GCE. Chemistry. Edexcel Advanced Subsidiary GCE in Chemistry (8CH01) Edexcel Advanced GCE in Chemistry (9CH01) The Pharmaceutical Industry for AS

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1 GCE Chemistry Context study Edexcel Advanced Subsidiary GCE in Chemistry (8CH01) Edexcel Advanced GCE in Chemistry (9CH01) The Pharmaceutical Industry for AS ctober 2007

2 Edexcel, a Pearson company, is the UK s largest awarding body offering academic and vocational qualifications and testing to more than 25,000 schools, colleges, employers and other places of learning here and in over 100 countries worldwide. ur qualifications include GCSE, AS and A Level, GNVQ, NVQ and the BTEC suite of vocational qualifications from entry level to BTEC Higher National Diplomas and Foundation Degrees. We deliver 9.4 million exam scripts each year, with over 3.8 million marked onscreen in As part of Pearson, Edexcel has been able to invest in cutting-edge technology that has revolutionised the examinations system, this includes the ability to provide detailed performance data to teachers. References to third party material made in this specification are made in good faith. Edexcel does not endorse, approve or accept responsibility for the content of materials, which may be subject to change, or any opinions expressed therein. (Material may include textbooks, journals, magazines and other publications and websites.) Authorised by Roger Beard Prepared by Sarah Harrison All the material in this publication is copyright Edexcel Limited 2007

3 Contents Introduction 1 The pharmaceutical industry 3 The use of mass spectroscopy in the labelling of pharmaceutical products and the detection of steroids 3 Carbon nanotubes as vehicles to carry drugs into cells and nanoparticles 4 Choice of solvents in a given context 5 The use of microwaves in the pharmaceutical industry 6 Resources 8

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5 Introduction This document is designed to help teachers to understand the contemporary context of the pharmaceutical industry. It should give teachers information on this context and on how to research it further if they wish. This document could also be given to students as introductory material. Issue 1 ctober 2007 Edexcel Limited

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7 The pharmaceutical industry The use of mass spectroscopy in the labelling of pharmaceutical products and the detection of steroids (Unit 1 topic 1.5c) The use of multiple parallel synthesis (MPS) generates a massive number of compounds, the majority of which will prove to have no value as potential drugs. There is no point wasting time and energy finding the structure of a compound unless it shows potential. The product is purified by high-performance liquid chromatography (HPLC). Industrial systems use replaceable canisters of varying sizes containing a stationary phase chosen to allow separation of the type of compounds produced. The mixture is forced through the system under high pressure. At the top of the column is an analyser, which detects when a solution of a different compound is coming off the top of the column and diverts it to a fresh receiver. In this way the mixture from the synthesis is purified and, if multiple products have been produced, they are separated. Figure 1 HPLC apparatus (on the right) linked to a mass spectrometer (on the left) The products from the HPLC are then characterised by measurement of their molar mass using a mass spectrometer. The unknown compounds are effectively labelled by their molar mass and not by their formula, which is not known at this stage. The mass spectrometer system used is set up so that the molecule tends not to fragment. It may analyse positive or negative ions depending on the groups present. For example, if a molecule has a group that will readily accept a proton then the analysis is of a positive ion, eg amines. In positive ionisation mode, a trace of methanoic acid is often added to aid protonation of the sample molecules; in negative ionisation mode a trace of ammonia solution or a volatile amine is added to aid deprotonation of the sample molecules. Issue 1 ctober 2007 Edexcel Limited

8 Mass spectrometry is also used in the detection of steroid drugs, which are illegal in sport. The sample is passed through a gas chromatogram with the output linked to a mass spectrometer. Mass spectrometry is used because it is very sensitive and can cope with very small concentrations of the drugs. Carbon nanotubes as vehicles to carry drugs into cells and nanoparticles (Unit 2 topic 2.3e) Nanoparticles are currently used in sun lotions containing titanium dioxide nanoparticles that help scatter the Sun s rays. Normal-sized particles would produce opaque creams, but lotions with the nanoparticles are transparent. Plasters containing silver nanoparticles that kill bacteria and squash rackets containing nanotubes for strength are also available. Figure 2 A section of a carbon nanotube (Source: Wikipedia) Various biomedical uses of C 60 derivatives have been proposed, including anti-hiv drugs, bone disorder drugs and antibiotics, but none has yet made an impact on the pharmaceutical world 1. The use of C 60 to transport drugs to the lungs of lung cancer suffers has been proposed. The active molecules are attached to the carbon skeleton and react when they reach the cancer cells. Some research seems to show that water-soluble forms of C 60 are possible and their use has caused some concern since such molecules are claimed to have caused damage to biological tissue, as they may cause the production of oxygen radicals. thers have questioned this research and shown that the molecules can mop up the radicals. In fact, an American company is developing an anti-oxidant drug based on C 60 that should be able to treat diseases that involve tissue damage such as Multiple Sclerosis and Alzheimer s disease 1. There is much information available on the internet and this could provide a source for discussion of the social aspects of How Science Works. 1 Putting the nano into chemistry Chemistry World, December Issue 1 ctober 2007 Edexcel Limited 2007

