Dose response curves are determined for each drug.

Outline the significance of range “a”.

Suggest the type of reaction used to convert morphine to codeine.

State and explain the action of opiates as painkillers.

«measures» therapeutic window/margin «of a drug»
OR
range of doses that produce a therapeutic effect without causing toxic effects

Accept “difference between ED₅₀/minimum effective/therapeutic dose «for 50% of population» AND TD₅₀ /toxic dose «for 50% of population»”.

Do not accept “therapeutic index”.

Do not accept “lethal/fatal dose” as this is not LD₅₀.

[1 mark]

«nucleophilic» substitution/S_N

Accept “methylation”.

[1 mark]

work directly on opioid/pain receptors «in brain»

suppress pain impulses in brain/CNS

resemble endorphins/enkephalins/natural chemical painkillers «produced in the brain and spinal cord»

Do not award mark for “resemble hormones”.

[2 marks]

Suggest why aspirin is slightly soluble in water. Refer to section 37 of the data booklet.

Formulate an equation for the conversion of aspirin to a more water soluble derivative.

A student prepares aspirin from salicylic acid in the laboratory, extracts it from the reaction mixture, ensures the sample is dry and determines its melting point.

Suggest why the melting point of the student’s sample is lower and not sharp compared to that of pure aspirin.

Organic molecules can be characterized using infrared (IR) spectroscopy.

Compare and contrast the infrared peaks above 1500 cm⁻¹ in pure samples of aspirin and salicylic acid using section 26 of the data booklet.

The pharmaceutical industry is one of the largest producers of waste solvents.

State a green solution to the problem of organic solvent waste.

presence of «large» benzene/arene ring AND non-polar/hydrophobic
OR
presence of «large» benzene/arene ring AND cannot form H-bond with water

contain COOH/carboxyl/–OH/hydroxyl «and ester group» AND polar/hydrophilic
OR
contain COOH/carboxyl/–OH/hydroxyl «and ester group» AND can form H-bonds with water

Accept “phenyl” for “benzene ring”.

Accept "carboxylic acid" for "carboxyl".

Do not accept "alcohol" for "hydroxyl".

[2 marks]

OR
C₆H₄(OCOCH₃)COOH + NaOH → C₆H₄(OCOCH₃)COONa + H₂O

Charges (O^– and Na⁺) not necessary to score the mark.

Accept net ionic equation.

Accept any strong base in place of NaOH.

[1 mark]

«student’s» sample impure

lattice disrupted/not uniform «due to presence of impurities»
OR
fewer interparticle/intermolecular forces «due to presence of impurities»

Accept converse arguments.

[2 marks]

One similarity:
peak at 2500–3000 «cm^–1»/peak due to O–H/hydroxyl in carboxylic acids
OR
peak at 1700–1750 «cm^–1»/peak due to C=O/carbonyl
OR
peak at 2850–3090 «cm^–1»/peak due to C–H of arene

One difference:
peak at 3200–3600 «cm^–1» in salicylic acid/ peak due to O–H in phenol in salicylic acid
OR
«two» peaks at 1700–1750 «cm^–1» in aspirin AND one peak «in the same area» in salicylic acid

Accept “peak at 1600 cm^–1 for arene/benzene ring” – not in the data booklet.

Accept “2500–3600 cm^–1 «overlapping absorptions of two O–H» in salicylic acid”.

Accept “stronger/broader/split peak at 1700–1750 cm^–1 in aspirin”.

[2 marks]

«use of» alternative solvents such as supercritical/liquid CO₂
OR
use of water «as solvent»
OR
solvent-free reactions «for example, polymerization of propene»
OR
solid-state chemistry
OR
recycle «waste» solvents
OR
catalysis that leads to better/higher yield
OR
reducing number of steps

Do not accept political/regulatory solutions.

“catalysis” not sufficient for mark.

[1 mark]

Compare and contrast the structures of oseltamivir and zanamivir, stating the names of functional groups.

Deduce the wavenumber of one absorbance seen in the IR spectrum of only one of the compounds, using section 26 of the data booklet.

Suggest one ethical consideration faced by medical researchers when developing medications.

One similarity:

both contain amido «group»

One difference:

oseltamivir contains ester «group» AND zanamivir does not
OR
oseltamivir contains amino «group» AND zanamivir does not «but contains a guanidino group»
OR
zanamivir contains carboxyl «group» AND oseltamivir does not
OR
zanamivir contains «several» hydroxyl «groups» AND oseltamivir does not
OR
oseltamivir contains ester «group» AND zanamivir contains carboxyl «group»
OR
oseltamivir contains ester «group» AND zanamivir contains «several» hydroxyl «groups»

Accept “both contain ether «group»” OR “both contain alkene/alkenyl «group»” OR “both contain carbonyl «group»” OR “both contain amino/amine «group»”. Latter cannot be given in combination with second difference alternative with respect to amino group.

Accept “amide/carboxamide/carbamoyl” for “amido”.

Accept “amine” for “amino”.

Accept “carboxylic acid” for “carboxyl”.

Accept “hydroxy/alcohol” for “hydroxyl”, but not “hydroxide”.

[2 marks]

1050–1410
OR
1620–1680
OR
1700–1750
OR
2500–3000
OR
3200–3600
OR
2850–3090
OR
3300–3500 «cm^–1»

[1 mark]

«negative» side-effects of medication on patient/volunteers
OR
effects on environment «from all materials used and produced»
OR
potential for abuse
OR
drugs may be developed that are contrary to some religious doctrines
OR
animal testing
OR
risk to benefit ratio
OR
appropriate consent of patient volunteers

[1 mark]

Zanamivir must be taken by inhalation, not orally. Deduce what this suggests about the bioavailability of zanamivir if taken orally.

Oseltamivir does not possess the carboxyl group needed for activity until it is chemically changed in the body. Deduce the name of the functional group in oseltamivir which changes into a carboxyl group in the body. Use section 37 of the data booklet.

The synthesis of oseltamivir is dependent on a supply of the precursor shikimic acid, which is available only in low yield from certain plants, notably Chinese star anise. State one alternative green chemistry source of shikimic acid.

«oral bioavailability is» low
OR
drug is broken down/pH too low/unable to be absorbed from gut
OR
only a small proportion of the drug «taken by mouth» reaches the target organ

ethoxycarbonyl/carbonyl attached to oxygen

Accept “ester”.

Any one of:

fermentation
OR
microbial production

genetically engineered bacteria/E.coli

sweetgum «seeds/leaves/bark»
OR
pine/fir/spruce tree «needles»
OR
Ginkgo biloba

Accept other specific examples of more plentiful plant sources.

Ranitidine (Zantac) is a drug that inhibits stomach acid production. Outline why the development of this drug was based on a detailed knowledge of the structure of histamine, shown below.

Two other drugs, omeprazole (Prilosec) and esomeprazole (Nexium), directly prevent the release of acid into the stomach. Identify the site of action in the body.

A different approach to treating excess stomach acid is to neutralize it with antacids. Formulate an equation that shows the action of an antacid that can neutralize three moles of hydrogen ions, H⁺, per mole of antacid.

«ranitidine» blocks/inhibits histamine binding to «H2» receptor
OR
ranitidine binds to same «H2» receptors «as histamine»
OR
competes with histamine for binding

proton pump
OR
H⁺ /K⁺ ATPase enzyme

Accept “«secretary surface of» parietal cells”.
Do not accept “stomach/stomach wall”.

Al(OH)₃(s) + 3H⁺ (aq) → Al³⁺ (aq) + 3H₂O (l)
OR
Al(OH)₃(s) + 3HCl (aq) → AlCl₃ (aq) + 3H₂O (l)

Name two functional groups that both zanamivir and oseltamivir contain.

Explain how zanamivir works as a preventative agent against flu viruses.

Circle the side-chain in penicillin on the structure below.

Explain, with reference to the action of penicillin, why new penicillins with different side-chains need to be produced.

State and explain the relative solubility of codeine in water compared to morphine and diamorphine.

State the natural source from which codeine, morphine and diamorphine are obtained.

Any two:
«secondary» carboxamide/amido ✔
ether ✔
carbonyl ✔

Accept amide
Accept amino/amine.
Accept alkenyl/alkene.

Do not accept formula.

«drug» blocks/inhibits «viral» enzyme/neuraminidase/$\mathrm{NA}$ «activity» ✔
prevents virus from leaving/escaping host cells «thus cannot infect other cells» ✔

Do not accept other anti-viral methods (as question is specific to Zanamivir).

 ✔

Accept a circle that does not surround the amido group.

