Chirality and Enantiomers

Chirality Introduction

• Chirality is the focus, building upon lab work.
• Two lectures are interconnected.

Thalidomide Story

• Thalidomide had two enantiomers (isomers).
• Given as a leprosy medicine without separating enantiomers.
• One enantiomer was effective against leprosy.
• The other enantiomer caused birth defects (teratogenic).
• Led to the requirement for chirally pure drugs.

Carvone Example

• Carvone enantiomers: spearmint vs. caraway oil.
• Same by standard tests, different smells due to nose's differential response.

Isomers

• Diastereomers (non-mirror image stereo isomers) vs. Enantiomers (mirror images).
• Cis/trans isomers are diastereomers.

Chiral Centers

• Carbon atom with four different substituents: a chiral center.
• Mirror image of a chiral molecule is not superimposable.
• Analogous to left and right hands.

Chirality in Biology

• Proteins are made of 20 amino acids.
• Valine example: amine, carboxylic acid, CH_3 group, and H (pointing away).
• Central carbon in valine is a chiral center.
• Mirror image of valine is a different molecule.

L-Amino Acids

• Proteins in nature are made of L-amino acids.
• Synthesizing chirally pure compounds is challenging.
• Origin of exclusive use of L-amino acids in nature is unknown.
• D-amino acids yield proteins with different functions.
• Glucose is also a single enantiomer in nature.

Terminology

• Achiral: molecule without a chiral center.
• Chiral: molecule with a chiral center.
• Racemic mixture: 50/50 mix of enantiomers.

Chirality in Everyday Life

• Pasta, hands, feet, shells, pharmaceuticals.
• Pharmaceuticals often chiral due to protein chirality.
• Enantiomers can have different effects: painkiller vs. anti-cough, sedative vs. mutagen, bitter vs. sweet.

Enzyme Interactions

• Enzymes have lock-and-key relationships with molecules.
• Only one enantiomer fits the enzyme surface correctly.

Identifying Chiral Centers

• Skill: Identify carbons with four different substituents.
• Examples provided with explanations of chiral vs. achiral centers.
• If a carbon has a double bond or two identical substituents it cannot be chiral.
• Symmetry within a molecule can negate chirality.

Optical Activity Demonstration

• Chirally pure compounds are optically active; rotate light.
• Sucrose (table sugar) is used as an example.

Sucrose and Light Rotation

• Linearly polarized light is shone through sucrose solution.
• Sucrose rotates the plane of light, separating colors.
• Each color rotates at a different rate (blue > red), creating a rainbow effect.

Drawing Conventions for Chiral Centers

• sp3 (tetrahedral) carbon has four bonds; two in the plane, one forward (wedge), one back (dashed).
• 2-butanol example with different drawing styles.

Naming Enantiomers: R/S System

• R/S system is universally applied.
• Locate stereo center, assign priorities to substituents (higher molecular weight = higher priority).
• Orient molecule with lowest priority group pointing away.
• Read remaining groups: clockwise = R (right-handed), anticlockwise = S (sinister).
• Cahn-Ingold-Prelog rules for priority assignment.

Example: Bromochloromethane

• Bromine > Chlorine > CH_3 > H.
• Anticlockwise arrangement: S enantiomer.

Further Examples

• Identifying priority: CH2OH beats CH2CH3 (O > C).
• Carbon double-bonded to carbon beats carbon single-bonded to carbon.

Amino Acid Example: Serine

• Serine: NH2, CO2H, CH_2OH.
• Nitrogen > Carbon double-bonded to oxygen > CH_2OH > H.
• Recognizing and drawing amino acids is important.

Philosophical Questions

• 20 canonical amino acids constitute all of biology.

Additional Notes

• Illustrations of molecules that help determine the spatial orientation of substituents.
• One can redraw molecules to visualize substituents in different planes.
• It is useful have a model kit to physically visualise the molecules in three dimensions.
• Additional questions on chiral center determination and R/S center determination presented for the audience.