Introduction to Organic Chemistry and Stereochemistry

Course Overview

Course Title

Medical Chemistry: Introduction to Organic Chemistry and Stereochemistry of Organic Compounds

Instructor

Ilias Mylonis

Date

20/10/2025

Course Contents

  • Distribution of electron cloud in molecules:
    • Inductive (I) and conjugate (delocalization) (R) effects
    • Resonance
  • Classification of reactions and reagents in organic chemistry:
    • Nucleophilic and electrophilic reagents
    • Free radicals
  • Functional groups of organic compounds and their role in the design of new drugs
  • Stereochemistry and stereoisomerism:
    • Mirror image isomers / enantiomers
    • Chiral and achiral compounds
    • Asymmetric (chiral) center
    • Optical activity: (+) – right-handed and (−) – left-handed enantiomers
    • Racemic mixture and racemization
    • Fischer projection
    • Absolute stereochemical structure: D, L symbolism
    • Stereoisomerism of chiral centers according to the CHAN-INGOLD-PRELOG rules and R-S symbolism
    • Diastereomerism, meso-isoform
    • Geometric isomerism: CIS - TRANS, Z-E, priority of ligands

Key Concepts in Organic Chemistry

Carbon-Containing Molecules

  • Organic Chemistry is mainly concerned with carbon-containing substances, except for certain inorganic compounds such as CO, CO₂, and carbonates.

Carbon Valency and Geometry

  • Carbon can form four covalent bonds, leading to various molecular geometries:
    • Tetrahedral (109.5°)
    • Trigonal (120°)
    • Linear (180°)

Carbon Chemistry - Functional Groups

Overview
  • Acknowledge the diversity and variation among organic compounds through their functional groups.
Common Functional Groups
  • Alcohols, Aldehydes, Ketones, Carboxylic Acids, Amines, etc.

Properties and Reactions of Organic Compounds

Factors Affecting Properties

  1. Distribution of electron cloud in molecules:

    • Inductive (I) Effect:

      • A sequential polarization of σ-bonds in a molecule caused by neighboring electronegative or electropositive groups.
      • This polarization creates polar molecules with dipole moments.

    • Conjugate (Delocalization) (R) Effect:

      • Occurs when π-orbital electrons are delocalized across alternating single and multiple bond systems, thus stabilizing the molecule.
Resonance
  • In resonance structures, the lateral overlap of p-orbitals leads to an extended π-electron density across a larger area, resulting in lower energy and increased stability.
Inductive Effect and Organic Acids
  • The strength of organic acids is affected by the inductive effect of surrounding ligands.

Reaction Classifications in Organic Chemistry

Reagents

Nucleophilic Reagents
  • Defined as species that donate a pair of electrons to form bonds.
Electrophilic Reagents
  • Defined as species that accept or share a pair of electrons to form bonds.
Free Radicals
  • Any molecular species capable of independent existence containing an unpaired electron, making them highly reactive and involved in initiating chain reactions.

Stereochemistry

Spatial Arrangement of Atoms

Stereoisomerism
  • Defined as compounds exhibiting the same molecular and structural formula with differing spatial arrangements.

  1. Geometric Isomerism:

    • Occurs due to fixed double bonds that inhibit free rotation, leading to isomers such as cis and trans or E and Z.

  2. Optical Isomerism:

    • Enantiomers are chiral compounds which are mirror images of each other and are not superimposable.

Characteristics of Chiral Compounds

  1. Contains at least one carbon atom bonded to four different groups.
  2. Exhibits optical activity by rotating the polarization of plane-polarized light.
  3. Demonstrates different biological and pharmacological activities based on chirality (e.g., D-Glucose versus L-Glucose).

Optical Activity

  • One enantiomer rotates polarized light clockwise (+, dextro) while the other rotates it counter-clockwise (−, levo).

Stereochemical Structures

Fischer Projection

  • A two-dimensional representation used to depict the absolute stereochemistry of a molecule, based on glyceraldehyde as a standard.
  • Key Features:
    • Horizontal bonds project forward (towards the viewer), while vertical bonds project backward (away from the viewer).

D-, L- Isomers

  • Relate to the configuration established by Fischer projections; different from the optical activity indication (+) and (−). Reactions that do not affect the asymmetric carbon do not alter D-, L- configurations but can change optical activity.

Stereoselectivity in Drug Activity

  • Specific enantiomers of drugs have distinct pharmacological effects, exemplified by ibuprofen, where only the S- form is active and the R- form is inactive.
  • Enzymes often display stereoselectivity, selectively metabolizing certain enantiomers, leading to the production of only one chiral isomer from symmetrical substrates.

Summary of Key Points

  • Understanding of inductive and conjugate effects is crucial.
  • Familiarity with classifications of reagents is essential for grasping organic reactions.
  • Mastery of stereochemistry, including enantiomers, diastereomers, and geometric isomers, is vital in the context of drug design and biological applications.