(b) What are their IUPAC names?

(c) For both drugs, indicate any polar bonds using partial charge symbols (- and +)
as well as dipole arrows.

H
O H H
N N
O H
H H O
O O

Mesalazine Paracetamol

3. CH4 and CBr4 both have a molecular dipole moment of 0 D. Why, then, does CH2Br2
have a non-zero dipole moment?

H Br Br
H C H Br C Br H C H
H Br Br

4. Draw skeletal structures for the following compounds:

(a) 3-Hydroxynonanoic acid

(b) 4-Methylcyclohex-1-ene
 (c) 3,4,4,5-Tetramethylcyclohexa-2,5-dien-1-one (also known as penguinone)

Part 2

Functional groups and intermolecular interactions of local anaesthetics

Introduction

This workshop aims to reinforce the material put forward in the Discoveries 2.3-2.4 and the
applications discussed in the Interactive Lectures 2.5 and 2.6. The concepts covered
include:

(i) Functional groups

(ii) Intermolecular interactions

Instructions

This is a team-based activity. You will work in your allocated teams.

In the workshop you will work through activities related to the above topics.
1) Given the molecular formula and functional group(s) present in each case, draw all
possible structures in skeletal form:

a) C4H11N, containing a tertiary or primary amine functional group

b) C3H6O2, containing an ester functional group

c) C5H9N, containing a nitrile functional group

 d) C5H8O, containing both an aldehyde and alkene functional group

2) Your TA will assign one drug to your team. The drugs are all local anaesthetics.

Many local anaesthetics are structurally related to cocaine.

The local anaesthetics that we will look at today are: benzocaine, lignocaine, procaine,
bupivacaine, mepivacaine, tetracaine and etidocaine.

For the drug allocated to your team please:

a) Find and draw the structure of your assigned anaesthetic and cocaine
b) Classify all functional groups present in both compounds

c) What is the hybridization state of each C, N and O atom?

 d) Indicate the hydrophilic and hydrophobic parts of the drugs

e) Discuss the similarities and differences between your drug and cocaine in terms of
the types and positioning of the functional groups as well as the hydrophilic and/or
hydrophobic parts of the molecules

Answer:

Benzocaine and cocaine are very similar in terms of hydrophilic/

hydrophobic functional groups and their positions. Ester and
amine groups that are hydrophilic and may form hydrogen bonds
in water/with proteins during interactions, while benzene rings
are hydrophobic and may contribute to π stacking with other
aromatic rings in proteins.

3) Escitalopram and venlafaxine are commonly prescribed antidepressants.

a) Draw the skeletal structures of escitalopram and venlafaxine.

b) Classify all functional groups present in both compounds.

c) Indicate any polar bonds using partial charge symbols (- and +).

d) What types of intermolecular interactions might the various parts of escitalopram

and venlafaxine form with water, and with a target protein?
4) The cholesterol-lowering agents called “statins”, such as simvastatin, pravastatin and
atorvastatin, are amongst the most widely prescribed drugs in the world, with annual
sales estimated at about $15 billion.

a) Identify the functional groups in each of these statins.

b) Choose one of the statins and draw out a diagram showing all of the hydrogen
bonds it could theoretically form with water.
 c) Based on the table of water-solubilizing potentials below, would you expect that
pravastatin, as drawn above, would be water-soluble?

Table 1. A generalized list of common hydrophilic and hydrophobic functional groups (Foye WO et al., 2013).

Functional Monofunctional Polyfunctional

group molecule molecule

Alcohol 6 carbons 4 carbons

Phenol 7 carbons 4 carbons
Ether 5 carbons 2 carbons
Aldehyde 5 carbons 2 carbons
Ketone 6 carbons 2 carbons
Amine 7 carbons 3 carbons
Carboxylic acid 6 carbons 3 carbons
Ester 6 carbons 3 carbons
Amide 6 carbons 3 carbons
Single charge 20-30 carbons

d) How might one improve the water solubility of pravastatin and atorvastatin?
Search online and see if you can find evidence that this strategy is used in practice.
Draw the structures of the more water-soluble forms and explain why they are more
water-soluble than the forms shown above in terms of intermolecular interactions.

Answer:

According to multiple resources, atorvastatin is converted to a salt

(mostly calcium and sodium) from its original carboxylic acid form to be
more soluble as it becomes an ion.

Also, adding more hydrophilic functional groups and modifying

molecular structure in favour of hydrogen bonding are both effective in
solubility improvement; despite the improved molecule will be a new
drug.
 Additional Assessable Questions

1. Look up the chemical structure of fluoxetine (Prozac), an antidepressant of the selective

serotonin reuptake inhibitor (SSRI) class.

(a) Draw fluoxetine in skeletal form. Show any lone pairs of electrons in the structure.

(b) On the structure, circle all the oxygen and nitrogen atoms that are sp3 hybridised.
Indicate the atoms that are sp2 hybridised with arrows.

2. Draw all possible structures (in skeletal form) that satisfy the following:

(a) Molecular formula C4H11N, containing a secondary amine functional group.

(b) Molecular formula C5H8O, containing both a ketone and alkene functional group.