IB Chemistry Option D: Medicinal Chemistry (SL)

Direct research and development based on traditional leads for medicines or drugs

Identification of need, determination of structure, synthesization, extraction, measurement of percent yield, testing

1. Discovery - natural source is identified and compounds are extracted
2. Pre-clinical animal trials test about 250 compounds
3. Passing compounds are used in clinical trials w increasing number of volunteers
4. The final compound is selected, approved, and manufactured to produce a new drug.

Inhalation, ingestion, rectal suppositories, injections (into blood, muscle, or under skin), absorption

Oral administration is easy and preferable to patients

Drugs that are administered orally may take longer to be absorbed into the body and absorption can be unpredictable due to degradation by stomach acids and enzymes

Target specific cells called target sites, and bind with them to inhibit or promote certain effects.

The body's adaptation to a drug, which causes a need for a higher dosage in order to achieve the original effect

The amount of the administered dosage which reaches the target site - varies based on structure, means of administration, dosage of the drug.

- They need to be absorbed into the body and cells
- Polar groups allow blood absorption (Ex. hydroxl, carboxyl, amino groups)
- Nonpolar to pass through cell membranes (Ex. esters, ether, phenyl rings)

window - The range between the toxic dose and minimum effective dose of a drug

TI = TD50/LD50

Low TI = little difference between effective and toxic dose = MORE DANGEROUS

High TI = large difference between ED and TD = LESS DANGEROUS

The lethal dose; a sample dosage of a drug that kills 50% of tested lab rats

The toxic dose; a sample dosage of a drug that is toxic to 50% of humans

The effective dose; a sample dosage of a drug that has the desired effect on 50% of test subjects

Alteration of mood/emotion OR alteration of sensory perception

The range of doses between the minimum effective dosage and the dosage that brings about undesirable effects; a wide range is desirable

Derivatives of opium, called opiodes, that relieve pain by intercepting stimulus at the source, by stopping prostaglandin production
Ex. Aspirin

Local ingestion via oral consumption

salicylic acid + acetic anhydride --> Acetylsalicylic acid + acetic acid

Reagents: H2SO4
conditions: heat

Recrystallisation

Used to removed remaining impurities to make a more effective drug

1. Add solvent (i.e. ethanol) and heat to dissolve
2. Set in ice bath to lower temperature to allow crystallisation
3. Collect solid product through filtration of impurities

Testing melting point range
- Pure aspirin has MP of 136
- More impure = lower or more different MP

Infrared Spectroscopy (IR)
- Identify number of bonds present

The prevention of prostaglandin synthesis produces an analgesic effect because prostaglandins are the molecules that cause pain, swelling, and inflammation.

intended to prevent disease

Aspirin is also prophylactic, working as an anticoagulant to prevent strokes and heart attack

Stomach ulcers, tinnitus, bleeding of the stomach lining, risk of hemorrages

Paracetamol has less pronounced side effects than aspirin

Paracetamol has a more narrow therapeutic window

Esterification

salicylic acid + ethanoic anhydride ---> acetylsalicylic acid (aspirin) + ethanoic acid

- Can be reacted to form SODIUM ACETYLSALICYLATE which is more soluble
- Consumption with alcohol has a synergistic effect

The carboxyl group

Sodium hydroxide

This drug is used to treat bacterial infections

Diarrhea, nausia, fever, rashes

Penicillin will bind to the enzyme that bacteria use to synthesize their cell walls, blocking the active site. The cell wall then breaks, allowing water to enter the cell and causing the cell to burst.

It's bond angles make it highly strained, allowing it to break/open up.

Bacteria has evolved to become resistant to antibiotics because resistant mutants survive through treatment and are able to reproduce, creating offspring that are also resistant to specific antibiotic treatments.

Penicillinase is able to break the beta-lactam ring and inhibit the function of the molecule

Opiates which bind with opioid receptors in the brain to inhibit the central nervous system

All 3 compounds have a phenyl group and a tertiary amino group (amine).

Morphine - two hydroxyl groups
Codeine - one hydroxyl replaced w alkyl group
Diamorphine - esterification replaces both -OH groups with esters

Codeine < Morphine < Diamorphine

Why?
Codeine is the least soluble, but has more bioavailability
Morphine is more polar but less bioavailability
Diamorphine has the greatest effect

Esterification

Strong analgesics (opiates) are fast-acting and more effective.

Addiction is potential when using strong analgesics (opiates), and the development of social problems (theft, prostitution) may occur, as well as the development of health problems (AIDS, constipation).

