Week 2 BC L2

Introduction to Chirality

• Chirality: The three-dimensional orientation of molecules.

• Importance: Chirality is crucial in chemistry and biology.

• Most molecules in nature are chiral, and their interactions matter significantly.

Learning Outcomes

• Understand the concept of isomers.

• Differentiate between constitutional isomers and stereoisomers.

• Learn about the stereo center, mirror images, enantiomers, and diastereoisomers.

• Familiarize with nomenclature for stereocenters (R/S or E/Z systems).

• Explore the biological significance of chirality.

Isomers

Definition

• Isomers: Molecules with the same molecular formula but different arrangements of atoms in space .

Types of Isomers

Constitutional Isomers

• Definition: Molecules that differ in the connectivity of atoms (skeleton arrangement). - Different atom-to-atom connectivity, basically different molecules, buts same formula

• Examples include butane and isobutane, which have the same molecular formula (C4H10) but different structural formulas.

• Examples:

  • Butane (linear) vs. 2-methylpropane (branched).

  • Physical property differences (boiling points).

• Significance: Different physical properties and chemical behaviors

Stereoisomers

• Definition: Molecules with the same connectivity but different three-dimensional orientations.

• Key Example: Dimethylcyclohexane with different methyl group orientations.

• Notation:

  • Bold lines indicate bonds coming out of the plane.

  • Dotted lines indicate bonds going behind the plane.

Specific Cases of Stareoisomers

Cis-Trans Isomers (Geometric Isomers)

• Apply to only alkenes where rotation is restricted - so they will stay only on one side as cant rotate in space

• Cis: Same side orientation of substituents.

• Trans: Opposite sides orientation of substituents.

E/Z Nomenclature

• E (for 'entgegen', opposite) is for trans-like isomers.

• Z (for 'zusammen', together) is for cis-like isomers.

• Usage: Important for accurate naming of compounds with different substituents.

  Importance of Priorities

  • Used when comparing substituents on alkenes.

  • Highest atomic number gets the highest priority.

  • Example with chlorine and protons indicating their orientations in E/Z nomenclature.

  • You draw a line down the center and only compare the atomic mass of the molecules on each side (compare both on left side, then compare both on right side)

Conclusion

• Chirality and isomerism are essential in understanding molecular interactions.

• Familiarize with nomenclature as it plays a significant role in organic chemistry.

Overview of Chirality

• Chirality Definition: Refers to objects or molecules that are non-superimposable on their mirror images.

• Chiral Object Examples: Hands and feet exhibit chirality; their mirror images cannot be aligned perfectly.

• Achiral Object Definition: An object whose mirror image can be rotated and become superimposable on itself, e.g., a straight rod.

Chirality in Nature

• Widespread Occurrence: Chirality is common in nature, present in various organisms and structures, such as butterflies.

• Microscopic and Macroscopic Symmetry: Chirality is observable at both macroscopic levels (hands, wings) and at atomic levels in molecules.

Chirality in Chemistry

• Basic Molecule Example: Introduction of chirality through the structure of carbon atoms in molecules.

  • Chiral Molecule: A molecule that is non-superimposable on its mirror image. Example: A chiral carbon bonded to four different groups.

  • Achiral Molecule: If rotating a mirror image returns it to the original form, it is achiral.

  • Stability of Stereocenters: If a carbon atom connected to four different substituents exists, it is classified as a stereocenter, which likely contributes to chirality.

  • If the carbon atom in the middle has 4 substituents (groups attached to it) , then the carbon atom will be called a stareocentrum or stereogenic centre as it can use this chirality

Stereocenters

• Identification: Atoms (typically carbons) with four different substituents that create multiple configurations: original and mirror image.

• Chiral Pairs: Different structures resulting from stereocenters are known as enantiomers.

• Example: Lactic acid and its enantiomers; enantiomers show structural differences but are indistinguishable in an achiral environment.

Enantiomers vs. Achiral Molecules

• Enantiomers: Pairs of molecules that are mirror images; exhibit no differences in physical properties when in an achiral environment. Enantiomer is the direct mirror image of any molecule that possesses a chiral center, meaning that it cannot be superimposed onto the original molecule.

• Enantiomers do not differ in chemical and physical properties. The enantomers will only behave differentluy in a chiral environment ; for example, they may interact differently with other chiral substances, leading to variations in reaction rates and product formations - occurs largly in nature

• Enantomers also behave differently in polarised light, shifting to different sides

• Chiral Environment: In a chiral setting (like taste perception), enantiomers can elicit different responses.

• Taste Example: L-asparagine (bitter) versus D-asparagine (sweet); indicates that chiral environments affect perceptions significantly.

Optical Activity and Polarized Light

• Polarized Light: When directed through chiral substances, enantiomers can cause light to rotate in different directions.

• Measurement Tool: Using polarized light, the distinction between two enantiomers becomes apparent, as they rotate light by differing angles.

• The (+) and (-) referse to the optical activity of the enantomers (going to the positive or negative angle)

Identifying Chirality

• Symmetry is Key: To determine if a molecule is achiral, identify any planes of symmetry within the structure.

