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Option D - Medicinal Chemistry

D.1 Pharmaceutical products and drug action

Essential idea: Medicines and drugs have a variety of different effects on the functioning of the body.

Nature of science:
Risks and benefits—medicines and drugs go through a variety of tests to determine their effectiveness and safety before they are made commercially available. Pharmaceutical products are classified for their use and abuse potential. (4.8)


Understandings:
• In animal studies, the therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50).
• In humans, the therapeutic index is the toxic dose of a drug for 50% of the population (TD50) divided by the minimum effective dose for 50% of the
population (ED50).
• The therapeutic window is the range of dosages between the minimum amounts of the drug that produce the desired effect and a medically
unacceptable adverse effect.
• Dosage, tolerance, addiction and side effects are considerations of drug administration.
• Bioavailability is the fraction of the administered dosage that reaches the target part of the human body.
• The main steps in the development of synthetic drugs include identifying the need and structure, synthesis, yield and extraction.
• Drug–receptor interactions are based on the structure of the drug and the site of activity.

Applications and skills:
• Discussion of experimental foundations for therapeutic index and therapeutic window through both animal and human studies.
• Discussion of drug administration methods.
• Comparison of how functional groups, polarity and medicinal administration can affect bioavailability.

Guidance
For ethical and economic reasons, animal and human tests of drugs (for LD50/ED50 and TD50/ED50 respectively) should be kept to a minimum.

International-mindedness:
• In some countries certain drugs are only available with prescription while in
other countries these same drugs are available over the counter.

Theory of knowledge:
The same drug can be identified by different names. Are names simply labels or do they influence our other ways of knowing?
• Drugs trials use double blind tests. When is it ethically acceptable to deceive people?
• All drugs carry risks as well as benefits. Who should ultimately be responsible for assessing these?
Public bodies can protect the individual but also limit their freedom. How do we know what is best for society and the individual?

Aims
Aim 9: There have been advances in the development of pharmaceuticals, but there are many limitations to their impact and reach.
• Aim 10: The development of new medicines is often done in collaboration with biologists and physicists.

D.2 Aspirin and penicillin

Essential idea: Natural products with useful medicinal properties can be chemically altered to produce more potent or safer medicines.

Nature of science:
Serendipity and scientific discovery—the discovery of penicillin by Sir Alexander Fleming. (1.4)
Making observations and replication of data—many drugs need to be isolated, identified and modified from natural sources. For example, salicylic acid from bark of willow tree for relief of pain and fever. (1.8)

Understandings:

Aspirin:
• Mild analgesics function by intercepting the pain stimulus at the source, often by interfering with the production of substances that cause pain, swelling or fever.
• Aspirin is prepared from salicylic acid.
• Aspirin can be used as an anticoagulant, in prevention of the recurrence of heart attacks and strokes and as a prophylactic.

Penicillin:
• Penicillins are antibiotics produced by fungi.
• A beta-lactam ring is a part of the core structure of penicillins.
• Some antibiotics work by preventing cross-linking of the bacterial cell walls.
• Modifying the side-chain results in penicillins that are more resistant to the penicillinase enzyme.

Applications and skills:

Aspirin
• Description of the use of salicylic acid and its derivatives as mild analgesics.
• Explanation of the synthesis of aspirin from salicylic acid, including yield, purity by recrystallization and characterization using IR and melting point.
• Discussion of the synergistic effects of aspirin with alcohol.
• Discussion of how the aspirin can be chemically modified into a salt to increase its aqueous solubility and how this facilitates its bioavailability.

Penicillin
• Discussion of the effects of chemically modifying the side-chain of penicillins.
• Discussion of the importance of patient compliance and the effects of the overprescription of penicillin.
• Explanation of the importance of the beta-lactam ring on the action of penicillin.

Guidance:
• Students should be aware of the ability of acidic (carboxylic) and basic (amino) groups to form ionic salts, for example soluble aspirin.
• Structures of aspirin and penicillin are available in the data booklet in section 37

International-mindedness:
• Aspirin is used in many different ways across the globe.
• The first antibacterial changed the way that disease was treated across the globe.

Theory of knowledge
Different painkillers act in different ways. How do we perceive pain, and how are our perceptions influenced by the other ways of knowing?
• “Chance favours only the prepared mind.” (Louis Pasteur). Fleming’s discovery of penicillin is often described as serendipitous but the significance of his observations would have been missed by non-experts. What influence does an open-minded attitude have on our perceptions?

 

Syllabus and cross-curricular links:
Topic 1.3—yield of reaction
Topic 10.2—functional groups
Biology topic 6.3—defence against infectious disease

Aims:
Aim 6: Experiments could include the synthesis of aspirin.
• Aim 8: Discuss the use/overuse of antibiotics for animals.


