Chirality and Isomerism Overview

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Questions and Answers

What designates the Z geometry of tamoxifen?

It allows tight binding to estrogen receptors. (correct)

It prevents inhibition of signalling.

It weakens drug efficacy.

It enhances cell growth.

What does the 'E' designation in alkene geometry indicate?

Non-polar bonds.

Cyclic structures.

Priority groups on the same face.

Priority groups on opposite faces. (correct)

What is an example of a racemic mixture?

A mixture of one enantiomer only.

A 1:1 mixture of two non-superimposable mirror images. (correct)

A mixture of diastereoisomers.

A chiral compound with no optical activity.

Why is stereoisomerism important in the pharmaceutical industry?

It can lead to major changes in drug efficacy and safety. Signup and view all the answers

What is a characteristic of stereoisomers?

They arise from asymmetry around a carbon atom. Signup and view all the answers

Which term is NOT considered synonymous with chirality?

Optical inactivity. Signup and view all the answers

What is the effect of the correct geometry on pharmaceuticals?

It correlates to greater potency. Signup and view all the answers

What is true about constitutional isomers?

They possess different chemical and pharmaceutical properties. Signup and view all the answers

Which of the following statements regarding geometric isomers is correct?

Trans isomers typically have a higher melting point than cis isomers. Signup and view all the answers

What does the prefix Z represent in IUPAC nomenclature?

Substituents are located together on the same face. Signup and view all the answers

What can be inferred about fumaric acid based on its geometry?

It has E geometry because priority groups are on opposite faces. Signup and view all the answers

What is a characteristic of constitutional isomers?

They have different arrangements of atoms. Signup and view all the answers

What is the first step when determining the configuration of a chiral carbon?

Ensure the chiral carbon is drawn in 3D with wedge bonds Signup and view all the answers

How are atoms attached to the chiral carbon prioritized?

By their atomic number Signup and view all the answers

If two atoms attached to the chiral carbon are the same, what should be done next?

Look at the next atoms attached until a difference is found Signup and view all the answers

Which configuration does the order 1→ 2→ 3 clockwise indicate?

R configuration Signup and view all the answers

In determining the configuration of acebutolol, which atom has the highest priority?

Oxygen Signup and view all the answers

What action should be taken if the priority 4 atom is not at the back?

Rotate the molecule to position it correctly Signup and view all the answers

When analyzing acebutolol, what determines the direction of priority order?

The atomic numbers of the atoms directly attached Signup and view all the answers

If the order of atoms around the chiral carbon is 1→ 2→ 3 anticlockwise, what configuration is present?

S configuration Signup and view all the answers

During the analysis of acebutolol, what distinguishes the two CH2 groups attached to the chiral carbon?

The nitrogen and oxygen atoms they are attached to Signup and view all the answers

What is a requirement for a carbon atom to be classified as chiral?

It must be sp3 hybridised with four different groups attached. Signup and view all the answers

Which statement correctly describes the nature of enantiomers?

They are non-superimposable mirror images. Signup and view all the answers

According to the Cahn-Ingold-Prelog rules, what does a clockwise arrangement of groups around a chiral carbon indicate?

The chiral carbon is designated as R. Signup and view all the answers

How can you determine if a compound is achiral?

If its mirror image is superimposable. Signup and view all the answers

What type of carbon is found in the structures of most chiral compounds?

sp3 hybridised carbon. Signup and view all the answers

Which of the following pairs of compounds can be classified as enantiomers?

Two compounds with mirror image structures that are non-superimposable. Signup and view all the answers

What does a designation of 'S' signify in chiral compounds?

A counterclockwise order of groups around the chiral carbon. Signup and view all the answers

What is the primary characteristic of chiral molecules?

They can exist as non-superimposable mirror images. Signup and view all the answers

Which of the following is NOT a characteristic of enantiomers?

They are superimposable upon their mirror images. Signup and view all the answers

Study Notes

Chirality (Abridged)

This presentation provides an overview of chirality, a key concept in understanding the structure and function of pharmaceutical molecules.
It covers constitutional isomerism, geometric isomerism (cis and trans), IUPAC nomenclature (Z and E), stereoisomerism, and an introduction to chiral carbons.
The information is presented in an abridged format, providing a condensed summary of the topic.
It emphasizes the importance of chirality in determining the function and efficacy of drugs.

Constitutional Isomerism

Constitutional isomers, also called structural isomers, are molecules with the same chemical formula but different connectivity of carbon atoms.
They have different physical and chemical properties, including melting point, boiling point, solubility, and density.
Different connectivity leads to varying functional groups within the molecules.
Constitutional isomers cannot interconvert.

Example of C₉H₈O₄ Isomers

Aspirin (plant/synthetic origin), a non-steroidal anti-inflammatory drug (NSAID), has analgesic, antipyretic, and antiplatelet properties.
Caffeic acid, a plant-derived compound, is a key intermediate in lignin biosynthesis with anti-cancer and antioxidant properties.
4-Hydroxyphenyl-pyruvic acid is found in animals and is an intermediate in the metabolism of tyrosine. If not processed efficiently excess can become toxic.

