Chemistry in use book 2 context 7

CONTEXT 7 NEW MATERIALS 1
CONTEXT 7
TOP SEVEN DRUGS OF THE TWENTY-FIRST CENTURYAlthough in the New Materials context the focus was on plastics and polymers, they are not the only substances chemists have synthesised to improve our quality of life. Another major chemical development is pharmaceutical drugs. The active ingredients in many medicines—the drugs—have been and continue to be derived from natural sources. For example, salicylic acid is found in willow bark and today is synthesised to produce aspirin.
The magnifi cent seven—magic bullets of the twenty-fi rst centuryby Andrew Parsons Signifi cant progress has been made in pharmaceutical research since Paul Ehrlich fi rst predicted (in 1906) that chemicals made in the laboratory could act as ‘magic bullets’, which could seek out and destroy disease-causing agents. Today, a typical pharmacy will stock around 2000 medicines, the majority of which contain a single organic molecule as the active ingredient. In 2001, worldwide sales of pharmaceuticals totalled more than $364 billion (more than £200 000 million), and at the top of the pile were the seven blockbusters shown below. These organic molecules work in different ways to treat a range of important diseases but, as in the fi lm The Magnifi cent Seven, these magnifi cent seven are constantly in danger of being shot down. The desire for new and improved medicines is unrelenting and so the average lifetime of these drug molecules is only 15–20 years.
This drug is currently prescribed to more than 18 million people with high cholesterol levels. In 2001, sales of Lipitor® amounted to a staggering $7.0 billion (£4000 million), making it the number one selling medicine. The high demand for this drug refl ects the fact that one in fi ve of us has a high level of cholesterol. Lipitor® works by reducing the amount of cholesterol in the body by inhibiting its production in the liver. Lipitor® Copyright 2006 McGraw-Hill Australia. Permission is granted to reproduce for classroom use.
CONTEXT 7 NEW MATERIALS 2
lowers the overall amount of cholesterol in the blood as well as LDL (low-density lipoprotein) cholesterol. LDL cholesterol is known as ‘bad’ cholesterol because it is believed to be responsible for the development of coronary heart disease. Lowering LDL cholesterol levels can therefore reduce the incidence of coronary heart disease, which is among the biggest killers in the UK.
Prilosec® or Losec® (Astra Merck Inc.) Prilosec® is commonly used to treat diseases that are related to excess acid in the stomach, including ulcers are mainly caused by a bacterial infection. This weakens the coating of the stomach, allowing acid and bacteria to get to the sensitive lining underneath, which can cause a sore or hole (known as a peptic ulcer). Prilosec® is an example of a ‘proton-pump inhibitor’. It works by blocking certain cells in the stomach that control the production of acid.
Zocor®, like Lipitor®, is a drug that reduces the amount of cholesterol in the blood. It inhibits the activity of an enzyme that regulates the body’s ability to produce cholesterol. In one study in Scandinavia, this drug was shown to reduce the level of total cholesterol in patients by 25% and LDL cholesterol by 35%. High levels of cholesterol in the bloodstream can restrict the fl ow of blood, which can cause a heart attack or stroke.
This medicine is used to treat high blood pressure (or hypertension) and angina (a type of chest pain due to an inadequate blood supply to the heart). High blood pressure can occur when blood vessels become too narrow and/or stiff and this can lead to a heart attack, stroke or kidney disease. Norvasc® is an example of a long-acting calcium channel blocker, which prevents the fl ow of calcium ions into the muscle cells of blood vessels This causes the blood vessels to widen and relax, allowing blood to fl ow more easily around the body and so lowering blood pressure.
Like Losec®, Prevacid® is a proton-pump inhibitor that works by decreasing the amount of acid produced in the stomach. It does this by blocking the enzyme system responsible for acid secretion and is used to treat and prevent stomach and intestinal ulcers.
Zyprexa® is an antipsychotic agent, which is prescribed in the treatment of schizophrenia and bipolar mania. It is thought to work by adjusting the imbalance of chemicals (including serotonin and dopamine) in the brain, which may cause hallucinations, delusions and confusion. By doing so, it can help to restore normal thinking and mood. Since its approval in 1996, it has been prescribed for more than 11 million people in 84 countries.
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CONTEXT 7 NEW MATERIALS 3
This medicine, like aspirin, is an example of a non-steroidal anti-infl ammatory drug (NSAID). It is used to reduce pain, infl ammation (swelling/soreness) and stiffness caused by osteoarthritis and rheumatoid arthritis. Celebrex® works by selectively inhibiting the action of an enzyme called COX-2, which plays a key role in pain and infl ammation.
Even though these molecules have different medicinal properties it is interesting to see that they all contain at least one heterocycle. Heterocycles are rings that have one or more oxygen or nitrogen atoms as part of the ring. Six of the compounds also contain aromatic rings, including substituted benzene rings. Therefore, to be a successful medicinal chemist, it is important to have a good understanding of the preparation, structure and properties of aromatic and heterocyclic molecules.