D.3 Opiates

Essential idea: Potent medical drugs prepared by chemical modification of natural products can be addictive and become substances of abuse.

Nature of science:
Data and its subsequent relationships—opium and its many derivatives have been used as a painkiller in a variety of forms for thousands of years. One of these derivatives is diamorphine. (3.1)

Understandings:
The ability of a drug to cross the blood–brain barrier depends on its chemical structure and solubility in water and lipids.
• Opiates are natural narcotic analgesics that are derived from the opium poppy.
• Morphine and codeine are used as strong analgesics. Strong analgesics work by temporarily bonding to receptor sites in the brain, preventing the transmission of pain impulses without depressing the central nervous system.
• Medical use and addictive properties of opiate compounds are related to the presence of opioid receptors in the brain.

Applications and skills:
Explanation of the synthesis of codeine and diamorphine from morphine.
• Description and explanation of the use of strong analgesics.
• Comparison of the structures of morphine, codeine and diamorphine (heroin).
• Discussion of the advantages and disadvantages of using morphine and its derivatives as strong analgesics.
• Discussion of side effects and addiction to opiate compounds.
• Explanation of the increased potency of diamorphine compared to morphine based on their chemical structure and solubility.

Guidance:
• Structures of morphine, codeine and diamorphine can be found in the data booklet in section 37.

International-mindedness:
• Many illegal drugs are cultivated or produced in a small number of countries and then sold and distributed globally. Cultural and economic viewpoints differ on the production and sale of opiates around the world.

Theory of knowledge:
• Cultures often clash over different perspectives and ideas. Is there any knowledge which is independent of culture?

Utilization:
Alkaline hydrolysis of fats is used in the process of soap-making, known as saponification.
• Steroid abuse, especially in sports, and methods for detection.

Syllabus and cross-curricular links:
Topic 10.2—functional groups

Aims:
Aim 7: Use computer animations for the investigation of 3-D visualizations of drugs and receptor sites.

 


D.4 pH regulation of the stomach

Essential idea: Excess stomach acid is a common problem that can be alleviated by compounds that increase the stomach pH by neutralizing or reducing its secretion

Nature of science:
Collecting data through sampling and trialling—one of the symptoms of dyspepsia is the overproduction of stomach acid. Medical treatment of this condition often includes the prescription of antacids to instantly neutralize the acid, or H2-receptor antagonists or proton pump inhibitors which prevent the production of stomach acid. (2.8)

Understandings:
• Non-specific reactions, such as the use of antacids, are those that work to reduce the excess stomach acid.
• Active metabolites are the active forms of a drug after it has been processed by the body.

Applications and skills:
Explanation of how excess acidity in the stomach can be reduced by the use of different bases.
• Construction and balancing of equations for neutralization reactions and the stoichiometric application of these equations.
• Solving buffer problems using the Henderson–Hasselbalch equation.
• Explanation of how compounds such as ranitidine (Zantac) can be used to inhibit stomach acid production.
• Explanation of how compounds like omeprazole (Prilosec) and esomeprazole (Nexium) can be used to suppress acid secretion in the stomach.

Guidance:
• Antacid compounds should include calcium hydroxide, magnesium hydroxide, aluminium hydroxide, sodium carbonate and sodium bicarbonate.
• Structures for ranitidine and esomeprazole can be found in the data booklet in section 37.

International mindedness
Different cultures (ie diet, lifestyle, etc) and genetics can affect the need for pH regulation of the stomach.

Theory of knowledge:
• Sometimes we utilize different approaches to solve the same problem. How do we decide between competing evidence and approaches?

Syllabus and cross-curricular links:
Topic 1.3—calculations involving solutions
Topics 8.2 and 8.4—neutralization
Topic 10.2—functional groups
Topic 20.3—enantiomers
Option B.7—amino acid buffers
Biology option D.1—digestion

 

Aims:
Aim 6: Experiments could include titrations to test the effectiveness of various antacids.


D.5 Antiviral medications

Essential idea: Antiviral medications have recently been developed for some viral infections while others are still being researched

Nature of science:
Scientific collaboration—recent research in the scientific community has improved our understanding of how viruses invade our systems. (4.1)

Understandings:
Viruses lack a cell structure and so are more difficult to target with drugs than bacteria.
• Antiviral drugs may work by altering the cell’s genetic material so that the virus cannot use it to multiply. Alternatively, they may prevent the viruses from multiplying by blocking enzyme activity within the host cell.

Applications and skills:
• Explanation of the different ways in which antiviral medications work.
• Description of how viruses differ from bacteria.
• Explanation of how oseltamivir (Tamiflu) and zanamivir (Relenza) work as a preventative agent against flu viruses.
• Comparison of the structures of oseltamivir and zanamivir.
• Discussion of the difficulties associated with solving the AIDS problem..

Guidance:
• Structures for oseltamivir and zanamivir can be found in the data booklet in section 37.

