IB chemistry HL revision
Option D
8. Drug action
What is the importance of
geometrical isomerism in drug
action?
Discuss the importance of
chirality in drug action.
Each isomer can have its own (or lack of) pharmacological effects.
Example: diaminedichloro platimum (II) has a square planar
geometry with bond angles of 90 and can therefore show
geometrical isomerism. The cis-isomer, called cisplatin, can act as
an anti-cancer drug as, because of its orientation, it can bond with
DNA in the nucleus of cancer cells. The trans-isomer, transplatin,
does not have any pharmaceutical effects.
Many compounds used as medicines have chirality. Each
enantiomer may have completely different physiological effects, e.g.
one enantiomer of Thalidomide alleviates morning sickness in
pregnant women, while the other enantiomer causes deformities in
the limbs of the fetus.
The effect of stereoisomerism on the development and synthesis of
drugs:
 Each enantiomer must be tested for its physiological effects as its
physiological effect could be different from the other enantiomer.

Modern drugs may have only one enantiomeric form instead of a
racemic mixture. This achieved by using chiral auxiliaries.
What the importance of the
beta-lactam ring action of
penicillin?
The bond angles in the beta-lactam ring structure are only 90° this
puts the beta-lactam ring structure under strain and this makes the
ring structure reactive as it easily breaks open in the amide group,
for instance, in the presence of an enzyme such as transpeptidase,
to form covalent bonds with the transpeptidase. This deactivates the
enzyme that synthesizes the bacterial cell walls, thus inhibiting the
growth of bacterial cell walls. As a result water enters the bacteria
cell causing it to burst due to increased osmotic pressure.
Explain the increased potency
of diamorphine (heroin)
compared to morphine.
Diamorphine is less polar than morphine as it does not have the two
polar hydroxyl group anymore as they have been replaced by two
non-polar ester groups. As a result diamorphine (heroin) cannot form
any hydrogen bonds and is therefore less soluble in polar
substances such as water but more soluble in non-polar fatty tissue,
which makes up the central nervous system, and can therefore cross
the blood-brain barrier faster/more easily than morphine.
9. Drug design
Discuss the use of a
compound library in drug
design.
Compound libraries are databases which contain molecules which
have been isolated or synthesized and tested by pharmaceutical
companies for possible pharmaceutical properties.
Explain the use of
combinatorial chemistry to
synthesize new drugs.
Combinatorial chemistry refers to techniques which allow a very
large number of different but related compounds (many possible
combinations) to be made simultaneously from a small number of
reagents. Compounds are then screened for pharmaceutical
properties and the findings entered into a compound library.
IB revision Option D HL
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Explain the use of parallel
chemistry to synthesize new
drugs.
The synthesis of a smaller but selected group of compounds in
different reaction vessels; It involves producing a reactive
intermediate bonded onto a resin bead which is then introduced into
many different vessels producing a different compound in each
vessel.
What are the advantages of
using solid-phase chemistry in
drug synthesis?
Reagents are adsorbed onto resin beads which allow better mixing
of reagents to make all possible combinations. When synthesis
reactions are complete, the products are removed easily from the
beads by filtering off the beads and washing them.
All reagents are mixed and then split into separate portions i.e. each
portion has all reagents. To each portion a different reagent is added
and a reaction is allowed to occur. The separate portions are then
mixed again after which they are split into separate portion.
To each portion a different reagent is added again…
This is repeated
 Combinatorial libraries: databases used to search for
molecules/groups with required/specific properties. Databases
also include 3D images of molecules.
 3D modeling software can be used to show interaction between
medicine and active site on target molecule/receptor without
actually making the medicine. This also allows them to design
molecules with the perfect fit and then attempt to chemically
produce them.
 Evaluation of (biological/pharmacological) effects of new drugs; if
the structure of a new molecule is known the modeling software
can then test its effectiveness in binding onto a receptor or
enzyme.
 Equally, computers can be used to predict how changes to the
structure of a drug might change its activity. It can do this by 3Dmodeling of the new shape or structure and use the model to find
out how it interacts with target molecule.
What is the split and mix
technique?
Describe how computers are
used in drug design.
Discuss how the polarity of a
molecule can be modified to
increase its aqueous solubility
and how this facilitates its
distribution around the body.
Describe the use of chiral
auxiliaries to form the desired
enantiomer.
IB revision Option D HL
The polarity and therefore solubility in water can be increased by
reacting molecules with acid or amine groups with a strong acid or
alkali and change the molecules into ionic salts. The increased
solubility also improves their uptake.
Examples include aspirin which is reacted with sodium hydroxide to
form an aspirin sodium salt and fluoxetine which is changed into
fluoxetine hydrochloride.
The chiral auxiliary attaches itself to the non-chiral molecule to force
the reaction to follow a certain path i.e. the production of the desired
enantiomer and not the other enantiomer.
Once the new desired molecule has been formed, the auxiliary can
be taken off and recycled.
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10.Mind-altering drugs
Describe the short term
effects of lysergic acid
diethylamide (LSD),
mescaline, psilocybin.
All three cause hallucinations i.e. hearing of voices and seeing of
images which appear realistic but which do not exist i.e. there is no
stimulus for them. The mind-altering drugs disrupt the activity of the
brain transmitter serotonin that is involved in the processing of
hearing and sight.
Describe the effects typical
to..
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What functional groups are
present in all three
hallucinogenics LSD,
mescaline and psilocybin?
What are the structural
differences between LSD,
mescaline and psilocybin?
What is the main ingredient of
cannabis?
What arguments can be used
to support legalization of
cannabis?
What are arguments against
the legalization?
What are the effects of
tetrahydrocannabinol?
IB revision Option D HL
LSD: psychological dependence, effects of LSD may be
experienced a year or more later after last use i.e. “flashbacks”
Mescaline: nausea, trembling, liver damage and reduced appetite
Psilocybin: feelings of relaxation, develop tolerance, sense of
well-being
Benzene ring and amine groups.
Use the data booklet to answer this!!!
tetrahydrocannabinol
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no more or less damaging than other ‘legal’ drugs e.g. alcohol,
tobacco
offers pain relief from certain diseases such as AIDS and cancer
relieves nausea in chemotherapy
relieves tension and anxiety in terminally ill patients
helps decrease pressure inside eyeball in patients suffering from
glaucoma
better control of quality of cannabis
reduction of crime
harmful effects:
o may suppress immune system
o respiratory ailments
reduces ability to drive
causes dependence
the possibility of cannabis users moving on to harder drugs.
loss of sense of time
confusion
light-headedness
sense of floating
loss of inhibitions
euphoria
mental relaxation
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