Heroin is less polar, making it soluble in lipids. This allows it to cross the blood-brain barrier, metabolize into morphine, and bind directly to opiod receptors.

Acetoxy group (OC(=O)CH3)

Ethanoic anhydride

The bioavailability will increase because the compound becomes more soluble.

Codeine

Diamorphine

An opiate derivative which can be used to treat addiction without the euphoric effects

Drugs taken orally to relieve symptoms of strong stomach acid (i.e. heart burn, indigestion, acid reflux)

An agent added to create a neutralising layer to stop reflux

An agent which stops the foaming of mucus caused by increased gas production.
Ex. dimethicone

Kidney stones, blood pH too low, renal failure, increased bloating/flatulence, hypertension

Al(OH)3 + 3 HCl ---> 3H2O + AlCl3

MgCO3 + 2HCl ---> MgCl2 + H2CO3

Aluminum hydroxide

Stomach is able to regulate is pH using a buffer of carbonic acid and hydrogen carbonate

Henderson-Hasselbalch equation

pH = pKa + log ([A-]/[HA]

A- = conjugate base
HA = weak acid

1) inhibiting acid synthesis
2) inhibiting acid secretion
--> Caused be interfering with key receptors in the process

Histamine
Gastrin
Acetylcholine

-Binds with histamine receptor to stop production of acid.

Ranitidine/Zantog
- ionic charges make it soluble
- 40-80% bioavailability
- Must be turned into active metabolite

- Restrict acid release by binding with H+ pumps in the cell membranes
- More effective than H2 receptor antagonist

- Omeprazole
- higher bioavailability - lasts 1-3 days
- Must be turned into active metabolite

- Viruses have a protein coating while bacteria have cell walls/membranes.
- Virus need host to metabolise, bacteria metabolise themselves
- Virus much smaller / Bacteria bigger

1. Virus attaches to host cell
2. Viral DNA injected into cell
3. Viral DNA replicated using metabolic processes of host
4. New protein coats for viruses are made
5. Mature virions assembled in cell
6. Cell ruptures and releases mature viruses

- Helper T-Cells must recognise viral/abnormal cells before new viruses are released
- A secondary viral infection is fought by memory B-cells releasing antibodies to mark viruses

- Fight virus before infection
A weakened form is injected and causes an immune response without the infection = body ready to fight if actual virus enters

- Fight virus after infection
- Target different steps in the viral process
- Ex. block entrance, interfering w/ replication or release from cells

- The flu
- Causes: headache, fever, runny nose, sore throat, etc.

Oseltamivir /Tamiflu and Zanamivir/Relenza

Block rupturing of cell to release new virus by binding to neuraminidase

Oseltamivir: ester, carbonyl group
Zanamivir: alcohol, carboxyl
Bother: ether

A retro virus that attacks the bodies T-cell that compromises the body's immune system, leading to AIDS

Contains viral RNA not DNA - therefor is more subject to mutation

- A mixture of drugs which target various stages in the viruses cycle
- Decrease the rate of transmission of the virus, but do not stop HIV

Small mutations in viral reproduction make new strains

Two strains of virus resulting in a new variation

The leftovers created by the product and use of medicine which can have negative effects on the environment

Drug synthesis often uses solvents; these are majority of waste
Ex. water, alcohols, alkanes, benzenes

- Benzene = carcinogenic
- Hexane = numbness in limbs and stunted plant growth
- Ethers = dizziness in mammals vs. dehydration in plants

Incorrect disposal or incomplete use of perscription

- Increased antiobiotic resistance
- Harmful to bacteria in ecosystems
- Influence in food systems (water/food sources) spreads resistance in humans
= Reduced efficiency

Waste produced by use of radioactive substances (i.e. radioisotopes)

High-level waste account for 4% of waster
- Very radioactive
- Stored in wet storage so it can decay and be shielded
Low-level waste accounts for 90%
- Protective clothing, tools, etc.
- Can be disposed in dry storage

- Radiation exposure can have bad impacts
- Radiation sickness
- DNA mutation leading to disabilities
- Cancer, infertility, death

A branch of science attempting to reduce waste and energy consumption related to production

- Fraction distillation allows for recycling of solvents
- Biodegradation breaks down solvents (i.e benzene) using bacteria and organic compounds

Biosynthesis demands less from natural sources and produces less waste and energy.

Theoretical yield (g) = moles of reactant (mols) x mass of product (g)

Percent yield (%) = actual yield / theoretical yield