Do not accept a circle that only surrounds the phenol group.

bacterial resistance «to older penicillins/antibiotics» ✔

prevent penicillinase/beta-lactamase/enzyme in bacterium to deactivate/open penicillin/beta-lactam ring ✔

Accept “antibiotic resistant bacteria” but not “antibiotic resistance” for M1.
Accept “reduce allergic reactions from from penicillin” for M2.
Award [1 max] for “increased efficiency” OR “increased stability in GIT”.
Do not accept “bacteria develop tolerance”.

codeine less soluble «in water» than morphine AND more soluble than diamorphine
OR
morphine > codeine > diamorphine «in terms of solubility in water» ✔

more/stronger/greater hydrogen/H bonding «due to more hydroxyl groups leads to greater solubility» ✔

opium poppy/plants/seeds ✔

Accept “poppy” OR “opioid”.

Most students scored both marks here. Some students with incorrect answers gave carboxylic acid/carboxyl, benzene/arene, and ester.

Even when a relevant number of students obtained at least one mark, the quality of the answers was in general low and many evidenced very shallow understanding just repeating information

Many students scored here but a relevant percentage didn't include the amide group. Quite a few students did not know where the side chain is and circled other parts of the molecule.

Many good answers for M1 but only stronger students managed to score the second one. The answers evidenced again shallow understanding that may result from independent learning. Many students gave answers related to how penicillin causes bacteria to burst which is not related to this question. Once again it shows students perhaps memorizing answers without a true understanding of concepts.

M1 was correctly presented but most students focused on the polarity of the molecules and presented long arguments where intermolecular forces were ignored. The concept of water solubility and hydrogen bonding was largely ignored.

Mostly well answered. Student who missed this question were clearly guessing with other natural products presented with the Option D material.

(i) Outline what is meant by the term “ring strain”.

(ii) On the diagram above, label with asterisk/s (*) the carbon atom/s that experience ring strain.

(i) Some antibiotic-resistant bacteria produce a beta-lactamase enzyme which destroys penicillin activity. Suggest how adding clavulanic acid to penicillin enables the antibiotic to retain its activity.

(ii) Populations of antibiotic-resistant bacteria have increased significantly over the last 60 years. Outline why antibiotics such as penicillin should not be prescribed to people suffering from a viral infection.

i

bond angles smaller/distorted
OR
instability resulting from abnormal bond angles
OR
bond angles «approximately» 90° instead of 109.5°/120°

Accept “109/110°” for “109.5°”

ii

asterisks (*) on all 3 lactam ring carbon atoms

Must mark all 3 carbon atoms.
Ignore asterisks on the RHS carbon atoms of the five-membered ring.

i

beta-lactam/four-membered ring «in clavulanic acid» reacts with enzyme/beta lactamase

Accept “acts as enzyme inhibitor/suicide substrate/preferentially binds to enzyme”.

ii

antibiotics not effective against viruses
OR
viruses have no cell wall/cell structure/target structures to attack

increasing exposure of bacteria «to antibiotic» increases resistance

Accept “antibiotics kill beneficial bacteria” for M2.

Two drugs are ranitidine (Zantac) and omeprazole (Prilosec). Outline how they function to reduce stomach acidity.

0.500 g of solid anhydrous sodium carbonate, Na₂CO₃(s), is dissolved in 75.0 cm³ of 0.100 mol$$dm⁻³ sodium hydrogen carbonate solution, NaHCO₃(aq). Assume the volume does not change when the salt dissolves.

HCO₃⁻(aq) $\rightleftharpoons$ CO₃²⁻(aq) + H⁺(aq)             pK_a = 10.35.

Calculate the pH of the buffer solution.

Ranitidine:
Blocks/binds H2-histamine receptors «in cells of stomach lining»
OR
prevents histamine molecules binding to H2-histamine receptors «and triggering acid secretion»

Omeprazole:
inhibits enzyme/gastric proton pump which secretes H⁺ ions «into gastric juice»

Accept “H2 receptor antagonist” for M1.

[2 marks]

[Na₂CO₃] = «$\frac{0.500\text{ g}}{105.99\text{ g}\text{mo}{\text{l}}^{-1}\times 0.075\text{ d}{\text{m}}^3}$=» 0.0629 «mol$$dm⁻³»

«pH = pK_a + log$\frac{[\text{conj base]}}{[\text{conj acid}]}$»

«pH = 10.35 – 0.201 =» 10.15

Alternative method involving K_a may be used to deduce pH in M2.

Award [2] for correct final answer.

-2 marks]

Deduce the structural formula of the by-product of this reaction.

Aspirin crystals are rinsed with water after recrystallization to remove impurities.
Suggest why cold water is used.

The solubility of aspirin is increased by converting it to an ionic form. Draw the structure of the ionic form of aspirin.

Comment on the risk of overdose when taking aspirin as an analgesic, referring to the following values, for a person weighing $70 \mathrm{kg}$:

Minimum therapeutic dose $=0.5 \mathrm{g}$

Estimated minimum lethal dose $=15 \mathrm{g}$

OR

${\mathrm{CH}}_3\mathrm{COOH}$ ✔

Accept full OR condensed structural formula.

to avoid dissolving the crystals/aspirin ✔

Accept “to avoid loss of product” OR “aspirin is less soluble in cold water”.

✔

Accept a positive metal ion next to the $CO{O}^{\mathit{-}}$ such as “$N{a}^{\mathit{+}}\mathit{/}{K}^{\mathit{+}}$”.

Accept “$-ONa/-OK$” without showing the charges.

Accept notations such as “$RCO{O}^{-}$” OR “$RCOONa$” OR “$RCOOK$” but not “$R{O}^{-}$” OR “$RONa$” OR “$ROK$”.

low/medium risk «of overdosing» AND «estimated» lethal dose is $30$ times/much larger than therapeutic dose 

OR

$30$ times the dose results in chance of dying ✔

Accept “$\mathit{30}$ and low/medium risk due to large therapeutic index”.
Do not accept “low/medium risk AND large therapeutic window”.
Do not accept “$\mathit{30}$ times the dose” alone for the mark.

A well answered question. Most candidates chose to enter the full structure. Some incorrect answers gave the aspirin product or the salicylic acid rather than the acetic acid.

While there were many good answers it was worrying to correct as many where the student clearly didn't establish a connection between solubility and purification. Many incorrect responses indicated the cold water was to "stay below the melting point of the aspirin" rather than relate it to the solubility of the final product.

Not well answered. Students evidenced familiarity with the content but failed to provide correct structures. Showing lines used to represent covalent bonds to show an ionic interaction, using convention for complexes, showing only one ion were some of the many mistakes. Many students also had an incorrect product having the aspirin lose the -OH group from the carboxylic acid or the entire carboxylic acid functional group rather than just the H⁺.

This is a topic that continues to challenge students and "low/medium risk AND large therapeutic window" was worryingly common. There were also many students who did not calculate the ratio correctly.

Calculate the pH of the buffer from the following data and section 1 of the data booklet.

pK_a(CO₂) = 6.34

[HCO₃⁻(aq)] = 1.40 × 10⁻² mol$$dm⁻³

[CO₂(aq)] = 1.25 × 10⁻³ mol$$dm⁻³

Explain the effect of a large amount of aspirin on the pH of blood.

«pH = pK_a + log₁₀ $\left(\frac{\left[\text{HC}{{\text{O}}_3}^{-}\right]}{\left[\text{C}{\text{O}}_2\right]}\right)=6.34+{\log }_{10}(11.2)=6.34+1.05$» = 7.39

[1 mark]

H⁺ from aspirin reacts with HCO₃⁻ to form CO₂ and H₂O
OR
H⁺(aq) + HCO₃⁻(aq) $\rightleftharpoons$ CO₂(aq) + H₂O(l)
OR
reverse reaction favoured «to use up some of the H⁺ added»

pH decreases

No mark for “stating aspirin is a weak acid that dissociates partially to produce H⁺” without reference to reaction with HCO₃⁻ or to the equation.

Reversible arrows not required for the mark.

Do not accept “small pH change when small amount of H⁺ is added”.

[2 marks]

State the names of two functional groups that both compounds contain, using section 37 of the data booklet.

Explain how oseltamivir and zanamivir can stop the spread of the flu virus in the body.

Any two of:

amido

ether

carbonyl

Accept “amide/carboxamide”.

Accept “alkenyl/alkene”.

Accept “amino/amine”.

[Max 2 Marks]

by preventing the virus from leaving the host cell

by inhibiting viral enzymes/neuraminidases «needed to release virus»

Suggest one problem associated with chlorinated organic solvents as chemical waste.

Suggest how the principles of green chemistry can be used to solve the environmental problems caused by organic solvents.

Any of:

«most are» toxic «to living organisms»
OR
incomplete combustion/incineration can produce toxic products/dioxins/phosgene
OR
carcinogenic

«some can be» greenhouse gases

ozone-depleting

can contribute to formation of «photochemical» smog

accumulate in groundwater
OR
have limited biodegradability

cost/hazards of disposal

Do not accept “harmful to the environment”.

Do not accept just “pollutes water”.

[1 mark]

use organic solvent-free synthetic methods
OR
use water as a solvent
OR
based on atom economy
OR
recover/reuse solvents

[1 mark]

Calculate the amounts, in mol, of each reactant.

