Option D.2: Aspirin and Penicillin- Structures in section 37 of data booklet

Pain Detection and Response

Mild Analgesics• Salicylic acid and its derivatives (aspirin and

paracetamol)– block the transmission of pain from source

– interfere with/ suppress the production of substances (prostaglandins) by the injured tissues.

• Prostaglandins stimulate pain receptors that send pain impulses to the brain and that cause swelling and fever.

• Do not interfere with brain function (like strong analgesics/narcotics)

Salicylic Acid• Analgesic for old timey people- Hippocrates and Pliny

the Elder (go listen to Sawbones) • Unpleasant to take– Bitter taste– Acidity = irritating to the stomach/ damaged the

membranes in the mouth, gullet and stomach

• What functional groups does salicylic acid have?

Aspirin• Derivative of salicylic acid. • How are the functional groups

different?

– Salicylic acid was converted into aspirin by esterification

Synthesis of aspirin: Method

• The product is cooled to form crystals which are then suction filtered and washed with cold water (aspirin not soluble in cold water) - What is removed?

• Concentrated H2SO

4 is

added to the reaction (catalyst) mixture which is warmed gently.

Synthesis of aspirin: Purification• Recrystallization: - animation– dissolve the impure crystals in a small volume

of hot ethanol (better solubility of aspirin)– Water is added to the solution and the

solution is cooled slowly and chilled• Why slowly? • Aspirin recrystallizes out. What will be left

in the solution?

o The pure crystals are removed using filtration.

Testing Aspirin Purity

• Find the melting point! – Pure substances have a well

defined melting point (small range) • Pure Aspirin: 138-140 0C

• Salicylic Acid: 159 0C

• Mixture: lower and less defined mp

Characterization of aspirin: IR

• Characterization = determining identity of a product.

•Using IB data booklet, compare and contrast the IR spectrum for salicylic acid and aspirin.

Characterization of aspirin: IR

• Common:o A strong C-O peak from 1050 to 1410 cm-1 in alcohols and

esterso A strong peak at 1700 -1750 cm-1 for C=O in carboxylic acid

group.o A strong, broad O-H peak at 3200 - 3600 cm-1 in salicylic

acid.

• Different:o The ester group in aspirin at 1700 to 1750 cm-1 which is not

there in salicylic acid as salicylic acid does not have an ester group.

o The absence of hydroxyl group in aspirin means that there is no peak at 3200 to 3600 cm-1.

Beneficial side effects of aspirin In addition to acting as an analgesic, aspirin also:

o Acts as an anticoagulant as it reduces blood clotting

o Prevents the recurrence of heart attacks and strokes as it thins the blood.

o Aspirin also seems to prevent colon cancer. Medicines taken for preventative measures are also referred to as a prophylactic.

Negative side effects of aspirin ○ Anticoagulant (negative for people with

blood clotting disorders)

○ irritation and ulceration of stomach

■ can lead to bleeding

○ How to reduce these?

■ Coatings to delay activity until it has reached the small intestine

○ Many people are allergic (esp. asthmatics)

○ Reye’s Syndrome in <12 year olds

■ potentially fatal liver/brain disorder

Synergetic effect of aspirin with ethanol

• Ethanol produces a synergic effect with a number of drugs including aspirin– Synergetic = effect of the drug is

enhanced – Can be dangerous e.g. aspirin and

ethanol together can increase risk of stomach bleeding.

Increasing bioavailability of aspirin

• Very low solubility in water (largely nonpolar)– Has a carboxylic acid group, can be made into an

ionic salt by reacting it with a strong base to form a soluble sodium salt• Forming ionic salt = increased solubility in

water (ie. Soluble Aspirin)– Why does increasing solubility in water

increase the bioavailability?

Penicillins

• Antibacterials: drugs that kill or inhibit the growth of bacteria that cause infectious diseases.

• Penicillins are a group of compounds that are produced by fungi and kill harmful microrganisms

– antibiotics or antibacterials.

Penicillin and the Beta-lactam group• Penicillin G shown in the IB Data booklet.

• The main part of the structure is the beta-lactam

ring. • 4-membered ring with a cyclic amide• Responsible for its antibacterial properties• small bond angles (90°) = strain on bonds =

weak bonds that easily react

How do penicillins work? • Prevent the growth of bacteria• Beta-lactam ring disrupts the formation of cell walls– Deactivates the enzyme transpeptidase – High reactivity of beta-lactam group causes it to

bind irreversibly near the active site of the enzyme

How do penicillins work? • Inactivation of Enzyme

(transpeptidase)– blocks process of cell

wall construction• prevents polypeptide

cross links from forming between mucopeptide chains

• No strengthened links = weak cell wall– Cell bursts and

dies

Disadvantages of Penicillin G

● Broken down by stomach acid○ must be injected directly

into bloodstream● Can make different forms

of penicillin by modifying the side chain (R group) ○ retains activity (no change

to beta-lactam)● Many people have allergies

to penicillin

Antibacterial Resistance: Penicillin

● As a result of genetic mutations, bacteria have become resistant to penicillins.○ Causes the break-up of the

beta-lactam ring (no activity) ○ These bacteria then reproduce and

pass on their resistance to succeeding generations.

The more opportunities there are for the mutation into antibiotic resistant bacteria.

Modification of Side Chain

● Modified side chains can prevent binding of the enzyme that breaks the beta-lactam group○ Reduce antibiotic resistance○ Increase resistance to stomach acid○ Reduce allergic reactions

Examples of modified penicillins that are able to resists penicillinase

oxacillin methicillin

Responses to Antibacterial Resistance

● Modified side chains● Antibiotics = prescription only○ not used incorrectly for non-bacterial

issues● Patient Compliance

Spread of Drug Resistant Bacteria

Spread of Drug Resistant Bacteria

● Patient compliance○ Patients not completing the full

course of penicillins = prolonging the disease as not all bacteria are killed■ Bacteria to live longer = more mutations

= more bacteria with resistance. ■ Patient compliance also allows disease

to spread as bacteria are not all killed.