9 Choice of solvents in a given context (Unit 2 topic 2.5d) If a drug is water soluble it will quickly pass out of the system via the kidneys and into the urine. This may not allow a sufficient concentration to build up for the drug to be effective. If it is not water soluble it will tend to be absorbed into the cell membranes and by fatty tissue. The target in the body for the drug will determine what type of solubility is required and thus solubility is a key factor in drug design. Solubility depends on intermolecular forces. Polar compounds will have groups, such as amine, hydroxyl or carboxyl, attached to them, which can form hydrogen bonds with water or, in some cases, form ion-dipole bonds with metal ions such as sodium. These are hydrophilic groups and the molecules will be soluble in blood, lymph and aqueous tissue. Non-polar groups tend to have long carbon chains or other structural features that mean they do not form hydrogen bonds. These are called lipophilic groups. Aspirin and its related compounds can be used to illustrate several points of chemistry in this area. Aspirin is acetyl salicylic acid. C H C CH 3 Figure 3 Aspirin Aspirin is used as an analgesic (painkiller), an anti-inflammatory drug and as an antipyretic (fever reducer). It is sufficiently soluble in water to be used without modification to its structure to increase solubility. What features of aspirin make it soluble in water? The solubility is not high enough for the drug to be used as a solution: What features of the molecule reduce its solubility in water? The solubility of aspirin is increased by converting the compound to its sodium salt by neutralisation. What type of bonding exists between the acid group and the sodium? How does this increase the solubility? The conversion to the sodium salt does not alter the effectiveness of the drug. Acetyl salicylic acid is such a weak acid that the hydrochloric acid in the stomach regenerates the free acid. C - Na + C CH 3 Figure 4 Sodium acetyl salicylate sodium acetyl salicylate + hydrochloric acid acetyl salicylic acid + sodium chloride Issue 1 ctober 2007 Edexcel Limited

10 The molecule can be further modified to make it fat soluble by making the methyl ester of the acid. H C CH 3 Figure 5 Methyl salicylate Salicylic acid is: H C H Figure 6 Salicylic acid Further study Suggest what reagent would be needed to convert the salicylic acid into its methyl ester and the conditions necessary. Suggest what reagent would be needed to convert the salicylic acid into aspirin and the conditions necessary. The use of microwaves in the pharmaceutical industry (Unit 2 topic 2.13aiv) All chemical reactions go faster at a higher temperature and time wasted on heating is time lost. Experimental research on the use of microwave heaters in chemical laboratories began in the mid 1980s using domestic microwave ovens. The results showed promise but were irreproducible, and the procedure was often dangerous. Modern laboratory microwave heaters are much more powerful and precisely controllable. A reaction that was giving a product after 48 hours using conventional laboratory heating methods, produced an 84 per cent yield in very little time when heated with microwave radiation. Reactions that would need a heavy metal catalyst have been shown to proceed quickly without the catalyst using microwaves. The environmental advantages of not needing a heavy metal are clear. Medicinal chemists are able to carry out reactions in minutes that would have been run overnight. The time and energy-saving advantages are considerable. 6 Issue 1 ctober 2007 Edexcel Limited 2007

11 Figure 7 An industrial microwave heater can heat relatively large volumes of liquids very quickly A domestic microwave is pulsed, unlike the commercial laboratory microwave heaters which are continuous and much more powerful. Microwaves create an electric field, which causes polar molecules such as water or dimethyl sulfoxide (DMS) to try to line up with the field. Before they can line up the field switches to the opposite direction and the molecules try to swivel round and line up in the opposite direction. The microwave energy is effectively changed into thermal energy and the molecules heat those around them. If a mixture is heated in a closed vessel using microwaves it is possible to carry out the reaction at almost twice the boiling point of the solvent. Given that a 10 K rise in temperature can double the rate, the increase in rate over a 60 C rise would be 106 times. Modern microwave heaters can deal with up 1000 cm3 of liquid and can also operate a system under reflux. Issue 1 ctober 2007 Edexcel Limited

12 Resources Chemistry at the Races (Royal Society of Chemistry). This is an excellent resource for illustrating how science is involved in drug detection and shows how chromatography and mass spectroscopy are used in forensic science. Cutting Edge Chemistry (Royal Society of Chemistry). This should be available in most schools and provides useful introduction to the topic of nanotechnology and deals with how the C 60 allotrope of carbon was discovered and the formation of related materials and their properties including nanotubes Inspirational Chemistry Resources for Modern Curricula (Royal Society of Chemistry). This should be available in most schools and provides useful resource materials for use with students. Useful material is available online at: dcd/chemistry/mw.newscientist.html This is an article about microwave chemistry. This example about health and safety could provide a source for discussion. This website gives an excellent account of drugs detection, the problems and the techniques involved. 1572rl191007S:\LT\PD\SUPPRT\GCE in Chemistry Pharma Industry AS CS.doc.1-13/0 8 Issue 1 ctober 2007 Edexcel Limited 2007

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