Calculate, in g, the theoretical yield of aspirin.

State two techniques which could be used to confirm the identity of aspirin.

State how aspirin can be converted to water-soluble aspirin.

Compare, giving a reason, the bioavailability of soluble aspirin with aspirin.

n(salicylic acid) = «$\frac{2.65\text{ g}}{138.13\text{ g}\text{mo}{\text{l}}^{-1}}$» 0.0192 «mol»

AND

n(ethanoic anhydride) = «$\frac{2.51\text{ g}}{102.10\text{ g}\text{mo}{\text{l}}^{-1}}$» 0.0246 «mol»

[1 mark]

«mass = 0.0192 mol x 180.17 g$$mol^–1 =» 3.46 «g»

Award ECF mark only if limiting reagent determined in (i) has been used.

[1 mark]

Any two of:

melting point

mass spectrometry/MS

high-performance liquid chromatography/HPLC

NMR/nuclear magnetic resonance

X-ray crystallography

elemental analysis «for elemental percent composition»

Accept “spectroscopy” instead of “spectrometry” where mentioned but not “spectrum”.

Accept “infra-red spectroscopy/IR” OR “ultraviolet «-visible» spectroscopy/UV/UV-Vis”.

Do not accept “gas chromatography/GC”.

Accept “thin-layer chromatography/TLC” as an alternative to “HPLC”.

[2 marks]

react with NaOH

Accept “NaHCO₃” or “Na₂CO₃” instead of “NaOH”.

Accept chemical equation OR name for reagent used.

[1 mark]

«marginally» higher AND increase rate of dispersion
OR
«marginally» higher AND increase absorption in mouth/stomach «mucosa»
OR
«approximately the» same AND ionic salt reacts with HCl/acid in stomach to produce aspirin again

Do not accept “«marginally» higher AND greater solubility in blood”.

[1 mark]

Outline the difference between the therapeutic index in animal studies and the therapeutic index in humans.

State the method of drug administration that gives the maximum bioavailability.

in animal studies $\frac{\text{LD50}}{\text{ED50}}$ AND in humans $\frac{\text{TD50}}{\text{ED50}}$

OR

in animal studies lethal dose/LD50 AND in humans toxic dose/TD50

intravenous/IV «injection»

OR

injection into the bloodstream

Aspirin is a mild analgesic derived from salicylic acid found in willow bark.

Describe how mild analgesics function.

The strong analgesics morphine and codeine are opiates. Outline how codeine can be synthesized from morphine. The structures of morphine and codeine are in section 37 of the data booklet.

Explain why opiates are addictive.

prevents/interferes with the production of prostaglandins

OR

prevents/interferes with the production of substances responsible for

inflammation/pain/fever

at the site of injury/source of pain

react with CH₃I/methyl iodide «in alkaline solution»

Accept “react with CH3Cl/methyl chloride” OR “react with methyl halide”.

Accept name or formula of a suitable specific methylating reagent (eg trimethylphenylammonium chloride etc.).

Accept “hydroxy/alcohol” but not “hydroxide” for “hydroxyl”.

Any two of:

interact with opioid receptors in the brain

alter the structure of brain cells

OR

alter the way the brain works «so that it only works normally when the opiates are present»

OR

prevents transmission of pain impulses inside the brain

release dopamine «that the person craves»

OR

give a feeling of pleasure/euphoria «that the person craves»

withdrawal symptoms «prevent patient from terminating drug use»

Accept specific withdrawal symptoms.

[Max 2 Marks]

Outline how oseltamivir (Tamiflu^®) works.

Oseltamivir was commercially produced from shikimic acid, a precursor which is a metabolite in micro-organisms and plants.

Outline how green chemistry was used to develop the precursor for oseltamivir in order to overcome a shortage of the drug during the flu season.

Suggest why the administration of antibiotics to humans and animals can affect the environment.

«drug» blocks/inhibits «viral» enzyme/neuraminidase/NA «activity»

prevents virus from leaving/escaping host cells «thus cannot infect other cells»

[2 marks]

ALTERNATIVE 1:
«using» genetically modified/GM E. Coli/bacteria/microorganisms

E. Coli/bacteria biosynthesis
OR
E. Coli/bacteria «overfed by glucose» undergo fermentation
OR
cells of the bacteria «are broken down to» form precursor/shikimic acid

ALTERNATIVE 2:
use readily available cyclic ester/lactone

forms «the correct stereoisomer of oseltamivir» in a shorter number of chemical steps

Do not accept “planting more Chinese star anise” or “other plant sources of shikimic acid”.

[2 marks]

«can develop antibiotic» resistance in bacteria/microorganisms
OR
changes in microbial/bacterial population

Accept secondary effects, such as reduced biodiversity of aquatic/soil ecosystems, denitrification of soil (due to decline in nitrogen-fixing bacteria). No mark for just stating “water contamination”.

No mark for just stating “failure of aquatic/marine environment”.

[1 mark]

Consider the following antacids:

Show that antacid X is more effective, per tablet, than antacid Y.

same reactant mole ratio «in both equations»
OR
$\mathrm{Mg}\left(\mathrm{OH}{)}_2\right(\mathrm{s})+2\mathrm{HCl}(\mathrm{aq})«\to {\mathrm{MgCl}}_2(\mathrm{aq})+2{\mathrm{H}}_2\mathrm{O}(\mathrm{l})»$ AND
${\mathrm{CaCO}}_3\left(\mathrm{s}\right)+2\mathrm{HCl}\left(\mathrm{aq}\right)«\to {\mathrm{CaCl}}_2\left(\mathrm{aq}\right)+{\mathrm{H}}_2\mathrm{O}\left(\mathrm{l}\right)+{\mathrm{CO}}_2\left(\mathrm{g}\right)»$ ✔

${}_{𝑛}\mathrm{Mg}(\mathrm{OH}{)}_2=«\frac{0.200}{58.32}=»3.43\times {10}^{-3}«\mathrm{mol}»$ AND
${}_{𝑛}\mathrm{CaCO}_3=«\frac{0.220}{100.09}=»2.20\times {10}^{-3}«\mathrm{mol}»$ ✔

«tablet of» X neutralizes $6.86\times {10}^{-3}«\mathrm{mol}» \mathrm{HCl}$ AND «tablet of» Y neutralizes $4.40\times {10}^{-3}«\mathrm{mol}» \mathrm{HCl}$ ✔

Award [3] for correct final statement AND values in M3.

Very poorly answered. Many students scored at least 1 point. This was usually M2 by determining the mols
of each antacid present. However, many students totally ignored the corresponding balanced chemical equations or entered wrong ones. A worrying number of candidates didn't therefore use the correct molar ratio to calculate the values in M3. Showing the calculations and how X is more effective than Y was the point of the question.

Radioisotopes are used to diagnose and treat various diseases. Explain the low environmental impact of most medical nuclear waste.

Any two of:

emits weak ionising radiation

OR

low activity/radioactivity

can be stored until material becomes inactive AND then disposed with normal waste

«isotopes» have short lives

OR

exist for a short period of time

Award [1 max] for “low-level waste/LLW”.

[Max 2 Marks]

Explain how ranitidine (Zantac) reduces stomach acid production.

The pH is maintained in different fluids in the body by the use of buffers.

Calculate the pH of a buffer solution of 0.0200 mol dm^–3 carbonic acid, H₂CO₃, and 0.400 mol dm^–3 sodium hydrogen carbonate, NaHCO₃. The pK_a of carbonic acid is 6.35.

blocks/binds to H2/histamine receptors «in cells of stomach lining»

OR

prevents histamine binding to H2/histamine receptors «and triggering acid secretion»

prevents parietal cells from releasing/producing acid

Accept "H2-receptor antagonist/H2RA" OR "blocks/inhibits action of histamine" for M1.

ALTERNATIVE 1

pH = «pK_a + log $\frac{\left[{\text{A}}^{-}\right]}{\left[\text{HA}\right]}$ =» 6.35 + log ($\frac{0.400}{0.0200}$)

«pH =» 7.65

ALTERNATIVE 2

K_a = 4.5 x 10^–7

«K_a = 0.400 x $\frac{\left[{\text{H}}^{+}\right]}{0.0200}$, [H⁺] =» 2.3 x 10^–8 «mol dm^–3»

«pH =» 7.64

Award [2] for correct final answer.

Do not accept “pH = 8”.

Molecules of antibiotics often contain a beta-lactam ring. Explain the importance of the betalactam ring in the action of penicillin, using section 37 of the data booklet.

ring is «sterically» strained

OR

angles of 90° instead of 109.5/109/120° angles

OR

angles smaller than 109.5/109/120°/tetrahedral/trigonal planar/triangular planar angle

ring breaks up/opens/reacts «easily»

OR

amido/amine group «in ring» is «highly» reactive

binds to/reacts with/interferes with/inactivates transpeptidase

OR

binds to/reacts with/interferes with/inactivates enzyme responsible for bacterial cell wall formation/cross-linking

Describe how penicillin combats bacterial infections.