Geometric Isomerism (Cis and Trans)

Geometric isomers have the same chemical formula and connectivity, but differ in the spatial arrangement of their substituents around a double bond (alkene).
Two geometric isomers are cis and trans isomers. Cis isomers have substituents on the same side of the double bond; trans isomers have substituents on opposite sides of the double bond.
Isomers are not interconvertible between cis and trans forms at ambient or body temperatures.

Examples of C₄H₄O₄ Isomers (Maleic and Fumaric Acid)

Maleic acid (cis-form) is commonly used as a salt base for medicines in the pharmaceutical industry. Its melting point is 139-140°C.
Fumaric acid (trans-form) is also used as a salt base for medicines in the pharmaceutical industry. Its melting point is 287°C.

IUPAC Nomenclature for Alkenes (Cahn-Ingold-Prelog, CIP Rules)

The CIP rules provide a systematic way to name alkenes.
The prefix 'Z' is used when the two highest priority groups are on the same side of the double bond.
The prefix 'E' is used when the two highest priority groups are on opposite sides of the double bond.

Worked Example: Fumaric Acid

Fumaric acid is an alkene with the molecular formula C₄H₄O₄.
When using the CIP rules, the groups on both sides of the double bond, that have the highest priority dictate whether a molecule is Z or E.
The groups are on opposite sides so it's an E isomer.

Why is Geometry Important?:

The correct Z (trans) geometry of tamoxifen is crucial for tight binding to the estrogen receptor.
This leads to inhibition of cell signals, which prevents breast cancer cell growth.

Stereoisomerism

Stereoisomers are molecules with the same atomic connectivity, but different spatial arrangements.
Stereoisomers are categorized as either enantiomers or diastereomers.
Enantiomers are non-superimposable mirror images, while diastereomers are non-superimposable non-mirror images.
Stereoisomerism is important for the pharmaceutical industry. Incorrect stereochemistry can lead adverse effects in patients.

Terminology

Stereoisomerism is synonymous with chirality.
A chiral carbon atom has four different atoms or groups attached.
A racemic mixture (racemate) is a 1:1 mixture of enantiomers.
Optically inactive implies achirality.
Enantiomers are non-superimposable mirror images, while diastereomers are non-superimposable non-mirror images.

What is a Chiral Carbon?

A chiral carbon atom is sp³ hybridised and has four different atoms or groups attached to it.
Chirality can be determined by whether the molecule is superimposable on its mirror image.
Non-superimposable mirror images are called enantiomers.

Practice: Identify the Chiral Carbons

A series of chemical structures and examples of chiral molecules are presented. Students are encouraged to identify chiral carbons within the molecules.

Nomenclature

The IUPAC system uses CIP rules, assigning R or S configurations to chiral centers.
R configuration is assigned when groups have a clockwise order of decreasing priority, and S when there's an anti-clockwise order.

Steps to Classify Chirality

Steps for determining chiral center configurations (R/S) are detailed.

Worked Example: Acebutolol

A worked example demonstrates the process of identifying the chiral carbon and determining its R or S configuration in acebutolol.

What do we do if Priority 4 Atom not at Back?

Addressing cases where the priority 4 atom is not at the back involves rotating the structure.

Key Messages: Alkene Geometry

Z and E designations are crucial for describing alkene geometry.
The priority of substituents is essential for accurate nomenclature.
Alkene geometry is vital for proper binding to target molecules. Correct geometry contributes to better drug potency.

Interactions with Other Enantiomers

Chiral species (receptors and enzymes) often interact differently with different enantiomers.
The correct enantiomer is crucial, since incorrectly matched shapes lead to poor binding or no binding at all.

Vigabatrin (Sabril®)

Vigabatrin is used in epilepsy treatment.
The (S)-enantiomer is active as an anti-convulsant.
Increases GABA levels to reduce seizures.

Fluoxetine (Prozac®)

Fluoxetine is used in depression treatment.
The (S)-enantiomer is the pharmacologically active form.
Eliminates rapidly to a lower volume from the bloodstream.

Warfarin

Warfarin (a blood thinner) is administered as a racemate.
The (S)-enantiomer is more effective and longer-lasting than the (R) form.

Why are Amines Rarely Chiral?

Amines can undergo inversion and lose their chirality.

Key Messages

Pharmaceuticals often have chiral carbons, creating stereoisomerism.
Enantiomers have opposite rotations of polarized light but the same chemical and physical properties.

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Description

This quiz provides an overview of chirality, focusing on its significance in pharmaceuticals. It covers various types of isomerism, including constitutional and geometric isomerism, along with IUPAC nomenclature. Gain insights into how these concepts impact drug function and efficacy in a concise format.