• Chiral vs. Achiral: A lack of internal symmetry indicates chirality, whereas a molecule demonstrating symmetry is automatically classified as achiral.

• Example of Symmetry: Bromochloromethane demonstrates a clear plane of symmetry, identifying it as achiral without further analysis of bonds and configurations.

Summary and Next Steps

• Important Concepts: Recognizing chirality is fundamental in chemistry due to its implications in molecular interactions and physical properties.

• Next Topic: The following video will focus on the naming of enantiomers and the importance of understanding chirality in other contexts.

Naming Enantiomers

• Enantiomers: Molecules that are mirror images of each other.

• Lactic acid example: Understanding how to name its enantiomers.

• Measurement challenge: Measuring enantiomers can be complex and not practical with simple drawings, leading to the need for a systematic approach.

Cahn-Ingold-Prelog System of Nomenclature

• CIP Rules: A nomenclature system for naming enantiomers developed by Cahn, Ingold, and Prelog.

• Labels: Each enantiomer is labeled as either R (rectus) for right or S (sinister) for left.

• St stereogenic center: Identify the stereogenic center denoted with a star (*) on the molecule, which indicates that the molecule can exist in R or S forms.

Assigning Priorities

• Identifying substituents: Assign priority based on atomic number connected to the stereocenter. Don’t worry about the atomic mass of the whole molecule, only the one connected to the stereocenter

• Order of priorities:

  1. Highest atomic number - Oxygen (O)

  2. Carbon (C) - determine priority based on the next connected atom. Only 1!, not the whole thing

  3. Proton (H) has the lowest atomic priority.

• Resolved ties: If two substituents have the same atom, look at the next atom connected to them to establish priority.

Determining R or S Configuration

• Visualization: Imagine holding the molecule in 3D, with the lowest priority group pointing to the back.

• Clockwise or Anticlockwise:

  • Clockwise rotation = R isomer (right)

  • Anticlockwise rotation = S isomer (left)

• Example with Lactic Acid:

  • Assigning groups based on prioritization leads to the determination of whether it is R or S.

Stereoisomers and Enantiomers

• Multiple stereocenters: Each stereocenter contributes to its unique stereoisomer configuration.

• Counting stereoisomers:

  • For a molecule with n stereocenters, the formula is 2^n stereoisomers.

• Example:

  • Lactic acid (1 stereocenter) → 2 stereoisomers

  • Cholesterol (8 stereocenters) → 256 stereoisomers.

• Nature vs. Chemistry:

  • Nature selects specific stereoisomers while synthetic chemists aspire to achieve similar specificity in control over stereochemical outcomes.

Introduction to Stereoisomers

• The complexity of stereochemistry is significant, especially with understanding different types of steroids and stereoisomers.

• This section aims to clarify these concepts, particularly the distinctions between them.

Stereocenters and Stereoisomers

• A molecule with one stereocenter can produce two stereoisomers (a pair of enantiomers).

• Molecules often possess multiple stereocenters; in this case, the number of stereoisomers increases exponentially.

Example of a Molecule with Two Stereogenic Centers

• Given a molecule with two stereogenic centers, we would expect four stereoisomers.

  • The stereoisomers can be represented as:

    • RR (both stereocenters in R configuration)

    • SS (both stereocenters in S configuration)

    • RS (one R and one S)

    • SR (one S and one R)

• Taking the mirror image of these forms results in the corresponding enantiomers:

  • RR ⟷ SS (mirror images)

  • RS ⟷ SR (mirror images)

Understanding Diastereoisomers

• Diastereoisomers are stereoisomers that are not mirror images of each other, thus cannot be superimposed.

• Example: The pairs of stereoisomers (RR and RS) are diastereoisomers of each other.

• The number of stereoisomers increases significantly with additional stereocenters.

  • For instance, 3 stereogenic centers yield 8 stereoisomers, while 4 yield 16.

Exception: Meso Compounds

• Meso compounds represent a special case in stereochemistry where chirality is not observed despite having stereogenic centers.

• Tartaric acid is a notable example: it has two stereogenic centers but displays a symmetry plane.

  • The RS form of tartaric acid can be superimposed on its mirror image, yielding achiral characteristics.

  • Thus, RR and SS are chiral, while RS and SR are meso forms and identical.

Key Terms

• Chiral Molecules: Have non-superimposable mirror images.

• Achiral Molecules: Can be superimposed on their mirror images.

• Meso Compounds: Are achiral despite having stereogenic centers due to symmetry.

Nature and Chirality

• Enzymes and proteins are inherently chiral, influencing how they interact with different stereoisomers.

• Chiral environments allow specific binding and interactions, showcasing the importance of stereochemistry in biological systems.

Hierarchy of Isomers

• Stereoisomers can be divided into:

  • Constitutional Isomers

  • Stereoisomers:

    • Enantiomers

    • Diastereoisomers

• Conformers and Rotamers are subsets but not covered in detail as they are beyond the exam scope.

Additional Resources

• Recommended videos for further understanding of:

  • The differences between stereoisomers.

  • Meso compounds.

  • R/S nomenclature.