State how penicillins may be modified to increase their effectiveness.

State the type of reaction used to synthesize aspirin from salicylic acid.

Explain why aspirin is not stored in a hot, humid location.

«irreversibly» binds/bonds to enzyme/transpeptidase

OR

inhibits enzyme/transpeptidase «in bacteria» that produces cell walls

OR

prevents cross-linking of bacterial cell walls

cells absorb water AND burst

OR

cells cannot reproduce

[2 marks]

modify side chain

[1 mark]

condensation

OR

esterification

OR

nucleophilic substitution/nucleophilic displacement/S_N2

Do not accept just “substitution/displacement”.

[1 mark]

water causes hydrolysis

OR

aspirin reacts with water

heat increases the rate of hydrolysis

OR

heat increases the rate of the reaction with water

Accept “aspirin will convert into salicylic/ethanoic acid”.

Do not accept “aspirin dissolves in water” OR “aspirin absorbs water/is hygroscopic”.

[2 marks]

Determine the percentage experimental yield of the product after recrystallization. The molar masses are as follows: M(salicylic acid) = 138.13 g mol⁻¹, M(aspirin) = 180.17 g mol⁻¹. (You do not need to process the uncertainties in the calculation.)

Suggest why isolation of the crude product involved the addition of ice-cold water.

Justify the conclusion that recrystallization increased the purity of the product, by reference to two differences between the melting point data of the crude and recrystallized products.

State why aspirin is described as a mild analgesic with reference to its site of action.

ALTERNATIVE 1:
«theoretical yield = $\frac{1.552\text{g}}{138.13\text{g}\text{mo}{\text{l}}^{-1}}$ × 180.17 g mol⁻¹ =» 2.024 «g»

«experimental yield = $\frac{1.124\mathrm{g}}{2.024\mathrm{g}}$ × 100 =» 55.53 «%»

ALTERNATIVE 2:
«$\frac{1.552\text{g}}{138.13\text{g}\text{mo}{\text{l}}^{-1}}$»= 0.01124 «mol salicylic acid/aspirin theoretical» AND

«$\frac{1.124\text{g}}{180.17\text{g}\text{mo}{\text{l}}^{-1}}$»= 0.006239 «mol aspirin experimental»

«experimental yield = $\frac{0.006239\mathrm{m}\mathrm{o}\mathrm{l}}{0.01124\mathrm{m}\mathrm{o}\mathrm{l}}$ x 100 =» 55.51 «%»

Accept answers in the range 55.4 % to 55.7 %.
Award [2] for correct final answer.

low temperature gives greater difference between solubility of aspirin and impurities
OR
«product» crystallizes out from cold solution/«ice-cold water/lower temperature» speeds up crystallization process
OR
aspirin/product has low solubility «in water» at low temperatures

intercepts pain stimulus at source/acts at site of pain
OR
interferes with production of pain sensitizing substances/prostaglandins «at site of pain»

recrystallized melting point is higher
OR
recrystallized melting point is closer to pure substance/literature value

smaller range of values

Aspirin is often taken to reduce pain, swelling or fever. State one other use of aspirin.

State what is meant by the bioavailability of a drug.

Outline how the bioavailability of aspirin may be increased.

Compare and contrast the IR spectrum of aspirin with that of salicylic acid, using section 26 of the data booklet.

Describe how penicillin combats bacterial infections.

Outline two consequences of prescribing antibiotics such as penicillin unnecessarily.

State how penicillins may be modified to increase their effectiveness.

Morphine and codeine are strong analgesics. Outline how strong analgesics function.

Suggest one reason why codeine is more widely used than morphine as an analgesic.

Any one of:

anticoagulant

lower risk of heart attack/strokes

prevent recurrence of heart attack/stroke

prevents cancer of colon/oesophagus/stomach

Accept “prevents/reduces blood clots” OR “blood thinner”.

[1 mark]

fraction/proportion/percentage «of administered dosage» that reaches target «part of human body»

OR

fraction/ proportion/percentage «of administered dosage» that reaches blood «plasma»/systemic circulation

Accept “the ability of the drug to be absorbed by the body” OR “the extent to which the drug is absorbed by the body”.

Do not accept “the amount/quantity of the drug absorbed”.

[1 mark]

«intravenous» injection/IV

Accept “parenterally”.

Accept “react with alkali/NaOH” OR “convert to ionic form/salt”.

[1 mark]

One absorption found in both spectra:

Any one of:

1050–1410 cm^–1 «C–O in alcohols, esters, ethers»

1700–1750 cm^–1 «C=O in carboxylic acids, esters»

2500–3000 cm^–1 «O–H in carboxylic acids»

2850–3090 cm^–1 «C–H in alkanes, alkenes, arenes»

One absorption found in only one of the spectra:

3200–3600 cm^–1 «O–H in alcohols, phenols»

Award [1 max] if candidate states bonds (C=O in both, O–H in salicylic acid only) but doesn’t quote wavelength ranges.

Accept a second/additional absorption at 1700–1750 cm^–1 from the C=O in ester.

[2 marks]

Any two of:

ring is «sterically» strained

OR

ring breaks up/opens/reacts «easily»

OR

amide/amido group «in ring» is «highly» reactive

«irreversibly» binds/bonds to enzyme/transpeptidase

OR

inhibits enzyme/transpeptidase «in bacteria» that produces cell walls

OR

prevents cross-linking of bacterial cell walls

cells absorb water AND burst

OR

cells cannot reproduce

Award [1 max] for “interferes with cell wall production”.

Do not accept “cell membrane” instead of “cell wall”.

[2 marks]

Any two of:

leads to «bacterial» resistance/proportion of resistant bacteria increases

OR

leads to penicillinase-producing bacteria

damage to/contamination of bodies of water/ecosystems

destroys useful/beneficial bacteria

destroyed bacteria replaced by more harmful bacteria

Accept “endocrine disruptor”.

Do not accept “increased cost of developing antibiotics”.

[2 marks]

modify side chain

[1 mark]

temporarily bind to/block/interfere with receptor sites in brain

OR

prevent transmission of pain impulses within CNS/central nervous system

[1 mark]

codeine has a wider therapeutic window

Accept “codeine has lower activity” OR “codeine has lower risk of overdose” OR “codeine is less potent” OR “codeine has less side-effects”.

Do not accept “lower abuse potential for codeine” OR “less addictive «than morphine»” OR “codeine has a lower bioavailability” OR “available without prescription” OR “cheaper”.

[1 mark]

Identify the names of two functional groups present in zanamivir using section 37 of the data booklet.

Distinguish between bacteria and viruses.

Any two of:

hydroxyl

carboxyl/carbonyl

ether

amido/carbonyl

Accept “alcohol/hydroxy” for “hydroxyl”, “carboxylic acid” for “carboxyl” and “amide/carboxamide” for “amido”.

Accept “amino/amine” OR “imine/imino” but these are not correct as they are part of the guanidino group.

Accept “alkenyl/alkene/carbon to carbon double bond” but not “C=C” OR “carbon double bond”.

Accept “carbonyl” only once.

Accept “heterocyclic ring” for “ether”.

[2 marks]

Any two of:

bacteria perform living functions «on their own» AND viruses do not «without host cell»

bacteria have cell walls AND viruses do not

OR

bacteria do not have a capsid AND viruses do

bacteria larger than viruses

bacteria reproduce by fission/budding AND viruses reproduce within a living host cell

Accept examples of living functionsexcretion, reproduction etc for M1.

Accept “bacteria have flagella/cytoplasm/ribosome AND virus can have head/protein tail/double stranded RNA/single stranded DNA”.

Accept other specific structural differences for M2.

Accept “asexual reproduction for bacteria” for M4.

[2 marks]

Explain why diamorphine (heroin) crosses the blood–brain barrier more easily than morphine.

Describe the analgesic action of an opiate.

Outline the meaning of the bioavailability of a drug.

blood-brain barrier is hydrophobic/non-polar/made of lipids ✔

morphine has hydroxyl/OH «groups»/is more polar AND diamorphine has ester/ethanoate/OCOCH₃/acetate «groups»/is less polar/is lipid soluble ✔

Accept “fats” for “lipid”.

Accept “alcohol/hydroxy” for “hydroxyl” but not “hydroxide”.

Accept “non-polar” for “less polar” in M2.

«temporarily» binds to «opioid» receptor sites in the brain/CNS

OR

«temporarily» suppresses pain impulses in/to the brain/CNS ✔

fraction/proportion/percentage of «administered dosage» enters blood/plasma/circulation ✔

Accept “fraction/proportion/percentage of «administered dosage» that reaches target «part of human body»”.

Oseltamivir (Tamiflu) and zanamivir (Relenza) are used against flu viruses. Explain how these drugs function.

Shikimic acid, the precursor for oseltamivir (Tamiflu), was originally extracted from star anise, and is now produced using genetically modified E. coli bacteria.