International-mindedness:
• How has the AIDS epidemic changed since its discovery in the early 1980s?
What is needed to stop the spread of the disease? What is the global impact of this disease?

Syllabus and cross-curricular links:
Options B.2 and B.7—proteins and enzymes
Biology topic 11.1—vaccination

Aims:
Aim 8: The control and treatment of HIV is exacerbated by the high price of anti-retroviral agents and sociocultural issues.

D.6 Environmental impact of some medications

Essential idea: The synthesis, isolation, and administration of medications can have an effect on the environment

Nature of science:
Ethical implications and risks and problems—the scientific community must consider both the side effects of medications on the patient and the side effects of the development, production and use of medications on the environment (ie disposal of nuclear waste, solvents and antibiotic waste). ( 4.8)


Understandings:
High-level waste (HLW) is waste that gives off large amounts of ionizing radiation for a long time.
• Low-level waste (LLW) is waste that gives off small amounts of ionizing radiation for a short time.
• Antibiotic resistance occurs when micro-organisms become resistant to antibacterials.

Applications and skills:
Describe the environmental impact of medical nuclear waste disposal.
• Discussion of environmental issues related to left-over solvents.
• Explanation of the dangers of antibiotic waste, from improper drug disposal and animal waste, and the development of antibiotic resistance.
• Discussion of the basics of green chemistry (sustainable chemistry) processes.
• Explanation of how green chemistry was used to develop the precursor for Tamiflu (oseltamivir).

Guidance:
• The structure of oseltamivir is provided in the data booklet in section 37.

International-mindedness:
• Consider how pharmaceutical companies determine how to spend research funds to develop new medications.
• Do pharmaceutical companies have a responsibility to do research on rare diseases that will not provide them with significant financial profit?
• Production of a drug typically involves a number of different organic reactions.
What are the ethics governing the design (synthesis) of drugs?
Do standards and practices vary by country and region?

Theory of knowledge
How do we balance ethical concerns that appear to be at odds with each other
when trying to formulate a solution to the problem?

 

Aims:
Aim 8: How do we safely dispose of medicinal nuclear waste?
• Aim 8: The Pacific yew tree which is the source of the chemotherapy drug Taxol is facing extinction.
• Aim 8: Solvent disposal is a growing environmental problem.

D.7 Taxol—a chiral auxiliary case study

Essential idea: Chiral auxiliaries allow the production of individual enantiomers of chiral molecules.

Nature of science:
Advances in technology—many of these natural substances can now be produced in laboratories in high enough quantities to satisfy the demand. (3.7)
Risks and problems—the demand for certain drugs has exceeded the supply of natural substances needed to synthesize these drugs. (4.8)

Understandings:
Taxol is a drug that is commonly used to treat several different forms of cancer.
• Taxol naturally occurs in yew trees but is now commonly synthetically produced.
• A chiral auxiliary is an optically active substance that is temporarily incorporated into an organic synthesis so that it can be carried out
asymmetrically with the selective formation of a single enantiomer.

Applications and skills:
Explanation of how taxol (paclitaxel) is obtained and used as a chemotherapeutic agent.
• Description of the use of chiral auxiliaries to form the desired enantiomer.
• Explanation of the use of a polarimeter to identify enantiomers.

Guidance:
• The structure of taxol is provided in the data booklet in section 37.

International-mindedness:
• There is an unequal availability and distribution of certain drugs and medicines
around the globe.

Syllabus and cross-curricular links:
Topic 20.2—synthetic routes
Topic 20.3—stereoisomerism

Aims:
Aim 8: Consider the ethical implications of using synthetic drugs instead of natural sources.

D.8 Nuclear medicine

Essential idea: Nuclear radiation, whilst dangerous owing to its ability to damage cells and cause mutations, can also be used to both diagnose and cure diseases.

Nature of science:
Risks and benefits—it is important to try and balance the risk of exposure to radiation with the benefit of the technique being considered. (4.8)

Understandings:
• Alpha, beta, gamma, proton, neutron and positron emissions are all used for medical treatment.
• Magnetic resonance imaging (MRI) is an application of NMR technology.
• Radiotherapy can be internal and/or external.
• Targeted Alpha Therapy (TAT) and Boron Neutron Capture Therapy (BNCT) are two methods which are used in cancer treatment.

Applications and skills:
• Discussion of common side effects from radiotherapy.
• Explanation of why technetium-99m is the most common radioisotope used in nuclear medicine based on its half-life, emission type and chemistry.
• Explanation of why lutetium-177 and yttrium-90 are common isotopes used for radiotherapy based on the type of radiation emitted.
• Balancing nuclear equations involving alpha and beta particles.
• Calculation of the percentage and amount of radioactive material decayed and remaining after a certain period of time using the nuclear half-life equation.
• Explanation of TAT and how it might be used to treat diseases that have spread throughout the body.

