Stereochemistry is the study of the spatial arrangement of atoms within molecules and how this arrangement affects the physical and chemical properties of substances. For the MCAT, mastering stereochemistry is crucial, as it helps predict the behavior of molecules in biological systems, particularly in enzymatic reactions and drug interactions.

Free MCAT Practice Test

Learning Objectives

In studying stereochemistry for the MCAT, you should be able to differentiate between types of isomers, including structural isomers and stereoisomers (enantiomers, diastereomers). You need to recognize chirality and assign absolute configurations (R/S) using the Cahn-Ingold-Prelog rules. You should also understand how optical activity is measured, the effects of stereochemistry on reactivity, and the importance of stereochemistry in biological systems, particularly with enzymes and receptors.

What is Stereochemistry?

Stereochemistry refers to the three-dimensional arrangement of atoms in a molecule and the impact of this arrangement on its chemical properties. Molecules that differ only in the spatial arrangement of their atoms are called stereoisomers. Stereochemistry plays a critical role in the functionality of molecules, particularly in pharmaceuticals, where different isomers can have vastly different effects on the human body.

Types of Stereoisomers

Enantiomers: Non-superimposable mirror images. These molecules are chiral, meaning they have a “handedness.” Enantiomers have identical physical properties except for the direction in which they rotate plane-polarized light (one rotates it clockwise, the other counterclockwise).

Diastereomers: Stereoisomers that are not mirror images of each other. They differ in physical properties and can have different chemical reactivities.

Meso Compounds: These are achiral molecules despite having stereocenters. Meso compounds have an internal plane of symmetry that makes them superimposable on their mirror images.

Chirality and R/S Nomenclature

A molecule is chiral if it cannot be superimposed on its mirror image. To assign the absolute configuration of chiral centers, we use the Cahn-Ingold-Prelog (CIP) priority rules, which involve:

Assigning priorities to the four groups attached to the stereocenter based on atomic number.
Rotating the molecule so that the group with the lowest priority is in the back.
Determining the direction of the remaining three groups, going from highest to lowest priority. If the sequence is clockwise, the configuration is R (rectus); if counterclockwise, it is S (sinister).

Optical Activity

Chiral molecules can rotate plane-polarized light. This property is called optical activity. A molecule that rotates light clockwise is dextrorotatory (denoted as (+)), while one that rotates light counterclockwise is levorotatory (denoted as (−)). The specific rotation depends on the molecule and its concentration.

Stereochemistry in Biological Systems

Stereochemistry is crucial in biology. Many biomolecules, such as amino acids and sugars, are chiral, and biological systems are highly stereospecific. For example, enzymes and receptors often interact with only one enantiomer of a molecule. This explains why one stereoisomer of a drug can be effective while another may be inactive or even harmful.

Examples

Example 1: Lactic Acid ( $ \text{CH}_3\text{CH}(OH)\text{COOH} $ )

Lactic acid has a chiral center at the carbon bearing the hydroxyl group. The two enantiomers of lactic acid are:

(R)-lactic acid, which is found in muscle cells.
(S)-lactic acid, which is found in sour milk.

Example 2: 2-Butanol ( $ \text{CH}_3\text{CH}_2\text{CH(OH)}\text{CH}_3 $ )

2-Butanol has one chiral center and exists as two enantiomers:

(R)-2-butanol
(S)-2-butanol These enantiomers rotate light in opposite directions and have different effects in biological systems.

Example 3: Tartaric Acid ( $ \text{HOOC-CH(OH)-CH(OH)-COOH} $ )

Tartaric acid has two stereocenters. There are three stereoisomers:

(R,R)-tartaric acid
(S,S)-tartaric acid
Meso-tartaric acid (an achiral meso compound due to its plane of symmetry)

Practice Questions

Question 1:

Which of the following compounds is chiral?

A) Ethanol ( $ \text{CH}_3\text{CH}_2\text{OH} $ )
B) 2-Butanol ( $ \text{CH}_3\text{CH}_2\text{CH(OH)}\text{CH}_3 $ )
C) Acetone ( $ \text{CH}_3\text{COCH}_3 $ )
D) Propanal ( $ \text{CH}_3\text{CH}_2\text{CHO} $ )

Answer: B) 2-Butanol ( $ \text{CH}_3\text{CH}_2\text{CH(OH)}\text{CH}_3 $ )

Explanation: 2-Butanol has a chiral center at the second carbon atom (the carbon bonded to the hydroxyl group). Ethanol, acetone, and propanal do not have stereocenters, so they are not chiral.

Question 2:

What is the relationship between (R)-2-butanol and (S)-2-butanol?

A) Diastereomers
B) Enantiomers
C) Structural isomers
D) Meso compounds

Answer: B) Enantiomers

Explanation: (R)-2-butanol and (S)-2-butanol are non-superimposable mirror images of each other, making them enantiomers.

Question 3:

How many stereoisomers are possible for tartaric acid ( $ \text{HOOC-CH(OH)-CH(OH)-COOH} $ )?

A) 2
B) 3
C) 4
D) 6

Answer: B) 3

Explanation: Tartaric acid has two stereocenters, which could theoretically give four stereoisomers. However, one of these is a meso compound, reducing the number of possible stereoisomers to three: (R,R), (S,S), and the meso form.