Chemistry • Year 12 • Module 8 • Lesson 11
Drug Classification & Functional Groups
Apply drug classification and functional group reasoning to real data, current Australian context and structure–activity scenarios.
1. Drug–functional group data table interpretation
The table below summarises six common drugs, their therapeutic classification, key functional groups, and one consequence of those groups. Study the table and answer the questions that follow. 8 marks
| Drug | Therapeutic class | Key functional groups | Chemical consequence |
|---|---|---|---|
| Aspirin | Analgesic / anti-inflammatory (NSAID) | Carboxylic acid (−COOH), ester (−COO−), aromatic ring | Weakly acidic; ester linkage is hydrolysable in aqueous conditions |
| Paracetamol | Analgesic / antipyretic | Phenol (−OH on aromatic ring), amide (−CONH−), aromatic ring | More polar than ibuprofen; strong hydrogen bonding capacity |
| Ibuprofen | Analgesic / anti-inflammatory (NSAID) | Carboxylic acid (−COOH), aromatic ring, branched alkyl chain | Weakly acidic; significant non-polar hydrocarbon region → mixed polarity |
| Penicillin G | Antibiotic (β-lactam) | Amide (−CONH−), carboxylic acid (−COOH), thioether, β-lactam ring | β-lactam ring is highly reactive; central to antibacterial mechanism |
| Amoxicillin | Antibiotic (β-lactam) | Amine (−NH2), amide (−CONH−), carboxylic acid (−COOH), β-lactam ring | More polar than penicillin G; broader spectrum; wider oral bioavailability |
| Morphine | Opioid analgesic | Phenol (−OH on aromatic ring), amine (−N), ether (−O−), aromatic ring | Tertiary amine → basic character; phenol → H-bonding with opioid receptor |
1.1 Identify the two drugs in the table that share the greatest structural similarity in terms of functional groups. Give one piece of evidence from the table. 2 marks
1.2 Using data from the table, explain why ibuprofen has “mixed polarity” while paracetamol does not share this description. 3 marks
1.3 Predict which drug in the table would be most susceptible to chemical hydrolysis in the stomach’s acidic aqueous environment, and justify your prediction with reference to a specific functional group. 3 marks
2. Cause-and-effect chain — how a functional group change alters drug properties
A medicinal chemist modifies ibuprofen by replacing its −COOH group with an −OH group (a simple alcohol). Trace the chain of consequences that follows from this structural change, completing each effect box. 6 marks
Overall outcome (so…): Why might this modified molecule no longer be effective as an anti-inflammatory analgesic?
3. Graph interpretation — Australian OTC painkiller sales volume
The figure below shows estimated annual retail sales volume (millions of standard packs) for the four most commonly purchased over-the-counter (OTC) analgesics in Australia, averaged over 2019–2022. Data are drawn from publicly available Pharmaceutical Benefits Scheme (PBS) and IBISWorld retail pharmacy industry estimates. 8 marks
Estimated Australian OTC analgesic retail sales 2019–2022 average (millions of standard packs). Source: IBISWorld Retail Pharmacy in Australia industry report; PBS open data (adapted and estimated for illustrative purposes).
3.1 Describe the overall pattern in the data. Which two drugs dominate Australian OTC analgesic sales, and by approximately what factor does the leading drug exceed the third-placed drug? 2 marks
3.2 A student claims that paracetamol outsells ibuprofen mainly because its tablet dose (500 mg) is larger than ibuprofen’s (200 mg), so each pack “gives more medicine.” Evaluate this claim with reference to functional groups and pharmacophore. 3 marks
3.3 Aspirin and ibuprofen are both NSAIDs (non-steroidal anti-inflammatory drugs) containing a −COOH group, yet aspirin’s sales are well below ibuprofen’s. Suggest one structural or pharmacological reason why two drugs with the same key functional group might still have different sales volumes. 3 marks
4. Case study — CSL Broadmeadows and Australian pharmaceutical manufacturing
Read the passage, then answer the question. 5 marks
CSL Limited’s Broadmeadows facility in Victoria is historically Australia’s largest pharmaceutical manufacturing site. For decades it was a key producer of aspirin tablets at scale. Aspirin (acetylsalicylic acid, molecular formula C9H8O4) must be synthesised from salicylic acid and acetic anhydride via an esterification reaction, forming the ester linkage that is characteristic of its structure. Before aspirin can be sold on the Australian market, CSL must hold a Manufacturing Licence and the product must be entered on the Australian Register of Therapeutic Goods (ARTG), administered by the TGA. Once registered, a medicine may be recommended to the Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the PBS so that the government co-pays part of the cost for patients.