Suggest one difficulty associated with synthesizing oseltamivir (Tamiflu) from star anise.

blocks/inhibits neuraminidase/NA/«viral» enzyme which allows viruses to pass through cell membrane

prevent virus from leaving/escaping host cell «thus it cannot infect other cells»

[2 marks]

Any one of:

limited supply of star anise/plant

«star anise» takes time to grow

time-consuming/multi-step extraction

low concentration in plan

Accept “low yield for extraction/conversion” OR “requires environmentally damaging solvents”.

[1 mark]

Drug testing is necessary to determine safe and effective doses.

Distinguish between the lethal dose (LD₅₀) and the toxic dose (TD₅₀).

LD₅₀: amount/dose that kills 50% of the population

TD₅₀: amount/dose that negatively affects/produces toxic effects in 50% of the population

Award [1 max] for “LD₅₀ used in animal trials AND TD₅₀ used in human studies”.

[2 marks]

An antacid tablet contains 680 mg of calcium carbonate, CaCO₃, and 80 mg of magnesium carbonate, MgCO₃.

State the equation for the reaction of magnesium carbonate with hydrochloric acid.

Determine the amount, in mol, of hydrochloric acid neutralized by one antacid tablet.

Explain how omeprazole (Prilosec) reduces stomach acidity.

MgCO₃(s) + 2HCl(aq) → CO₂(g) + H₂O(l) + MgCl₂(aq)

Do not accept “H₂CO₃”.

[1 mark]

n(HCl) = 2 n(CaCO₃) + 2 n(MgCO₃)

OR

n(HCl) = $\frac{2\times 0.680\ll \text{g}\gg }{100.09\ll \text{g mo}{\text{l}}^{-1}\gg }+\frac{2\times 0.080\ll \text{g}\gg }{84.32\ll \text{g mo}{\text{l}}^{-1}\gg }$

«n(HCl) = 0.0136 mol + 0.0019 mol =» 0.016 «mol»

Award [2] for correct final answer.

Award [1 max] for correctly calculating amount of acid neutralized by just CaCO₃ (0.014 «mol») or MgCO₃ (0.002 «mol»).

[2 marks]

inhibits the secretion of stomach acid/H⁺

«active metabolites» bind «irreversibly» to «receptors of the» proton pump

Accept “PPI/proton pump inhibitor”.

Do not award mark for “binds to H2/histamine receptors”. (Ranitidine mode of action.)

Accept “H⁺/K⁺ ATPase” for “proton pump”.

[2 marks]

State the internal bond angles in the β-lactam ring and the expected bond angles for the same atoms in an open structure.

Explain how the open β-lactam ring kills bacteria.

Outline one effect of over-prescription of penicillin.

State how the structure of penicillin can be changed to combat this effect.

Suggest why human cells are not affected by penicillin.

Accept “109º”.

«irreversibly» binds/bonds to enzyme/transpeptidase

OR

inhibits enzyme/transpeptidase «in bacteria» that produces cell walls

OR

prevents cross-linking of bacterial cell walls ✔

cells absorb water AND burst

OR

cells cannot reproduce ✔

Accept “reacts with” for “bonds to” for M1.

Do not accept “cell membrane” for “cell wall” for M1.

Accept “cells burst due to osmotic pressure” for M2.

Accept “bacteria” for “cells” for M2.

Any one of:

leads to «bacterial» resistance «to antibiotics»

OR

makes antibiotics less effective

OR

increased side effects due to larger dosages/over time ✔

increases proportion of resistant bacteria ✔

destroys useful/beneficial bacteria

OR

destroyed bacteria replaced by more harmful bacteria ✔

resistant bacteria pass on their mutation to next generation ✔

damage to ecosystems ✔

Accept “superbugs such as MRSA develop” but superbug must be identified.

Accept “immune” for resistant but do not accept “tolerance”

«modify» side-chain ✔

Accept “«modify» R”.

no cell walls

OR

humans do not have transpeptidase ✔

Determine the pH of a buffer solution that is 0.0100 mol dm⁻³ sodium hydrogen carbonate and 0.0200 mol dm⁻³ sodium carbonate, using section 1 of the data booklet.

K_a (hydrogen carbonate ion) = 4.8 × 10⁻¹¹

State the equation for the reaction of calcium carbonate, the active ingredient in some antacids, with stomach acid.

Suggest a technique for measuring the percentage mass of calcium carbonate in this type of antacid tablet.

ALTERNATIVE 1:

Using: pH = pK_a + log $\left(\frac{\left[A^{-}\right]}{\left[HA\right]}\right)$

pK_a = 10.32 ✔

pH = «10.32 + log $\left(\frac{0.0200}{0.0100}\right)$ =» 10.62 ✔

ALTERNATIVE 2:

[H⁺] «= K_a × $\left(\frac{0.0100}{0.0200}\right)$» = 2.4 × 10⁻¹¹ ✔

pH = 10.62 ✔

Award [2] for correct final answer.

Accept answers for M2 between 10.6 and 10.7.

Award [1 max] for pH = 10.02.

CaCO₃ (s) + 2HCl (aq) → CaCl₂ (aq) + H₂O (l) + CO₂ (g)

OR

CaCO₃ (s) + 2H⁺ (aq) → Ca²⁺ (aq) + H₂O (l) + CO₂ (g) ✔

«back» titration

OR

thermal decomposition

OR

atomic absorption/AA ✔

Accept “gravimetric analysis”.

Do not accept description of a technique without proper term given for the technique.

Describe the proper disposal of low-level radioactive waste in hospitals.

Outline a green chemistry solution for problems generated by the use of organic solvents.

store until material becomes inactive/radiation levels drop ✔

dispose with other waste
OR
dispose in landfills ✔

Only award M2 if M1 correct.
Accept “dispose by incineration” for M2.

«use of» alternative solvents such as supercritical/liquid ${\mathrm{CO}}_2$
Do not accept political or regulatory solutions.
OR
use of water «as solvent»
OR
solvent-free reactions «for example, polymerization of propene»
OR
solid-state chemistry
OR
recycle «waste» solvents
OR
catalysis that leads to better/higher yield
“catalysis” alone not sufficient for mark.
OR
reducing number of steps ✔

Mostly well answered. Some students lost a mark due to not giving a complete answer. In Spanish quite a few students referred to isotopes 'decomposing' and therefore lost their mark.

Many correct answers. The most common correct answer was using water as a solvent. Some students lost the mark with responses like " less dangerous organic solvents", "alternative solvents (but not giving a specific example)" or "proper disposal of organic solvents".

Formulate an equation for the neutralization of stomach acid with calcium carbonate, CaCO₃ (s).

Determine the volume of CO₂ (g), in dm³, produced at STP, when 1.00 g of CaCO₃ (s) reacts completely with stomach acid.

M_r CaCO₃ = 100.09

Acid secretion can be regulated by other types of drugs such as omeprazole and ranitidine. Outline how each of these drugs acts to reduce excess stomach acid. 

Omeprazole:

Ranitidine:

CaCO₃ (s) + 2HCl (aq) → CO₂ (g) + CaCl₂ (aq) + H₂O (l)  [✔]

Note: Accept balanced ionic equations involving “H⁺” or “H₃O⁺”.

Do not accept “H₂CO₃”.

n CaCO₃ = « $\frac{1.00\text{ g}}{100.09\text{ g mo}{\text{l}}^{-1}}$ =» 0.00999 «mol»  [✔]

volume CO₂ = «0.00999 mol × 22.7 dm³ mol^–1 = » 0.227 «dm³»  [✔]

Note: Accept 0.224 «dm³» if 22.4 dm³ mol^–1 is used as molar volume.

Award [2] for correct answer.

Omeprazole:
inhibits enzyme/«gastric» proton pump «which secretes H⁺ ions into gastric juice»
OR
inhibits the H⁺/K⁺-ATPase system  [✔]

Ranitidine:
inhibits/blocks H2/histamine receptors «in cells of stomach lining»
OR
prevents histamine binding to H2/histamine receptors «and triggering acid secretion»  [✔]

Note: Accept “H2-receptor antagonist” for M2.

About two-thirds of the candidates could write an equation for the reaction of calcium carbonate with an acid. It was refreshing to find that “H₂CO₃” was only rarely encountered as a product.

It was encouraging that over half the students were able to calculate the volume of gas produced from a given mass of calcium carbonate.

Many students correctly remembered the modes of action of Omeprazole and Ranitidine, though needless to say a few confused these and weaker students thought they acted like conventional antacids.

Drug synthesis often involves solvents.

Identify a common hazardous solvent and a Green solvent that could replace it.

