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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.