Chemistry Review Vol. 14 No. 1 (Sept 2003, pp. 12–13) ASPIRINThe active ingredients of medicines are drugs—substances that alter the way your body works. A medicine prevents things getting worse when your body is working wrongly and can help bring about a cure, for example when you take aspirin or antibiotics. Not all drugs are medicines. Alcohol and nicotine are drugs, but they are certainly not medicines.
The study of drugs and their actions is called pharmacology. Today’s medicines are designed to have specifi c effects. Originally medicines were drawn directly from nature and their effectiveness was discovered by trial and error. Aspirin is a good example of this.
Back in the Middle Ages people would be given a concoction of willow bark extract to drink to reduce pain and fever. Willow bark contains a chemical called salicin, which is converted to salicylic acid in the body. Salicylic acid is one of many compounds that act as a non-steroidal anti-infl ammatory drug (NSAID); however, it is extremely irritating to the stomach and mucous membranes.
In 1897 a German chemist working for Bayer named Felix Hoffmann found that when he replaced the hydrogen on the — OH group with — C(O)CH , as shown in the equation below, the drug was much more tolerable to the stomach.
The Bayer company quickly marketed the drug under the trade name ‘Aspirin’.
The presence and properties of functional groups are responsible for the action of all drugs. Looking at the structure of aspirin above you can see it has three sub-units—a benzene ring, which makes aspirin soluble in fatty compounds, a — COOH group, which is carboxylic acid group and a — O — C(O) — CH group, which is an ester. The acid and ester groups are responsible for the drug activity.
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Aspirin has a K of 3.2 × 10–4, which means it is only weakly ionised in water. In acidic conditions of the stomach the extent of ionisation is even less, so this ensures most of it remains in the unionised form, which is virtually insoluble in water but soluble in lipids (fats). In this form it is easily absorbed and distributed around the body.
relief scene are acetaminophen, the active naproxen. The last two drugs have been found to be as effective as aspirin and less irritating to Drugs with similar physiological properties often have similar molecular structures, including All contain a benzene ring with two substituents, but the substituents differ in detail.
How aspirin worksAlthough the nervous system carries messages through the body by electrical impulses, most of the body’s messages are conveyed through chemical processes. The chemical messengers are hormones, which are produced in the body’s endocrine glands.
Aspirin and other drugs that are physiologically active are almost always involved in altering the body’s chemical communication system, which is very complex. The versatility of aspirin and other NSAIDs is related to their ability to block the actions of other molecules.
In the body the aspirin molecule is hydrolysed to acetic acid and the active Research on the activity of aspirin indicates that one of its modes of action involves blocking cyclooxygenase (COX) enzymes. These enzymes are biological catalysts that synthesise a series of compounds called prostaglandins. Prostaglandins are extremely powerful chemicals and act effectively in low concentrations. They are involved in pain infl ammation (swelling), fever, blood pressure regulation, menstrual cramps, labour, blood-clotting and asthma attacks.
By blocking the action of the cyclooxygenase (COX) enzyme, aspirin prevents the formation of prostaglandins, reducing fever and swelling. It also suppresses pain receptors and so acts as a painkiller and makes the blood-clotting mechanism less effective because clotting is controlled by two prostaglandins. This is sometimes incorrectly referred to as ‘thinning the blood’. This is how aspirin helps protect those with heart disease from heart attacks.
After a few hours the salicylic acid breaks down to highly soluble chemicals, which Ibuprofen is better than aspirin at blocking the action of the cyclooxygenase (COX) enzyme, so it is more effective at pain relief and fever reduction.
People who are allergic to aspirin may take non-aspirin pain relievers such as acetaminophen. Although this drug is effective for relieving pain and fevers, it does not help with infl ammation or reducing blood-clotting. This is because it inhibits a different enzyme rather than cyclooxygenase (COX).
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Although aspirin is a specifi c chemical—acetylsalicylic acid—not all aspirin tablets are the same. Although all tablets contain the aspirin molecule, they are also composed of mixtures of other components, including inert fi llers and bonding agents that hold the tablet together. Buffered aspirin tablets also include weak bases to counteract the natural acidity of aspirin. The differences in formulation can infl uence how fast the drug acts and the extent of stomach irritation. Aspirin also decomposes over time, so notice should be taken of use-by dates.
SHATTERPROOF GLASSShatterproof glass is not really glass at all—it is actually a plastic. Shatterproof windows are made of a thermoset plastic called bisphenol-A polycarbonate.
Polycarbonate is a generic term for the long-chain linear polyester that is composed of alternating units of carbonate group (from carbonic acid, H CO ) and an aromatic alcohol known as a phenol, which possesses two — OH groups.
bisphenol-A, which has the structure shown here.
