Download MedicinesDrugs9 DrugDesign ANSWERS

Chemistry 12 (HL)
Option D.9
Option D.9 – Drug Design
Practice Questions - ANSWERS
1.
Combinatorial chemistry can be used to make polypeptides by a process known as ‘mix and split’.
If four different amino acids are each connected to separate beads then after the first 'mix and split'
there will be a total of 16 different dipeptides formed.
a) How many tripeptides will be present after the next ‘mix and split’? 64
b) How many tetrapeptides will be present after the following ‘mix and split’? 256
n
number of possible structures = 4
(where 4 = number of different amino acids and n = number of mix and split stages)
2.
a) Identify the products in the
reaction vessel marked “?”.
resin-A+C
resin-B+C
resin-C+C
b) Determine the number of
products after stage 4 of mix
and split.
4
3 = 81
c) What is solid phase chemistry and why is it useful?
-
3.
reactants are attached to solid resin beads during the reaction process
starting material covalently bonded to very small (polystyrene) solid beads;
reaction occurs on the surface of the solid resin beads
excess reactants can easily be removed from the reaction mixture by washing and
filtration
purification of the product is relatively easy by washing and filtration
product can easily be removed from the resin bead at the end of the process
How does parallel synthesis differ to combinatorial chemistry?
- parallel synthesis can produce smaller and more focused libraries than combinatorial chemistry
- parallel synthesis is performed in different reaction vessels while combinatorial synthesis is
performed in the same reaction vessel (and so requires separation of the different products)
Chemistry 12 (HL)
Option D.9
RELATED QUESTION: Why is combinatorial chemistry and why is it useful?
-
techniques, such as split and mix, used to produce random combinations
chemical building blocks joined to each other in many combinations
produces large variety of related molecules for compound libraries
uses automated processes for efficient and quick production of new substances
can use very small amounts of reactants
new molecules may be screened for physiological activity or effectiveness as drugs
ANOTHER RELATED QUESTION: Describe the “mix and split” process.
-
4.
starting materials (covalently) bonded to resin beads/solid phase;
reagents mixed together then split into portions;
mixed and split again to react with new reactants;
process repeated until a large compound library of related compounds is produced
State three different ways in which computers are used in the design of new drugs.
These points focus on how the use of computers has improved drug DEVELOPMENT (less emphasis
here on design):
- control amounts of components or reagents added during synthesis
- to make 3-D models of drugs
- develop and evaluate potential drugs virtually (in silico).
- produce virtual libraries
- communicate findings etc.
These points focus on how the use of computers has improved drug DESIGN
- molecular/3-D modelling of receptor sites and drug-receptor interactions
- evaluation of (biological/pharmacological) effects of new drugs;
5.
The structure of aspirin is shown below:
a)
Explain why old tablets of aspirin that have been
left in moist air smell of vinegar.
- esters in aspirin react with water (hydrolyse) to form salicylic acid and ethanoic acid (which
is responsible for the smell of vinegar).
b)
Explain why aspirin is not very soluble in water.
- the non-polar benzene ring and the ester functional group cannot form hydrogen bonds with
water molecules, so solubility is reduced
- carboxylic acid group gives it slight polarity but the effects of the benzene ring and ester are
more pronounced
c)
Explain why aspirin is much more soluble in sodium hydroxide solution than it is in water.
- carboxyl group reacts with sodium hydroxide to form a sodium salt, which is soluble
d)
Write a chemical equation to show how soluble aspirin is produced.
–
+
C8H7O2COOH + NaOH  C8H7O2COO Na + H2O
Chemistry 12 (HL)
e)
Option D.9
Explain what happens when soluble aspirin enters the stomach.
- soluble aspirin  carboxylic acid group is present as its anion
–
+
- the carboxylate group (–COO ) accepts an H from HCl in stomach
6.
The structure of morphine is shown below.
a) State the molecular formula of morphine.
C17H19O3N
b) Write an equation to show the reaction of morphine with hydrochloric acid.
+
C17H19O3N + HCl  C17H19O3NH Cl
–
c) Explain why morphine is often administered as its hydrochloride salt.
d)
7.
morphine is largely a non-polar molecule due to the ether group and the large amount of
hydrocarbon content even though it has two polar hydroxyl groups
the amine (basic) can be neutralized by HCl to make a more soluble salt
Show where the positive charge will be located when morphine is converted into its
hydrochloride salt.
Explain how and why chiral auxiliaries are sometimes used during the synthesis of new drugs.
- why?
- ensure that only the required enantiomer is formed as different enantiomers may have
different physiological effects (and may be harmful)
- eliminates the need to carry out the separation of the desired enantiomer from a racemic
mixture
- how?
-
chiral auxiliary = a chiral molecule (or an enantiomer)
chiral auxiliary bonds to non-chiral reactant near its reactive site
chiral auxiliary creates sterochemical conditions that allow only one enantiomer to form
chirla auxiliary is removed leaving the desired enantiomer
Chemistry 12 (HL)
8.
Describe how computer aided design is used in drug design and development.
The focus here is on the computer aided DESIGN:
-
can model (three-dimensional) shape drug molecule
can model interaction of the drug with target molecule
can predict how changes affect interaction with target molecule
can evaluate effects of new drugs
Option D.9