking interactions in terms of strength, orientation, and biological relevance.

• Describe the concept of preorganization and its importance in the design of molecular receptors.

2. Supramolecular chemistry

• Illustrate the structural and functional differences between crown ethers, cryptands, and cyclodextrins.

• Explain the concept of self-assembly and provide an example of a self-assembled supramolecular architecture.

• What is the difference between a catenane and a rotaxane? Describe a synthetic strategy for one of them.

• What experimental techniques can be used to characterize molecular capsules in solution?

3. Reactivity, kinetics, and mechanisms

• What does a potential energy surface represent? Draw a reaction coordinate diagram.

• Explain transition state theory (TST) and compare it with the Arrhenius equation.

• Describe the Hammond postulate and provide an example of its application to a reaction mechanism.

• What information can be obtained from a More O’Ferrall–Jencks diagram?

4. Catalysis and enzymatic catalysis

• Compare specific and general acid-base catalysis.

• Explain the mechanism of action of carboxypeptidase A or another enzyme covered in the course.

• How is the KM value determined, and what does it indicate in an enzymatic system?

• Describe the differences between competitive, non-competitive, and uncompetitive inhibition.

5. Advanced organic reaction mechanisms

• Describe the mechanism of electrophilic addition of HBr to an alkene.

• Illustrate the epoxidation mechanism of an alkene with m-CPBA.

• What role do electronic effects play in the reactivity of carbonyl compounds?

• Predict the major products and stereochemistry of a nucleophilic addition to an asymmetric ketone.