Before the polymerisation reaction can occur, the monomer is reacted with sodium hydroxide to obtain the sodium salt of bisphenol-A. This sodium salt is then reacted with a carbonyl chloride to produce the polycarbonate as shown in the following reaction: The molecular stiffness of the polycarbonate is due to the rigid phenyl groups on the molecular chain and the two methyl side-groups. The transparency of the material arises from the non-crystalline nature of the polymer due to the intermolecular attraction between phenyl groups in neighbouring chains and the rigidity of the chains.
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CONTEXT 7 NEW MATERIALS 6
Another polymer used to make unbreakable windows is poly(methyl methacrylate) (acrylic) or PMMA. This is a vinyl polymer made from the monomer methyl methacrylate according to the reaction: A Florida-based company has developed a product called OneWay® bulletproof glass by combining polycarbonate, acrylic and glass layers. The glass is being installed in police vehicles in New Orleans. The special material offers bullet resistance from criminals on the outside, while allowing police offi cers to return fi re from the inside of the vehicle in a hostile situation.
The outside layer is acrylic which, although brittle, is strong when compressed; the inside layer is polycarbonate which can stretch, absorbing the energy of the bullet’s impact, thus stopping it from penetrating the window. The two polymer layers are separated by a glass layer and all three layers are fused together during a secret manufacturing process involving special glue or resin.
Bullets fi red from the inside can penetrate the glass because the polycarbonate layer is compressed while the acrylic layer is stretched and weakened, so it shatters. The heat from the bullet closes up the hole so the glass is even self-healing.
As well as being used in police vehicles there are many other possible applications. These include shops, banks, military checkpoints, prisons and even private homes. The glass has been extensively tested in laboratories in the United States of America and the Middle East. It has shown to be able to resist intense heat and humidity, and has passed bomb-blast survivability tests so it also has considerable appeal for military purposes.
MEDICINESChemistry plays an important part in modern medicine. Thanks to the efforts of organic chemists it is possible to design the right molecule for curing an illness and/or relieving its symptoms. The active ingredients of medicines are drugs—substances that alter the way your body works.
Pain-killing drugsPainkillers such as aspirin, paracetamol and ibuprofen are commonplace. Aspirin and ibuprofen work by inhibiting the production of chemicals that cause infl ammation.
If you want to know more about how these chemicals work, read the section on AntibioticsAntibacterial chemicals are the main antibiotics used for the treatment of infectious diseases caused by bacteria invading the body. With most diseases our body’s own defences can cope perfectly well by producing chemicals to kill the invading bacteria. Copyright 2006 McGraw-Hill Australia. Permission is granted to reproduce for classroom use.
CONTEXT 7 NEW MATERIALS 7
Occasionally, however, the system fails and we need to take medicines to destroy a disease-causing micro-organism.
In the mid-nineteenth century it was common for patients to die from infections contracted during a variety of medical procedures, most notably during childbirth. This is because people were regularly infected by their own doctors who did not wash their hands. In 1847, a Viennese doctor, Ignaz Semmelweiss, recommended that doctors wash in a chloride of lime solution after performing autopsies, and wash with soap and water between patient visits. With these simple improvements in medical practices, hospital mortality rates declined dramatically. Today, thanks to modern antiseptic and antibacterial products, the risk of surgery-related infections has been reduced dramatically.
In the past, many medicines were based on poisonous elements such as mercury, arsenic and bismuth. Many bismuth compounds were found to be highly effective antibacterials for syphilis, as was the chemical arsphenamine (the structure of which is below).
The discovery of penicillin was a major breakthrough in the production of antibiotic chemicals. The early penicillins were natural chemicals from fungi, but later chemists discovered how to make semi-synthetic ones. This paved the way for large-scale drug production.
Some penicillin are quite unstable under acidic conditions and react with stomach acid to lose their antibiotic activity, so these have to be administered by injection. Research chemists found that the active component in penicillin molecules is also found in other types of molecules (not penicillins) that kill bacteria. Further research has shown these antibacterials work by inhibiting the synthesis of bacterial cell walls.
Sulfonamides are another group of chemicals found to be successful in fi ghting diseases. Because these molecules are relatively simple and easy to make a large range has been made and tested. This has resulted in many new antibacterials becoming available. Research into how these chemicals work showed they inhibit nucleic acid synthesis in bacteria. Unfortunately many bacteria have evolved to be resistant to sulfonamides, so these drugs are becoming less effective and their use is in decline.
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Creepy-crawliesInsects, in particular lice, are easily spread from person to person. These insects become residents in the hair and can be diffi cult to get rid of. One option is to shave the hair, but most people prefer to use a chemical treatment.