Hazardous solvent:

Any one of:

methanal/formaldehyde

methanol

chlorinated solvent/carbon tetrachloride/methylene chloride/dichloromethane

diethyl ether/ethoxyethane

benzene

OR

methyl benzene/toluene

OR

«1,2/1,3/1,4» dimethylbenzene/«ortho/o-/meta/m-/para/p-» xylene

Green solvent:

Any one of:

water

«supercritical/liquid» carbon dioxide/supercritical fluids

ethanol «only if replacing a hazardous solvent»

propan-2-ol/2-propanol/isopropanol «only if replacing a hazardous solvent»

propanone/acetone «only if replacing a hazardous solvent»

ethyl ethanoate/ethyl acetate «only if replacing a hazardous solvent»

organic carbonates/dimethyl carbonate/diethyl carbonate/ethylene

carbonate/propylene carbonate

ionic liquids

fluorous solvents

Accept correct names (either IUPAC or generic) or formulas.

Do not accept inorganic acids such as HCl, H₂SO₄, etc.

Accept any specific chlorinated solvent.

Accept other hazardous solvents.

Do not accept any solvent given as both hazardous and green.

Award [2] for combination “Hazardous solvent: dimethylformamide/DMF/N,N-dimethylmethanamide” AND “Green solvent: methanol «only if replacing a hazardous solvent»”.

Accept other green solvents but not “solvents from biomass/food waste”.

[2 marks]

Explain why diamorphine passes more readily than morphine through the blood-brain barrier.

Suggest a reagent used to prepare diamorphine from morphine.

Suggest one reason why codeine is available without prescription in some countries whilst morphine is administered under strict medical supervision.

Any two of:

diamorphine has ester/ethanoate/acetate «groups» AND morphine has hydroxyl «groups»

diamorphine/ester/ethanoate/acetate groups less polar

diamorphine more soluble in lipids

Accept “alcohol/hydroxy” for “hydroxyl” but not “hydroxide”.

Accept “diamorphine non-polar”.

Accept converse statements.

[2 marks]

ethanoic/acetic anhydride
OR
ethanoyl/acetyl chloride

Accept other possible reagents, such as ethanoic/acetic acid or acetyl bromide.

Accept chemical formulas.

[1 mark]

morphine has a smaller therapeutic window

Accept converse statements.

Accept “codeine has lower activity” OR “codeine has lower risk of overdose” OR “codeine is less potent”.

Do not accept “lower abuse potential for codeine” OR “codeine less addictive” OR “codeine has a lower bioavailability”.

[1 mark]

Explain how opiates act to provide pain relief.

Discuss how the difference in structure of two opiates, codeine and morphine, affect their ability to cross the blood–brain barrier. Use section 37 of the data booklet.

«temporarily» bond/bind to «opioid» receptors in the brain/CNS  [✔]

block the transmission of pain impulses  [✔]

«codeine crosses blood–brain barrier more easily»
morphine has more hydroxyl/OH «groups than codeine»  [✔]

codeine/ether group is less polar
OR
hydroxyl/OH «groups in morphine» H-bond to water [✔]

Note: Award [1 max] if no statement or an incorrect statement about the blood–brain barrier.

Most candidates correctly remembered the mode of action strong analgesics, though some had difficulty expressing it clearly.

Many candidates identified the relevant structural difference from the data booklet structures and could use these to explain the difference in the ability of the drugs to reach the brain, though some were confused as to whether this was favoured by aqueous solubility. This again was more frequently discussed in terms of polarity than the ability of –OH groups to form hydrogen bonds.

Aspirin can be obtained from salicylic acid.

Unreacted salicylic acid may be present as an impurity in aspirin and can be detected in the infrared (IR) spectrum.

Name the functional group and identify the absorption band that differentiates salicylic acid from aspirin. Use section 26 of the data booklet.

Name: 

Absorption band:

Name:
hydroxyl  [✔]

Absorption band:
3200–3600 «cm^–1»  [✔]

Note: Accept “phenol” OR “alcohol” but not “hydroxide”.

Many students could correctly identify a difference between the given structures and state a region in the IR spectrum where this would absorb.

Suggest two reasons why chlorinated solvents should neither be released into the atmosphere nor incinerated (burnt).

Any two of:

«weak» C–Cl bonds break/produce radicals ✔

contribute to ozone depletion ✔

contribute to «photochemical» smog ✔

cause cancers ✔

damage respiratory system ✔

cause organ failure ✔

produce toxic chemicals/phosgene/dioxins ✔

Accept “chlorinated solvents are toxic”.

Outline how ranitidine (Zantac) inhibits stomach acid production.

Outline two advantages of taking ranitidine instead of an antacid which neutralizes excess acid.

Some antacids contain carbonates.

Determine the pH of a buffer solution which contains 0.160 mol dm⁻³ CO₃²⁻ and 0.200 mol dm⁻³ HCO₃⁻, using section 1 of the data booklet.

pK_a (HCO₃⁻) = 10.32

blocks/binds H2/histamine receptors «in cells of stomach lining»
OR
prevents histamine molecules binding to H2/histamine receptors «and triggering acid secretion»  [✔]

Any two of:
ranitidine can be effective in treating ulcers «but antacid is not»  [✔]

ranitidine can prevent long-term damage «from overproduction of acid and antacid does not»  [✔]

ranitidine has a long-term effect «and antacid has short-term effect only»  [✔]

ranitidine does not affect ionic balance in body «and antacid does» [✔]

ranitidine does not produce bloating/flatulence [✔]

Note: Accept “ranitidine stops the over production of acid in the stomach while antacids neutralize the excess acid giving temporary relief”.

«pH = pK_a + log $\frac{\text{[}{\text{A}}^{-}]}{[\text{HA]}}$ = 10.32 + log $\frac{0.160}{0.200}$ = 10.32 – 0.097»

«pH =»10.22  [✔]

This question was not very well answered even though it has been seen in previous scripts. Some students were not through enough in their answers to receive a mark while others confused the action of ranitidine which blocks H2 receptors with omeprazole which is a proton pump inhibitor.

While most students were awarded at least one of the two marks possible for this question some of the descriptions were too vague or incomplete to receive a mark.

This was in general a well answered question. Most candidates who did not receive the mark inverted the concentration of the conjugate base/concentration of the acid in the calculation.

Draw a circle around the functional group that can be converted to the carboxylate by hydrolysis.

Suggest a reason for using a phosphate salt of oseltamivir in oral tablets.

Anti-HIV drugs, such as zidovudine, often become less effective over time.

Explain the development of resistant virus strains in the presence of antiviral drugs.

 [✔]

Note: Accept circles that include the alkyl side chain.

more soluble «in water»  [✔]

viruses undergo «rapid» mutation  [✔]

mutation causes a change in viral protein
OR
drug to no longer binds to virus  [✔]

Note: Accept “rapid reproduction «allows resistant viruses to multiply»”.

Many students erroneously identified the amide as the required group, failing to realise that its hydrolysis would give the carboxylate ion of the side chain lost to the drug.

About a third of the candidates realised that producing a salt would increase the drug’s aqueous solubility, though many just stated “increased bioavailability” without explaining how this came about.

Another question where well argued responses were rare, though many students gained credit for mentioning the ease of mutation and the speed of reproduction of viruses.

Distinguish between therapeutic window and therapeutic index in humans. 

Therapeutic window:

Therapeutic index:

State one advantage of using morphine as an analgesic.

Explain why diamorphine (heroin) is more potent than morphine using section 37 of the data booklet.

Therapeutic window:
range of dosage «over which a drug» provides the therapeutic/desired effect without causing adverse/toxic effects [✔]

Therapeutic index:
toxic dose of drug for 50 % of population divided by minimum effective dose for 50 % of population
OR
$\frac{\text{TD50}}{\text{ED}50}$  [✔]

Note: M1 may be scored from a correctly labelled diagram.

Accept “difference between ED50/minimum effective/therapeutic dose «for 50% of population» AND TD50/toxic dose «for 50% of population»” for M1.

Do not accept reference to lethal dose used in therapeutic index in animal studies.

blocks pain impulses/binds with «opioid» receptors in brain/CNS
OR
effective against strong pain
OR
sedate patients to reduce trauma [✔]

Note: Accept “effective against pain after surgery/cancer/following serious injury”.

Accept “relieves anxiety/stress associated with severe/terminal illness”.

morphine has «two» hydroxyl groups AND diamorphine has «two» ester/ethanoate/acetate groups
OR
molecule of diamorphine is less polar than morphine
OR
groups in morphine are replaced with less polar/non-polar groups in diamorphine  [✔]

«less polar molecules» cross the blood–brain barrier faster/more easily
OR
diamorphine is more soluble in non-polar environment of CNS/central nervous system than morphine [✔]

Note: Accept “alcohol/hydroxy” for “hydroxyl” but not ”hydroxide”.

Accept “fats” for “lipid”.

Accept “heroin” for “diamorphine”.

Most students receive one mark for this question and therapeutic window was probably the more successfully mark. Teachers need to remind students not to refer to lethal dose for therapeutic index. Some students forgot to mention the 50/50 % when explaining therapeutic index or inverted the ration as ED50/TD50.

This was not a particularly well answered question even though it has been seen in previous exams. Many students confused it with the idea of solubility and passing through the blood brain barrier which was 1(b) (ii).

