MEDCHEM_01_2425

Stereochemistry and Chirality

• Importance:

  • Critical in drug design and enzyme-catalyzed reactions.

  • Enzymes and amino acids are chiral, affecting their function.

Summary of Isomerism from Semester 1

• Rotamers: A type of stereoisomer that can interconvert by bond rotation.

• Non-rotamer stereoisomers cannot convert without breaking bonds.

Understanding Chirality

• Chiral Molecules: Cannot be superimposed on their mirror image.

• Achiral Molecules: Can be superimposed on their mirror image (e.g., chair structure).

• Example: Hands as models of chirality - right glove vs. left glove.

Optical Isomers: Chirality and Enantiomers

• Chiral molecules have unique 3D shapes; they are non-superimposable mirror images called enantiomers.

• Although chemically identical, enantiomers exhibit different biological properties, especially in drug interactions with enzymes/receptors.

Conditions for Chirality

• Stereogenic Centre: Carbon atom with four different groups attached.

• Configuration: Arrangement of groups around the carbon.

• Chirality: Molecules must not have a plane of symmetry to be considered chiral.

Examples of Chiral and Achiral Molecules

• 2-Chloropropane: Achiral due to symmetry.

• 3-Methylpentane: Achiral, can be transformed into overlapping structure by rotations.

• 3-Methylhexane: Chiral; its mirror images are distinct and cannot be superimposed.

Generalization of Chirality

• Compounds with four different groups around carbon create a chiral molecule.

• Chirality Center: The specific carbon atom making a molecule chiral.

Characteristics of Enantiomers

• Definition: Non-superimposable mirror images.

• Identical PHYSICAL properties (e.g., melting point, boiling point, density).

• Rotate polarized light in opposite directions (optically active).

Plane-Polarized Light and Enantiomers

• Enantiomers rotate the plane of polarized light equally, but in opposite directions:

  • Dextrorotatory (d- or +): clockwise rotation

  • Levorotatory (l- or -): counterclockwise rotation

• A racemic mixture contains equal amounts of both enantiomers and is optically inactive.

Case Studies in Enantiomers: Lactic Acid

• Lactic acid:

  • (+)-lactic acid: melting point 53°C, rotation +3.33

  • (-)-lactic acid: melting point 53°C, rotation -3.33

Racemic Mixture Characteristics

• Racemic mixtures consist of 50:50 proportions of enantiomers, resulting in no net optical rotation.

Calculation of Specific Rotation

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

• Factors affecting specific rotation include temperature, concentration, and wavelength of light used in measurement.

Summary of Key Concepts

• Achiral molecules: can be superimposed; optically inactive.

• Chiral molecules: cannot be superimposed; optically active.

• Tetrahedral carbon with four distinct groups: generates chiral molecules.

• Enantiomers: non-superimposable mirror images that exhibit optical activity.

• Racemic mixture: optically inactive by having equal proportions of enantiomers.

Contact Information

• For more information, contact Dr. Declan Gaynor via email: dgaynor@rcsi-mub.com.