Guidance:
Common side effects discussed should include hair loss, nausea, fatigue and sterility.
Discussion should include the damage to DNA and growing or regenerating tissue.
• Isotopes used in nuclear medicine including; Tc-99m, Lu-177, Y-90, I-131 and Pb-212.

International-mindedness:
• The use of nuclear technology in medical treatments is not consistent across the globe. Culture, cost, availability and beliefs are some factors that can influence its use.

Theory of knowledge:
• There is often no reference to the term “nuclear” in MRI. Are names simply labels or do they influence our other ways of knowing? How does public
perception influence scientific progress and implementation?

Syllabus and cross-curricular links:
Topics 11.3 and 21.1—NMR
Options C.3 and C.7—nuclear reactions and half-life
Physics option C.4—medical imaging.

 

D.9 Drug detection and analysis

Essential idea: A variety of analytical techniques is used for detection, identification, isolation and analysis of medicines and drugs

Nature of science:
Advances in instrumentation—advances in technology (IR, MS and NMR) have assisted in drug detection, isolation and purification. (3.7)

Understandings:
• Organic structures can be analysed and identified through the use of infrared spectroscopy, mass spectroscopy and proton NMR.
• The presence of alcohol in a sample of breath can be detected through the use of either a redox reaction or a fuel cell type of breathalyser.

Applications and skills:
Interpretation of a variety of analytical spectra to determine an organic structure, including infrared spectroscopy, mass spectroscopy and proton NMR.
• Description of the process of extraction and purification of an organic product.
• Consider the use of fractional distillation, Raoult’s law, the properties on which extractions are based and explaining the relationship between organic structure and solubility.
• Description of the process of steroid detection in sport utilizing chromatography and mass spectroscopy.
• Explanation of how alcohol can be detected with the use of a breathalyser.

Guidance:
Students should be able to identify common organic functional groups in a given compound by recognition of common drug structures and from IR
(section 26 of the data booklet), 1HNMR (section 27 of the data booklet) and mass spectral fragment (section 28 of the data booklet) data.
• A common steroid structure is provided in section 34 in the data booklet.

International-mindedness:
The misuse of drugs in sport is an international problem.

Theory of knowledge:
Developments in technology have increased the chances of people being caught using illegal substances. How do changes in technology influence our ethical choices?

 

Syllabus and cross-curricular links:
Topic 10.2—functional groups

Aims:
• Aim 4: A variety of spectroscopy techniques can be used to identify newly
developed molecules.
• Aim 7: Computer databases with spectroscopy data could be used to confirm
the identity of newly synthesized molecules.
• Aim 8: Developments in technology have increased the chances of people
being caught using illegal substances. How do changes in technology influence
our ethical choices?

 

B.10 Stereochemistry in biomolecules

Essential idea: Most biochemical processes are stereospecific and involve only molecules with certain configuration of chiral carbon atoms

Nature of science:
Theories used to explain natural phenomena/evaluate claims—biochemistry involves many chiral molecules with biological activity specific to one enantiomer. Chemical reactions in a chiral environment act as a guiding distinction between living and non-living matter. (2.2)

Understandings:
With one exception, amino acids are chiral, and only the L-configuration is found in proteins.
• Naturally occurring unsaturated fat is mostly in the cis form, but food processing can convert it into the trans form.
• D and L stereoisomers of sugars refer to the configuration of the chiral carbon atom furthest from the aldehyde or ketone group, and D forms occur most frequently in nature.
• Ring forms of sugars have isomers, known as α and β, depending on whether the position of the hydroxyl group at carbon 1 (glucose) or carbon 2 (fructose) lies below the plane of the ring (α) or above the plane of the ring (β).
• Vision chemistry involves the light activated interconversion of cis- and transisomers of retinal.

Applications and skills:
• Description of the hydrogenation and partial hydrogenation of unsaturated fats, including the production of trans-fats, and a discussion of the advantages and disadvantages of these processes.
• Explanation of the structure and properties of cellulose, and comparison with starch.
• Discussion of the importance of cellulose as a structural material and in the diet.
• Outline of the role of vitamin A in vision, including the roles of opsin, rhodopsin and cis- and trans-retinal.

Guidance:
Names of the enzymes involved in the visual cycle are not required.
• Relative melting points of saturated and cis-/trans-unsaturated fats should be covered.

International-mindedness:
• Different countries have very different standards of food labelling with respect to its chemical content, including the type of fats present.

Syllabus and cross-curricular links:
Topic 10.1—organic functional groups
Topic 20.1—organic reactions
Topic 20.3—stereoisomerism
Option A.4—intermolecular/London forces

Aims:
Aim 8: Ethical questions arise through the use of saturated and trans-fats, particularly in the fast-food industry.