This question was reasonably well answered with many students receiving at least one of the two marks.

State one way in which viruses differ from bacteria.

Outline two different ways in which antiviral medications work.

bacteria perform living functions «on their own and viruses do not without host cell»

OR

bacteria have cell walls «and viruses do not»

OR

bacteria do not have a capsid «and viruses do»

OR

bacteria larger than viruses

OR

bacteria reproduce by fission/budding «and viruses reproduce within a living host cell»

OR

bacteria affected by antibiotics «while viruses are not» ✔

Accept “bacteria have flagella/ cytoplasm/ribosome «and virus can have head/protein tail/double stranded RNA/single stranded DNA»”, “asexual reproduction for bacteria”, other specific structural differences between bacteria and viruses, and examples of living functions that bacteria perform (such as excretion, reproduction etc.) that viruses do not.

Any two of:

prevents virus attaching to host cell ✔

alters cell’s genetic material/DNA «so that virus cannot use it to multiply» ✔

blocks enzyme activity in the host cell «so that virus cannot use it to multiply» ✔

prevents removal of protein coat/capsid ✔

prevents injection of viral DNA/RNA into cell ✔

prevents release of «replicated» viruses from host cell ✔

Accept “prevents synthesis of virus by host cell”.

Accept “alters RNA/DNA/genetic material of virus”.

Do not accept just “mimics nucleotides”.

Identify the feature in penicillin responsible for its antibiotic activity.

The widespread use of penicillin and its derivatives has led to the appearance of resistant S. aureus strains.

Outline how these bacteria inactivate the antibiotics.

Outline how the structure of penicillin has been modified to overcome this resistance.

«four-membered» beta-lactam ring  [✔]

Note: Accept a diagram showing a structural representation of the beta-lactam ring.

produce penicillinase/enzyme that deactivates penicillin  [✔]

side-chain changed «preserving beta-lactam ring»  [✔]

Note: Accept “R group changed”.

Most students could identify the beta-lactam ring as the structural feature responsible for penicillin’s activity.

The action of penicillinase/beta-lactamase was less well known with only about a third of students gaining this mark.

Most students were also aware that changing to the side chain of penicillin is often used to counter resistance, though many benefitted from the decision to accept “R-” without any mention of the data booklet structure.

Predict one absorption band present in an infrared (IR) spectrum of aspirin, using section 26 of the data booklet.

Determine the mass of aspirin which reacted with 16.25 cm³ of 0.100 mol dm⁻³ NaOH solution.

Determine the percentage purity of the synthesized aspirin.

Outline how aspirin can be chemically modified to increase its solubility in water.

State why aspirin should not be taken with alcohol.

Outline two factors which must be considered to assess the greenness of any chemical process.

Any one of:
1050–1410 «cm^–1 due to C–O»  [✔]

1700–1750 «cm^–1 due to C=O in acids and esters»  [✔]

2500–3000 «cm^–1 due to O–H in acids»  [✔]

2850–3090 «cm^–1 due to C–H in alkanes and arenes»  [✔]

n(aspirin) «= n(NaOH) = $\frac{\text{16}\text{.25 c}{\text{m}}^3}{1000}$ × 0.100 mol dm^–3 » = 1.625 × 10^–3 «mol»  [✔]

m(aspirin) «= 1.625 × 10^–3 mol × 180.17 g mol^–1 » = 0.293 «g»  [✔]

Note: Award [2] for correct final answer.

« $\frac{\text{0}\text{.293 g}}{0.300\text{ g}}$ × 100% » = 97.7 «%»  [✔]

convert to a salt
OR
react with sodium hydroxide/NaOH  [✔]

Note: Accept other reactions forming soluble salts.

Accept “to ionize” but not “more polar”.

synergistic effect/increased toxicity
OR
increased risk of stomach/intestines bleeding/ulcers/heartburn
OR
increased risk of liver toxicity/damage
OR
increased risk of nausea/vomiting  [✔]

Any two of:
energy requirements «during production»  [✔]

use of toxic materials «during production» [✔]

use of solvents «that are not recycled» [✔]

emission of toxic by-products [✔]

quantity of waste produced
OR
atom economy [✔]

Note: Accept “E-factor/carbon efficiency/% of carbon in reactants vs products” for M1.

Accept references to materials being/not being recycled for M3.

This was a very well answered question. Even weak candidates were able to identify one correct wavenumber.

This was a fairly well answered question with most students receiving both marks and many receiving one mark.

This was a reasonably well answered question but quite a few students still struggled with what should have been a basic calculation, even when using ECF from the previous question.

This question was reasonably answered by most students although some candidates confused the modification of aspirin into an ionic salt with the modification of the side chain of penicillin.

This question was well answered.

This question was not very well answered by some students. Some students gave vague answers or responses not related to the concept of Green chemistry.

Outline one way in which antiviral drugs work.

Discuss two difficulties associated with solving the AIDS problem.

Any one of:
alter cell’s genetic material «so that virus cannot use it to multiply»  [✔]

prevent viruses from multiplying by blocking enzyme activity within host cell
OR
inhibit the synthesis of viral components by blocking enzymes inside the cell [✔]

prevent viruses from entering «host» cell
OR
bind to cellular receptors targeted by viruses
OR
bind to virus-associated proteins/VAPs which target cellular receptors
OR
prevents removal of protein coat/capsid OR prevents injection of viral DNA/RNA into cell [✔]

prevent/hinder the release of viruses from the cell [✔]

Note: Accept “prevents synthesis of virus by host cell”.

Accept “alters RNA/DNA/genetic material of virus”.

Do not accept just “mimics nucleotides”.

Any two of:
viruses lack cell structure «so difficult to target with drugs»  [✔]

HIV is a retrovirus
OR
HIV genetic material is in the form of RNA instead of DNA  [✔]

HIV affects/destroys helper/T-cells which are necessary to fight infection  [✔]

HIV has great genetic diversity so difficult to produce «a» vaccine  [✔]

anti-retroviral agents are expensive so not everyone/country can afford them [✔]

socio-cultural issues deter people from seeking treatment/prevention/diagnosis
OR
lack of education/conversation/stigma associated with being HIV-positive [✔]

mutation of virus/HIV [✔]

virus/HIV metabolism linked to that of host cell [✔]

drugs harm host cell as well as virus/HIV [✔]

HIV difficult to detect/remains dormant [✔]

Candidates responded fairly well to this question. Students who did not receive a mark were either too vague or discussed anti-bacterial methods.

Most candidates were awarded at least one of the two marks possible for this question. Some student responses were too vague or discussed the social and political issues surrounding the AIDS crisis. There were also some responses that did not refer to a virus but AIDS.

Identify the compound responsible for the acidity of gastric juice, and state whether it is a strong or weak acid.

An antacid contains calcium carbonate and magnesium carbonate.

Write the equation for the reaction of magnesium carbonate with excess stomach acid.

Outline how ranitidine reduces stomach acidity.

Calculate the pH of a buffer solution which contains 0.20 mol dm⁻³ ethanoic acid and 0.50 mol dm⁻³ sodium ethanoate. Use section 1 of the data booklet.

pK_a (ethanoic acid) = 4.76

hydrochloric acid/HCl «(aq)» AND strong «acid» ✔

MgCO₃ (s) + 2HCl (aq) → MgCl₂ (aq) + CO₂ (g) + H₂O (l) ✔

NOTE: Accept ionic equation.

blocks/binds to H2-histamine receptors «in cells of stomach lining»
OR
prevents histamine molecules binding to H2-histamine receptors «and triggering acid secretion»
OR
prevents parietal cells from releasing/producing acid ✔

NOTE: Do not accept “antihistamine” by itself.
Accept “H2-receptor antagonist/H2RA” OR “blocks/inhibits action of histamine”.
Accept “blocks receptors in parietal cells «from releasing/producing acid»”.
Do not accept “proton pump/ATPase inhibitor”.

«pK_a = 4.76»
«pH = pK_a + log $\left(\frac{\left[{\text{CH}}_3{\text{COO}}^{-}\right]}{\left[{\text{CH}}_3\text{COOH}\right]}\right)$»
«pH = 4.76 + 0.40 =» 5.16 ✔

State one difference between bacteria and viruses.

Discuss two difficulties, apart from socio-economic factors, associated with finding a cure for AIDS.

The discovery of penicillins contributed to the development of antibiotics.

Explain how the beta-lactam ring is responsible for the antibiotic properties of penicillin. Refer to section 37 of the data booklet.

Any one of:
bacteria perform living functions «on their own and viruses do not without host cell»
OR
bacteria have cell walls «and viruses do not»
OR
bacteria do not have a capsid «and viruses do»
OR
bacteria larger than viruses
OR
bacteria reproduce by fission/budding «and viruses reproduce within a living host cell»
OR
bacteria affected by antibiotics «while viruses are not» ✔

NOTE: Accept “bacteria have flagella/cytoplasm/ribosome «and virus can have head/protein tail/double stranded RNA/single stranded DNA»”

Accept “asexual reproduction” for bacteria.

