Week 1

Question 1

What does polarisation mean?

Answer 1

Large differences in electronegativity (EN>0.5) causes unsymmetrical distribution of electrons within a bond.

Question 2

Describe the pattern of electronegativity in the periodic table.

Answer 2

Fluorine is the most electronegative element and electronegativity decreases as you move down the periodic table and to the left.

Question 3

What is hydrogen bonding?

Answer 3

Any bonds electronegative bonds made between H and NOF (Nitrogen, Oxygen and Fluorine).

Question 4

What does water solubility mean? And how does it occur?

Answer 4

Water solubility id the ability of substances to dissolve in water. In order for substances to dissolve in water, they must interact with water molecules through H-bonding or charge-charge interaction.

Question 5

What does the terms “hydrophilic” and “hydrophobic” mean?

Answer 5

Hydrophilic = 'Water loving'
Hydrophobic = 'Water hating'

Question 6

Why does petrol not dissolve in water? Describe the mechanism behind this?

Answer 6

Petrol does not dissolve in water as the molecule cannot be surrounded by water bc petrol oil is not polarised and as it is lighter it will float on top.
The more polar molecules in a molecule -> more solubility

Question 7

What are the pH's of the following areas inside the body?
Stomach (EMPTY)
Stomach (FULL)
Intestine
Blood

Answer 7

pH Stomach (EMPTY) = 1-1.5
pH Stomach (FULL) = 2-4
pH Intestine = ~8
pH Blood = 7.4

Question 8

What are the stages of drug action?

Answer 8

1. Absorption and Distribution of the drug sight (‘getting there’)
2. Binding of the drug to the target site (‘acting at the target’)
3. Metabolism and Excretion (‘getting out’)

Question 9

What is crucial for absorption and distribution of a drug?

What is crucial for the binding of a drug?

Answer 9

Distribution and Absorption = hydrophobicity - (passage throguh nonpolar cell membranes; lipid bilayers); hydrophilicity - (transport of drug in blood)
Binding = Shape - (fitting into target site); polarization or atoms/bonds (‘attracting’ bonding interaction)

Question 10

How do drugs bind?

Answer 10

“LOCK AND KEY HYPOTHESIS” Common drug targets (‘locks’) are enzymes (or nucleic acids). Drug (‘key’) interacts with these targets at binding site (hollow or canyon on the surface) through ‘attracting’ functional (binding) groups.

Question 11

What are enzyme inhibitors?

Answer 11

Enzyme inhibitors hinder or prevent enzymes acting as catalysts for a particular reaction. Enzyme inhibitors should be: similar to natural substrate or product, should fit into active site.

Question 12

What are the different types of enzyme inhibitors and their mechanisms?

Answer 12

Competitive Binding = drug is competing with natural substrate for the active site (if a drug takes this active site on the enzyme, it is no longer available to undergo normal function
Reversible Inhibition = binding of drug through non-covalent intermolecular bonds.
Irreversible Inhibition = permanent blocking of enzyme by forming a covalent (‘real’) bond, e.g. via amino acids with nucleophilic groups. Permanent chemical change.

Question 13

What are HBD and HBA and examples?

Answer 13

HBD = Hydrogen bond donor group X-H (X=N, O, S)
HBA = Hydrogen bond acceptor group Y (Y= O, N, F, Cl)
Some groups can act as HBA and HBD e.g. -OH, -NH2

Question 14

What are the different types of inter molecular bonding forces?

Answer 14

Van der Waals/London disperion interactions
Dispersion Forces
Dipole Dipole Forces
Hydrogen Bonding

Question 15

Describe real life applications/examples of Irreversible Inhibition.

Answer 15

Drugs with irreversible covalent binding = usually very toxic (side effects), difficult to control ‘safely’, long-acting (irreversible).
Applications: chemotherapeutic agents - intended to kill disease-causing invaders. Selectively toxic (for most antibacterial, anti fungal and other anti parasitic drugs) = irreversible binding to vital cellular component of intruder
Cancer chemotherapy = low selectivity
Penicilin = highly toxic to bacteria through irreversible inhibition of enzyme that is crucial to bacteria’s cell wall synthesis

Question 16

What is Lipinski’s rule of 5 and what does it determine?

Answer 16

Lipinski’s rule of 5 determines the drug likeliness for that drug to be orally active (orally bioavailable). Drug likeliness depends on water solubility and binding. Lipinski;s rule is based on key-features that relate to these properties and are commonly found in orally active drugs.
4 Criteria
1. H-bond donors (OH, NH <=5)
2. H-bond acceptors (O, N <=10)
3. Molecular weight <= 500g/mol
4. Partition coefficient Log P <= 5
Caution: neither quantitative nor foolproof

Question 17

How do acid-base properties effect drugs?

Answer 17

Most drug molecules are weak acds or weak bases. Their acid-base (A-B) properties are important because:

• A-B properties affect ionisation of the drug in ‘vivo’ with consequent effects on absorption (disfavouring) and distribution (favouring)
• Production of salts of acids or bases may increase drug solubility and shelf-life
• Drugs are exposed to various pHs within the body

Question 18

What does the pKa value refer to?

Answer 18

The strengths of an acid or base is expressed by the pKa value, which is a characteristic property of the molecule or functional group.
Acids:
- Acids (HA) react with water to their anion (A-) and H3O+ (H+)
- The smaller the pKa the STRONGER the acid
- Most commone in drugs: carboxyl groups (-COOH) with pKa of 5 to 6
Bases:
- Bases (B:) react with water to their cations (BH+) and HO-
- The larger the pKa the stronger the base
- Most common in drugs: amino groups

The pKa is important in comparision to teh pH of the ‘environment’ e.g. inside the stomach (pH 1-4), intestine (pH ~8) or blood (pH 7.4)

Question 19

Hey you!

Answer 19

Look over the GLS questions