W2.4_Isomerism

Question 1

Explain why geometrical isomerism could only occur in unsaturated compounds.

Answer 1

• Saturated: no π bonds between C-C allows rotation
• Unsaturated: π bonds between C=C require a lot of energy to break -> restricted rotation/no interconversion

Question 2

Describe the Cahn-Ingold-Prelog priority rules in gemoetrical isomers.

Answer 2

• High atomic number of atom attached directly to alkene
• Higher atomic number total of atoms attached to the above atom
• Duplicate/triplicate the sum if double/triple bonds are present
• Compare priority on each side
  Same side = cis/Z configuration
• Different side = trans/E configuration

Question 3

Name some exceptions in geomterical isomerism and its pharmacological importance.

Answer 3

• Some C=C is constrained by heterocycles -> X geometrical isomers
• Pharmacological importance: show different biological activities/potencies in drugs (ex. Tamoxifen)

Question 4

What are enantiomers? Describe the Cahn-Ingold-Prelog priority rules in stereoisomers.

Answer 4

• 4th priority group (most likely -H) must be directed backwards
• Clockwise direction: R configuration
• Anti-clockwise direction: S configuration

Question 5

Explain the optical properties in enantiomers and its relation to the formula. Explain what a racemic mixture is.

Answer 5

• Enantiomers have identical physical properties except direction of rotation of plane polarised light
• Optically active (measured in polarimeter) (clockwise + / anti-clockwise -)
• [α.]=α/(c*l)
• [α.] : specific rotation
• α: observed rotation
• c: concentration of sample (g/mL)
• l: length of sample tube (dm)
• Racemic mixture: equal mixture of (+) and (-) enantiomers -> optically inactive with α AND [α.] = 0

Question 6

In molecules with two chiral centres, explain what diastereoismers are.

Answer 6

• Stereoisomers that are not mirror images of one another
• Number of stereoisomers: 2^n (n = no. of chiral centres, in case of no symmetry)

Question 7

Describe how stereoisomerism relate to pharmacological activity of medicines.

Answer 7

• Enzyme inhibitor, receptor antagonist/agonist require binding of drugs to proteins (only made up of natural L-amino acids)
• As binding sites in proteins are chiral, enantiomers of drug bind differently to proteins
• One will bind more effectively than the other
• Some may even have different biological actions