Q4. Using the passage and your lesson knowledge, explain how the ester functional group in aspirin arises in synthesis, what chemical property it confers on the molecule, and why the TGA and PBS systems matter to Australian patients who wish to purchase aspirin affordably. In your answer, identify at least two functional groups present in aspirin and link one to its chemical behaviour. 5 marks
Q1.1 — Most similar functional group profiles
Aspirin and ibuprofen are the two drugs that share the greatest structural similarity in terms of functional groups — both contain a carboxylic acid (−COOH) group and an aromatic ring, and neither contains an amide or phenol. Evidence: the table lists −COOH and aromatic ring for both under “Key functional groups”. [1 mark for correct pair; 1 mark for table evidence.]
Q1.2 — Mixed polarity of ibuprofen vs paracetamol
Ibuprofen has “mixed polarity” because it contains a polar carboxylic acid group alongside a large branched alkyl chain (non-polar hydrocarbon region) [1]. The hydrocarbon region contributes significant non-polar character, so the molecule has both polar and non-polar domains [1]. Paracetamol has a phenol and an amide — both polar and capable of hydrogen bonding — without a large non-polar alkyl region, so its overall character is more uniformly polar [1].
Q1.3 — Hydrolysis prediction
Aspirin is most susceptible to hydrolysis [1]. The ester linkage (−COO−) in aspirin is hydrolysable in aqueous acidic conditions (such as the stomach), cleaving to regenerate salicylic acid and acetic acid [1]. Esters are noted in the table as “hydrolysable in aqueous conditions”, and no other drug in the table contains an ester group [1].
Q2 — Cause-and-effect chain
Effect 1: The modified molecule loses acidic character — a simple −OH alcohol is not as acidic as −COOH (pKa alcohol >> pKa carboxylic acid), so the molecule no longer ionises significantly at physiological pH.
Effect 2: Aqueous solubility at physiological pH is reduced or altered — −COOH can ionise to carboxylate (−COO−), which is very water-soluble; a neutral −OH does not ionise in the same way, so solubility may decrease depending on pH.
Effect 3: The pharmacophore changes — the carboxylic acid group in ibuprofen is part of the interaction pattern that inhibits the COX enzyme; replacing it with an alcohol alters the hydrogen-bonding and ionic interactions at the active site, likely reducing binding affinity.
Overall outcome: Because the pharmacophore is altered (loss of ionisable −COOH, reduced aqueous solubility, weaker enzyme binding), the modified molecule would likely be a much less effective anti-inflammatory analgesic or completely inactive.
Q3.1 — Overall pattern
Paracetamol and ibuprofen dominate Australian OTC analgesic sales. Paracetamol leads at approximately 38 million packs; the third-placed drug (aspirin at 9.1 million) is outsold by paracetamol by a factor of approximately 4:1 (38.1 ÷ 9.1 ≈ 4.2). [1 mark for identifying the two leaders; 1 mark for a numerically supported comparison.]
Q3.2 — Student claim evaluation
The student’s claim is not well supported [1]. Different tablet masses reflect differences in pharmacological potency, not simply the amount of “medicine” delivered [1]. Paracetamol and ibuprofen have different functional groups (paracetamol: phenol + amide; ibuprofen: carboxylic acid + alkyl chain), leading to different pharmacophore geometries and different interactions with their respective molecular targets. A 200 mg ibuprofen dose can be therapeutically equivalent or superior for inflammation to 500 mg paracetamol precisely because potency is a function of structure, not tablet mass [1].
Q3.3 — Same functional group, different sales
Accept any chemically valid reason. Model answer: aspirin also contains an ester group that is hydrolysed in the stomach and intestine to salicylic acid, which causes gastric irritation in some patients; this has reduced clinical preference for aspirin in general pain relief relative to ibuprofen [1]. Additionally, aspirin is used at low dose for cardiovascular protection (a distinct pharmacological use from pain relief) which drives some of its sales into a different market segment [1]. The overall molecular framework beyond the shared −COOH pharmacophore — aspirin’s acetyl group vs ibuprofen’s branched chain — produces different binding characteristics and side-effect profiles, influencing prescribing and purchasing patterns [1].
Q4 — CSL, aspirin and Australian drug regulation
Marking criteria (5 marks): [1] Ester in aspirin arises from esterification — salicylic acid’s phenolic −OH reacts with acetic anhydride, forming the −COO− ester linkage. [1] At least two functional groups correctly identified: ester (−COO−) and carboxylic acid (−COOH) are both present in aspirin. [1] Chemical property linked to one group: −COOH gives aspirin its weak acidity (it can donate H+); ester is hydrolysable in aqueous acid, which is why aspirin can break down in the stomach. [1] TGA role: before aspirin can be sold in Australia, CSL must register it on the ARTG; the TGA evaluates safety, quality and efficacy before registration is granted. [1] PBS/PBAC role: once registered, the PBAC can recommend aspirin for listing on the PBS, enabling the government to subsidise part of the purchase price for eligible patients, making it more affordable. Accept equivalent accurate responses.