A synthetic chemical developed for use as an agricultural chemical, Malathion, has been found effective on humans too. It is an organophosphate molecule, which was developed from the warfare gas sarin.
Mind moleculesMental illness is due to changes in the regular chemical reactions required by the brain cells. Depression is the most common of mental disorders and comes about because the regular chemistry of the brain gets out of balance. The use of man-made chemicals has been highly successful in the treatment of this disorder.
Tricyclic antidepressants (TCAs) are important molecules in the treatment of depression and one of the more common is amitriptyline (its structure is shown here). This molecule is tricyclic because it contains two benzene rings joined by a cycloheptadiene ring to give a dibenzocycloheptadiene molecule.
Lithium is also a well-established treatment for certain types of depression, such as manic depression (also known as bipolar disorder). Lithium carbonate (Li CO ) in a pill form reacts with the hydrochloric acid in the stomach in an acid–carbonate reaction to release lithium ions, which are absorbed into the bloodstream and carried to the brain. Because lithium is a toxic chemical it is important to monitor the blood lithium content of the patient to ensure it is within safe levels.
Chemists continue to strive to develop more effective, safe medicines to prolong our lives and improve their quality.
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CONTEXT 7 NEW MATERIALS 9
POLYMERS
www.mdl.com/downloads/downloadable/
(A website that allows a molecular modelling program called CHIME to be downloaded free)
www.pslc.ws/macrog/maindir.htm
(A comprehensive website with an enormous amount of information about plastics and polymers. It is organised
into a number of levels. Level 1 is organised as a series of shops, which give the uses of most polymers. Level 2
provides detailed information about specifi c polymers, while Level 3 gives the structure and properties. Level 4
provides information about making the polymers, including reactions, and Level 5 is all about the ways polymer
scientists analyse polymers.)
www.pslc.ws/ret2003/cover.html
(This website provides information on polymers and polymer coatings, with procedures for laboratory activities to
test various properties of polymers.)
www.pslc.ws/polydel/index.htm
(A website that provides lots of information on different polymers and their uses.)
http://homepages.enterprise.net/caistorg/Main_p.html
(This website explains the processes used in industry to manufacture practically any plastic product.)
www.science.org.au/nova/061/061key.htm
(Information on biodegradable plastics from the Australian Academy of Science.)
www.beyonddiscovery.org/content/view.article.asp?a=203
(Website from the National Academy of Sciences (USA), which provides a history of polymer development with
some good links to further information.)
www.kcpc.usyd.edu.au/discovery/Syllabus.html
(Resources on polymers prepared for the New South Wales HSC by the Key Centre for Polymer Colloids. Good
information on types of polymerisation and replacing natural products.)
www.pacia.org.au/
(Website of the Plastics and Chemicals Industry Association. Click on Education to obtain information on plastics
in sport, the plastics industry and chemical fact sheets or click on Recycling to obtain information on facts about
plastics and recycling.)
www.plasticsresource.com/s_plasticsresource/index.asp
(The American Plastics Council provides some information of how plastics are made and recycling.)
www.bpf.co.uk/bpfi ndustry/An_Introduction_to_Plastics.cfm
(Information on plastics by the British Plastics Federation.)
www.plasticsusa.com/matchar.html
(Plastics USA provides information on the properties of most major plastics.)
www.ides.com/x5/register/default.aspx?cmp=401&OVRAW=density%20of%20plastics&OVKEY=
plastic%20density&OVMTC=standard
(A website that provides free plastics data sheets. You must create an account, but this is free.)
PLASTICS RECYCLING
www.visy.com.au/divisions/index.aspx?did=1
(Click on Education, then plastics to fi nd out about plastic recycling in Australia.)
www.visyrecycling.com.au/images/pdf/body/Plastics_ID.doc
(Information on plastics ID codes and uses of original and recycled plastic.)
http://scifun.chem.wisc.edu/chemweek/POLYMERS/Polymers.html
(Fact sheet about plastics recycling groups.)
Copyright 2006 McGraw-Hill Australia. Permission is granted to reproduce for classroom use.
CONTEXT 7 NEW MATERIALS 10
www.pacia.org.au/
(Website of the Plastics and Chemicals Industry Association. Click on Recycling to obtain information on facts
about plastics and recycling.)
www.plasticsresource.com/s_plasticsresource/index.asp
(American Plastics Council provides some information of how plastics are made and recycling.)
MOLECULAR MODELLING
www.chem.ox.ac.uk/course/cache/default.html
(Molecular modelling tutorial)
www.wellesley.edu/Chemistry/Flick/molecules/newlist.html
(Alphabetic list of molecular structures.)
www.umass.edu/microbio/chime/
(Molecular structures.)
http://publications.nigms.nih.gov/medbydesign/
(Information describing how medicines are designed.)
Copyright 2006 McGraw-Hill Australia. Permission is granted to reproduce for classroom use.

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