MEDCHEM.01

Introduction to Chirality

Stereochemistry and Chirality

  • Importance: Drug design, action, and enzyme catalyzed reactions.

  • Chiral amino acids are foundational for enzymes and proteins, making all enzymes and proteins chiral.

Summary of Isomerism

Classification of Isomers

  • Isomers: Same molecular formula, different bond patterns.

  • Constitutional/Structural Isomers: Example C2H6O (alcohol/ether).

  • Stereoisomers: Same molecular formula but differ in 3D spatial arrangement.

    • Conformational Isomers: Different by rotations about single bonds.

    • Configurational Isomers: Not achievable by simple rotations.

Chirality

  • Chiral molecules cannot be superimposed on their mirror images (like left and right hands).

  • Achiral molecules can be superimposed on their mirror images.

  • Example: a chair is achiral; hand-like shapes are chiral.

Optical Isomers

  • The mirror image of a chiral molecule is a non-superimposable enantiomer.

  • Enantiomers are chemically identical but have unique 3D shapes; they exhibit different biological properties, especially in drug-receptor interactions.

When Do Molecules Become Chiral?

  • A carbon with four different groups is a stereogenic center, leading to two enantiomers.

  • Configuration differs between enantiomers; chiral molecules lack a plane of symmetry.

  • Carbon adopts tetrahedral geometry.

Non-superimposable Mirror Images

  • Enantiomers have distinct 3D arrangements due to unique substituents on carbon.

Importance of Chirality in Nature

  • Example: A drug with two enantiomers can interact selectively with a chiral enzyme; one enantiomer may be ineffective, leading to side effects.

Chiral Carbons

  • Tetrahedral carbon must have four different substituents to be considered chiral.

  • Its mirror image is an enantiomer.

Chirality Examples

  • 2-Chloropropane: Not chiral due to a plane of symmetry.

  • 3-Methylpentane: Not chiral; identical after rotation.

  • 3-Methylhexane: Chiral with distinct enantiomers even after rotation.

Generalization of Chirality

  • Carbon with four distinct groups forms a chiral molecule (chirality center).

  • Achiral versus chiral classifications should be understood.

Enantiomers

  • Non-superimposable mirror images with identical physical properties (melting point, boiling point).

  • Each enantiomer rotates plane-polarized light in opposite directions; chiral molecules are optically active.

Plane-polarized Light

  • Enantiomers rotate light equally but in opposite directions.

  • Terms: d (dextrorotatory, clockwise) and l (levorotatory, counterclockwise).

Racemic Mixture

  • A 50:50 mix of two enantiomers is termed racemic. It is optically inactive due to light cancellation effects.

Example - Enantiomers of Lactic Acid

  • (+) Lactic Acid: Melting point = 53 °C; [α]25 = +3.33.

  • (-) Lactic Acid: Melting point = 53 °C; [α]25 = -3.33.

Racemic Mixture of Lactic Acid

  • A mixture of both enantiomers; optically inactive due to equal contributions from both forms.

Specific Rotation Measurements

  • Formula: [α] = α (observed rotation) / (concentration x path-length).

  • Observations affected by various factors like temperature and light wavelength.

  • Typical wavelength used is 589 nm from sodium lamps.

Specific Rotation Calculation Examples

  • Sample calculations for optical rotation based on given masses, concentrations, and observed rotations.

Summary of Key Concepts

  • Achiral molecules: Superimposable on their mirror images; optically inactive.

  • Chiral molecules: Non-superimposable; optically active; feature tetrahedral carbons with four distinct groups.

  • Enantiomers: Stereoisomers; non-superimposable mirror images.

  • Racemic mixture: An equal mix of enantiomers leading to optical inactivity.