Accept other specific structural differences between bacteria and viruses, and examples of living functions that bacteria perform (such as excretion, reproduction etc.) that viruses do not.

Accept “bacteria are living and viruses are not”

Any two of:
HIV difficult to detect/remains dormant ✔

HIV mutates rapidly/quickly ✔
NOTE: Do not accept “AIDS mutates” without mention of the HIV/virus.

HIV replicates rapidly/quickly ✔

HIV destroys «T-» helper cells/white blood cells/lymphocytes
OR
HIV attacks immune system ✔

HIV has several «significantly different» strains/subtypes ✔

NOTE: Accept “virus” for “HIV”.
Penalize the use of “AIDS” for “HIV” once only.
Accept “HIV metabolism linked to that of host cell” OR “drugs harm host cell as well as HIV”.

ring is «sterically» strained
OR
angles of 90° instead of 109.5/109/120° angles
OR
angles smaller than 109.5/109/120°/tetrahedral/trigonal planar/triangular planar angle ✔
NOTE: Accept arguments using correct descriptions of hybridization for M1.

ring breaks up/opens/reacts «easily»
OR
amido/amide group «in ring» is «highly» reactive ✔

«irreversibly» binds/bonds to enzyme/transpeptidase
OR
inhibits enzyme/transpeptidase «in bacteria» that produces cell walls
OR
prevents cross-linking of «bacterial» cell walls ✔

NOTE: Do not accept "breaks/binds to cell walls" – a reference to the enzyme is needed for alternatives 1 and 2 for M3.
Do not accept “cell membrane” for “cell wall” for M3.

State the names of two functional groups present in all three molecules, using section 37 of the data booklet.

Explain why diamorphine has greater potency than morphine.

Any two of:
benzene/aromatic ring ✔
«tertiary» amino «group» ✔
ethenylene/1,2-ethenediyl «group» ✔
ether «group» ✔

NOTE: Accept “phenyl” for “benzene ring” although there are no phenyl groups as the benzene ring in this compound is a part of a polycyclic structure.
Do not accept “arene” or “benzene” alone.
Accept “amine” for “amino «group»”.
Accept “alkenyl/alkene/vinylene” for ethenylene/1,2-ethenediyl «group».

Any three of:
morphine has «two» hydroxyl «groups» AND diamorphine has «two» ester/ethanoate/acetate «groups» ✔

NOTE: Accept “heroin” for “diamorphine”.
Accept formulas.
Accept “hydroxy” for “hydroxyl” but not “hydroxide”.
Accept “acyl” for “ester «groups»”.

morphine is more polar than diamorphine
OR
groups in morphine are replaced with less polar/non-polar groups in diamorphine ✔

NOTE: Do not accept just “diamorphine is non-polar” for M2.

morphine is «more» soluble in blood «plasma»
NOTE: Accept “water” for “blood”.
OR
diamorphine is «more» soluble in lipids
NOTE: Accept “fats” for “lipid”.
OR
diamorphine is more soluble in non-polar environment of CNS/central nervous system than morphine ✔

diamorphine crosses the blood–brain barrier/BBB «easily» ✔

Suggest one reactant used to prepare aspirin from salicylic acid.

Aspirin, C₆H₄(OCOCH₃)COOH, is only slightly soluble in water.

Outline, including an equation, how aspirin can be made more water-soluble. Use section 37 in the data booklet.

NOTE: Accept condensed structural formulas.
Accept “ethanoic acid/acetic acid/CH₃COOH”.
Accept “C₄H₆O₃” OR “C₂H₃OCl”.

react with sodium hydroxide/NaOH/«strong» base
OR
convert to «ionic» salt ✔
NOTE: Accept other suitable bases (eg, KOH/NaHCO₃/Na₂CO₃) with corresponding equation for chosen base for M2.
Accept “CaCO₃”, although calcium salicylate is not water soluble.
Accept ionic equation.

C₆H₄(OCOCH₃)COOH (s) + NaOH (aq) → C₆H₄(OCOCH₃)COONa (aq) + H₂O (l) ✔
NOTE: Award [2] for M2.

Outline the impact of antibiotic waste on the environment.

Suggest a concern about the disposal of solvents from drug manufacturing.

«leads to bacterial» resistance «to antibiotics»
OR
destroys useful/beneficial bacteria
OR
useful/beneficial/less harmful bacteria replaced with «more» harmful bacteria ✔

NOTE: Accept "affects/disturbs micro-ecosystems".

Any one of:
«most are» toxic «to living organisms»
OR
incomplete combustion/incineration can produce toxic products/dioxins/phosgene
OR
carcinogenic/can cause cancer ✔

accumulate in groundwater
OR
have limited biodegradability ✔

cost of disposal ✔

NOTE: Do not accept “harmful to the environment”.
Do not accept just “pollutes water”.
Do not accept “hazard of disposal”.
Accept “ozone depletion” only if there is some reference to chlorinated solvents.

Formulate a chemical equation for the neutralization of stomach acid with calcium carbonate.

Calculate the amount, in mol, of stomach acid neutralized by an antacid tablet containing 0.750 g calcium carbonate.

Explain how omeprazole (Prilosec) regulates pH in the stomach.

2HCl(aq) + CaCO₃(s) → H₂O(l) + CO₂(g) + CaCl₂(aq)

Accept ionic equation:

2H⁺(aq) + CO₃^2–(aq) → CO₂(g) + H₂O(l)

[1 mark]

«$\frac{0.750\times 2}{100.09}$ =» 0.0150 «mol HCl»

[1 mark]

inhibits the secretion of stomach acid/H⁺

«active metabolites» bind «irreversibly» to «receptors of the» proton pump

Do not accept “hydrogen/H/H₂” for “H⁺”.

Accept “PPI/proton pump inhibitor” for M2.

Accept “H⁺/K⁺ ATPase” for “proton pump”.

[2 marks]

Compare and contrast the functional groups present in methadone and diamorphine (heroin), giving their names. Use section 37 of the data booklet.

Methadone is sometimes used to help reduce withdrawal symptoms in the treatment of heroin addiction. Outline one withdrawal symptom that an addict may experience.

Similarity:

both contain «at least one» benzene/aromatic ring
OR
both contain amino «group»  

Difference:

diamorphine has one benzene/aromatic ring AND methadone has two phenyl «groups»
OR
diamorphine has one vinylene/ethenylene/1,2-ethenediyl «group» AND methadone has no vinylene/ethenylene/1,2-ethenediyl «group» 
OR
diamorphine has one ether «group» AND methadone has no ether «group»
OR
diamorphine has «two» ethanoate/acetate «groups» AND methadone has no ethanoate/acetate «groups»

Accept “both contain carbonyl «groups»”.
Accept “amine” for “amino «group»”.
Accept “phenyl” for “benzene ring” in M1 and M2 although there are no phenyl groups in diamorphine, as the benzene ring in this compound is a part of a polycyclic structure.
Do not accept “arene” or “benzene” alone in M1 and M2.
Accept “alkenyl/alkene” for “vinylene/ethenylene/1,2-ethenediyl” and “ester” for “ethanoate/acetate”.
Accept “methadone has a ketone/carbonyl AND diamorphine does not/has an ester/ethanoate/acetate”.
Accept “diamorphine is a heterocycle/heterocyclic compound AND methadone is not a heterocycle/heterocyclic compound”.

feeling depressed/anxious/irritable
OR
craving for opioids/heroin
OR
experience fever/cold sweats/nausea/vomiting/insomnia/muscle pain/cramps/diarrhea/increased rate of respiration/increased heartbeat/lacrimation

Accept listed symptoms (eg, depression, anxiety, fever etc.).
Some of the most common symptoms are listed here – there may be other valid ones. Accept “headaches”.

Morphine and diamorphine (heroin) are both opioids.

Explain why diamorphine is more potent than morphine using section 37 of the data booklet.

morphine has hydroxyl/OH groups/is more polar AND diamorphine has ester/ethanoate/acetate groups/is less polar/is lipid soluble

crossing blood brain barrier is easier for non-polar/less polar compounds/for lipid soluble compounds

Accept “alcohol/hydroxy” for “hydroxyl” but not “hydroxide”.

Accept "fats" for "lipid".

[2 marks]

Outline what is meant by low-level waste.

Outline the disposal of LLW.

small/low amounts of radiation AND for a short time  [✔]

Note: Accept “weakly ionizing radiation” instead of “small amounts of radiation”.

Accept “short half-lives” instead of “for a short time”.

stored in shielded containers until radiation drops «to a safe level»  [✔]

Most candidates just listed items that low-level nuclear waste was likely to comprise, rather than giving two of its radiation characteristics (low activity, non-penetrating radiation, short half-life).

There appeared to be very limited awareness of the need to store low-level waste in shielded containers until the radiation falls to a negligible level.