LECTURE 5

Question 1

Explain the R/S nomenclature system

Answer 1

• Determined by the absolute configuration
• Requires the three-dimensional arrangement of the groups
• Primary method for drugs

Question 2

Define chiral center

Answer 2

A chiral center is an atom in a molecule that is bonded to four different chemical species, allowing the molecule to have a non-superimposable mirror image

Question 3

Explain the d/l nomenclature system

Answer 3

• Determined by optical rotation
• Experimentally determined
• Dependent on the solution condition

Question 4

Explain the D/L nomenclature system

Answer 4

• Determined by the relative configuration to glyceraldehyde
• Obsolete; used only for amino acids and sugars
• Amino acids in proteins (except Gly) are all L -amino acids; most of them are S, but Cys is R

Question 5

How do you determine the R/S notation for a drug from its structure?

Answer 5

1. Determine the priority of the groups attached to the chiral carbon using Cahn-Ingold-Prelog (CIP) priority rule
2. View the molecule with the group of lowest priority away
3. Consider the clockwise or counterclockwise order of the priority of the three remaining groups

Question 6

Define enantiomer

Answer 6

a pair of the stereoisomers that are non-superimposable mirror images

1R, 2S and 1S, 2R
2 changes in R/S configuration

Question 7

Explain how the absolute stereochemistry of a molecule can influence receptor binding

Answer 7

• The more potent enantiomer must be involved in a minimum of three intramolecular interactions with the receptor
  – The same molecule with different stereochemistry may not have the same number of intramolecular interactions and therefore may not be as potent

** ALL binding pockets of receptors are chiral

Question 8

List factors other than receptor binding that result in different biological properties of drug enantiomers

Answer 8

Permeation by transporters
Nonspecific binding to serum proteins
Metabolism

Question 9

Explain the potential issues of racemic mixtures as drugs

Answer 9

The inactive enantiomer could show significant adverse side effects instead of being physiologically inert
Ex. naproxen

Question 10

Define diastereomer

Answer 10

a pair of the stereoisomers that are not mirror images

1R, 2S & 1R, 2R
1 change in R/S configuration

Question 11

What nomenclature is used to differentiate geometric isomers?

Answer 11

E/Z nomenclature (cis / trans)

Question 12

What indicates that a molecule may have a geometric isomer?

Answer 12

the presence of (a) double bond(s)