NJC H2 CHEM CM QP

NJC Preliminary Examination 9812/01/17 [Turn over SUBJECT CLASS REGISTRATION NUMBER PHARMACEUTICAL CHEMISTRY Paper 1 Additional Materials: Answer Paper Data Booklet 9812/01 Friday 15 September 2017 2 hours 30 minutes READ THE INSTRUCTIONS FIRST Write your subject class, registration number and name on all the work you hand in. Write in dark blue or black pen. You may use an HB pencil for any diagrams or graphs. Do not use staples, paper clips, highlighters, glue or correction fluid. Answer any five questions. At the end of the examination, fasten all your work securely together. The number of marks is given in brackets [ ] at the end of each question or part question. The use of an approved scientific calculator is expected, where appropriate. You are reminded of the need for clear presentation in your answers. This document consists of 17 printed pages and 1 blank page. NATIONAL JUNIOR COLLEGE SH2 PRELIMINARY EXAMINATION Higher 3 CANDIDATE NAME

2 NJC Preliminary Examination 9812/01/17 1 (a) Analgesic can be classified according to narcotic and non-narcotics analgesics. The following are 4 examples of commonly used analgesics in healthcare. paracetamol aspirin diflunisal codeine (i) Classify these 4 analgesics as narcotic or non–narcotic analgesics. [2] (ii) Outline the different ways narcotic and nonnarcotic analgesics act as pain-killer. [2] (iii) One side effect of prolonged consumption of aspirin is stomach bleeding and ulcers. Describe how aspirin causes stomach bleeding and ulcers. [2] (iv) Paracetamol is an analgesic which is capable of pain relief yet not causing stomach bleeding and ulcers as in the case of aspirin. Suggest two other advantages of using paracetamol over the use of aspirin. [2]

3 NJC Preliminary Examination 9812/01/17 [Turn over Both diflunisal and aspirin inhibit the same enzyme in its mechanism of action to reduce pain. The inhibition effect of these drugs on the target enzymes can be studied using a Michaelis–Menten graph. The higher the rate of enzymatic reactions, the greater the pain level. The inhibition effect of diflunisal against the natural substrate of the target enzyme is as shown below. (v) Suggest the type of inhibition exhibited by diflunisal. Explain your answer. [2] (vi) Copy the graph shown above on your writing paper and draw a graph illustrating the expected inhibition effect of aspirin as compared to that of diflunisal. Explain your answer. [3] (b) (i) Morphine is one of the most effective painkillers that can be extracted from dried juice obtained from unripe seed pods of opium poppy. In order to be effective as an analgesic, the morphine molecule has to pass through the blood brain barrier to dock onto receptors in the brain. Esterases, enzymes that are able to hydrolyse ester linkages but not ether linkages, are found in the brain. Morphine has several functional groups, and a study of structure -activity relationships (SAR) is important in identif ying groups that are important for its activity. morphine Identify the functional groups in morphine that are important for analgesic activity. Suggest the interactions they have at the binding site. [3]

4 NJC Preliminary Examination 9812/01/17 (ii) The activities of 6-acetylmorphine and diamorphine (heroin) compared to morphine are shown in the table below. Drug Structure Analgesia with respect to morphine 6-acetylmorphine 4 x diamorphine 2 x Account as fully as you can the difference in the analgesic activity of diamorphine, 6-acetylmorphine and morphine. [4] [Total: 20]

5 NJC Preliminary Examination 9812/01/17 [Turn over 2 (a) Penicillin G is the naturally occurring penicillin that shows pharmaceutical value. It can be obtained from the mould Penicillium notatum cultured from yeast extract. penicillin G Penicillin G inhibits the transpeptidase enzyme irreversibly through formation of a covalent bond with a serine amino acid residue at the active site. The reaction involves the hydrolysis of the  lactam ring of penicillin G. (i) Suggest the mechanism for the hydrolysis reaction. [3] (ii) Explain how the inhibition described in (a)(i) leads to the death of bacteria. [2] (iii) Suggest why the subsequent hydrolysis by water on the ester group linking the penicillin to the active site does not take place. [1] (iv) Penicillin G can only be administered via injection and not oral means such as pills. Explain why oral administration of penicillin G is ineffective. [2] (b) Methicillin was synthesized in the 1960s to counter the threat of penicillin -resistant strains of Staphylococcus aureus. methicillin (i) Explain the feature of the methicillin molecule which allows it to overcome the

6 NJC Preliminary Examination 9812/01/17 problem of penicillin resistance. [2] (ii) The following structure is an analogue of methicillin. Analogue of methicillin Suggest, with explanation, how you would expect the antibacterial activity of this analogue to compare with that of methicillin. [2] (c) The structures of two other antibiotics, penicillin V and ampicillin, are shown below. These two antibiotics can be administered orally, but not penicillin G and methicillin. penicillin V ampicillin Comment on this difference. Using the structures of the penicillin shown, explain your answer. [3] (d) Ampicillin can cause diarrhoea due to poor absorption through the gut wall. This problem can be overcome by using prodrugs. Talampicillin is an example of such a prodrug. Explain why ampicillin is poorly absorbed and how the prodrug improves the absorption of ampicillin. [2] (e) Outline, with examples, two other ways in which drugs act against bacteria, other than by inhibiting cell wall biosynthesis. [3] [Total: 20]

7 NJC Preliminary Examination 9812/01/17 [Turn over 3 Schiff base is a compound that contains C=N functional group, in which the nitrogen atom is bonded to an alkyl or aryl group. It has the general structure as shown below. The C=N functional group is an analogue of the carbonyl functional group. Schiff base is a common enzymatic intermediate when the enzyme reacts reversibly with a cofactor such as pyridoxal 5’ -phosphate and retinal . It has also been explored for its interesting optoelectronic and gas storage properties. (a) An unknown amino acid, with R group expected to be either –CH3, –CH(CH3)2 or –CH2CH(CH3)2, underwent a condensation reaction with salicylaldehyde to form an amino acid schiff base A, with the expulsion of a water molecule. salicylaldehyde The following data are obtained from the 1H NMR spectrum of Schiff base A. Chemical shift / ppm Splitting Pattern Integral value 1.01 doublet 6 2.20 multiplet 1 3.99 doublet 1 5.00 singlet 1 6.76 – 7.45 multiplet 4 8.13 singlet 1 11.00 singlet 1 (i) Using the 1H NMR data provided, deduce the structure of the unknown amino acid used to make Schiff base A. [4]