c.i. PROGETTAZIONE MOLECOLARE E CHIMICA INORGANICA SUPRAMOLECOLARE

Academic Year 2021/2022 - 1° Year - Curriculum Chimica Organica e Bioorganica

Learning Objectives

• PROGETTAZIONE MOLECOLARE

  The course will show the relevance of chemioinformatics in chemical research. Although chemioinformatics methods are mainly applied in the chemical-pharmaceutical field, the student will be sensitized to the possibility of applying such methodologies to various fields of chemistry.
  The course should allow the student to acquire the following basic knowledge:
  Know the definition of chemioinformatics and its historical evolution;
  Understand the importance of chemioinformatics in various chemical research fields, with particular attention to drug discovery procedures.
  Know the economic aspects of chemioinformatics, which allows to reduce the cost of the survey.
  Know the basics of chemioinformatics.
  Know the basics of drug metabolism and the methods associated with that research field.
  Know chemioinformatics methodologies to be applied to the study of drug human metabolism.

  This course aims at providing the concepts for the application of the physical organic chemistry to drug discovery. In particular, the main physical chemical and ADME properties of drugs or potential drugs will be discussed, to learn how to modulate them through the modulation of their chemical structure.
  
  Main knowledge acquired will be:
  
  1) Basic concepts of the drug discovery and drug development processes
  
  2) Knowledge of the main aspects of absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs
  
  3) Knowledge of experimental and in silico methods for the determination of acid-base properties, lipophilicity, permeability and solubility
  
  4) Knowledge of the main chemical strategies for ADME optimization
  
  5) Knowledge of methods for structure-activity relationship studies
  
  Understand the basic principles of designing drugs and classical methods associated with this field of research.
  Know chemioinformatics methodologies to be applied to drug design.

  To acquire experience on the methodologies and techniques of organic synthesis through the preparation of some products and their structural determination. With reference to the Dublin Descriptors, this course aims to transfer the following transversal skills to the student:

  Knowledge and understanding: Inductive and deductive reasoning skills;

  Ability to rationalize and predict the reactivity of organic molecules;

  Ability to apply knowledge:

  Ability to design a synthetic path suitable for obtaining a precise organic molecule;

  Ability to foresee the necessary instrumentation for the realization of the synthesis;

  Ability to identify the optimal reaction conditions for a given reaction.

  Autonomy of judgment: Critical reasoning skills;

  Self-assessment of learning through interactions in the classroom with colleagues and with the teacher.

  Communication skills: Ability to describe in oral and written form, with properties of language and terminological rigor, one of the topics covered, using both power point presentations and the blackboard

• CHIMICA INORGANICA SUPRAMOLECOLARE

  Specific educational goals of this course are: knowledge of the first principles (forces, interactions and processes) at the basis of non-covalent chemistry. With the gaze turned to natural systems, we want to lead the student to the understanding of self-assembly phenomena to allow the design of supramolecular devices. To this end, an overview of the rationale behind supramolecular design will also be presented: that is, the scientific works based on the logical processes that allow to proceed from design to the non-covalent synthesis of supramolecular species with the wanted structure and specific chemical-physical properties. To this end, the relevance of hierarchical processes will be illustrated and how to exploit the thermodynamic-kinetic dichotomy. The role of metal ions in determining the characteristics of the aggregates will be highlighted throughout the program.

  Furthermore, with reference to the so-called Dublin Descriptors, this course contributes to acquiring the following transversal skills:

  Knowledge and understanding: Knowledge of hierarchical processes and of the thermodynamic-kinetic dichotomy, knowledge and understanding of the role of conformations in modulating the properties of polymers.

  Applied knowledge and understanding: Ability to apply the knowledge described above through the examples shown in class, both in textbooks and in published research.

  Autonomy of judgment: Students learn to objectively evaluate what they have learned during lessons through interaction with the teacher and the different examples of application of logical-deductive tools in design.

  Communication skills: Ability to describe in oral form, with properties of language and terminological rigor, the scientific topics presented in class, illustrating the logical path that starting from the motivations leads to the results.

  Learning skills: Learning skills are assessed through discussions during the lessons - which are an important part of the course - and the oral exam.

Course Structure

• PROGETTAZIONE MOLECOLARE

  The teaching will take place through the discussion of the various topics reported in the program and will include days dedicated to the clarification of doubts and the simulation of the oral exam.

• CHIMICA INORGANICA SUPRAMOLECOLARE

  This course mainly consists of class lectures.

Detailed Course Content

• PROGETTAZIONE MOLECOLARE

  Chemometrics concepts
  Molecular representation (graphs, fingerprints, MIF) and
  molecular minimitation.
  Advanced molecular descriptors. QSAR and 3D-QSAR.
  Circular molecular descriptors: the Moka method.
  3D molecular descriptors: the VolSurf method.
  Applications of the VolSurf method in the field of ADME
  Calculation methods of bitstrings and fingerprints. Methods of calculating molecular similarity.
  The Flap method for the calculation of molecular similarity.
  The Flap method for the calculation of affinity with macromolecules.
  Computational methods for metabolism prediction. The MetaSite method.

  Computer exercises

• CHIMICA INORGANICA SUPRAMOLECOLARE

  Introduction to supramolecular chemistry: the fundamentals of non-covalent synthesis

  Nature as a Model: learning as to read molecular and supramolecular information (DNA, proteins). Relationships between structures (primary, secondary, tertiary) and function. Allosteric effect. Hierarchy of self-assembling and kinetic inertia: thermodynamics and kinetics at work

  -Nature of non-covalent interactions. The role of solvent: solubility and solvofobicity.

  -Classification of synthetic supramolecular compounds. Chelation effect and macrocycle effect. Organization and complementarity.

  Non-covalent synthesis and covalent synthesis: a marriage of convenience

  Host-guest chemist

  -Anion Receptors. Cation Receptors. Neutral molecule receptors.

  Self-assembly

  - Supramolecular architectures, ideas of crystal engineering.

  - Supramolecular stereochemistry. Intrinsic chirality and induced chirality. Chiral memory.

  -Catalysis and supramolecular reactivity. Self-replication.

  Supramolecular at Work: Nanotechnologies.

  Nanomedicine.

  -Imaging (MRI, luminescent probes, radiolabeling), radiotherapeutic compounds

  Sensors

  - Selective ionic electrodes (ISEs), iono-selective membranes, chromo ionophore, piezoelectric and fluorescence sensors, electronic nose

  Supramolecular switches.

  - Optical and hybrid switches.

  -Logic gates (YES, NOT, AND, OR, XOR) from supramolecular systems.

  Future Applications: nanomacchine

  - Top-down and bottom-up strategies for building nanostructures.

  - Molecular machines in the biological world. Artificial molecular machines.

Textbook Information

• PROGETTAZIONE MOLECOLARE

  handouts provided by the teacher

• CHIMICA INORGANICA SUPRAMOLECOLARE

  Notes from classes

  • J.-M. Lehn, Supramolecular Chemistry, VCH
  • J. W. Steed and J. L. Atwood, Supramolecular Chemistry, Wiley
  • P. D. Beer, P. A. Gale and D. K. Smith Supramolecular Chemistry,OCP