C2 Physicochemical properties

Question 1

meaning of MW abbreviation

Answer 1

molecular weight

Question 2

meaning of HBA abbreviation

Answer 2

hydrogen bond acceptor

Question 3

meaning of HBD abbreviation

Answer 3

hydrogen bond donor

Question 4

compare logP and logD simply

Answer 4

• logP is a measure of lipophilicity
• logD is a measure of lipophilicity and takes ionisation into account

Question 5

what is a HBD? give 2 examples

Answer 5

• donates a hydrogen bond
• eg. N-H, O-H

Question 6

what is a HBA? give 2 examples

Answer 6

• accepts a hydrogen bond through its lone pair
• eg. N, O

Question 7

what is the HBD of a molecule?

Answer 7

total number of NH and OH bonds

Question 8

what is the HBA of a molecule?

Answer 8

total number of N and O atoms with available lone pairs

Question 9

in the picture, which molecule is the HBA and which is the HBD?

Answer 9

• left is the HBD as it is the molecule offering the hydrogen
• right is the HBA but it also has OH groups that can be hydrogen bond donors

Question 10

pictured here, how many HBA does cholesterol have?

Answer 10

1

Question 11

pictured here, how many HBD does cholesterol have?

Answer 11

1

Question 12

pictured here, how many HBA does progesterone have?

Answer 12

2

Question 13

pictured here, how many HBD does progesterone have?

Answer 13

0

Question 14

describe resonance and hybridisation of nitrogen in amides

Answer 14

• amides exhibit a resonance effect
• in these cases, nitrogen is sp2 hybridised
• nitrogen lone pair occupies an unhybridised p-orbital
• there is a pi-system above and below the plane of the O=C-N bond

Question 15

definition of conjugated

Answer 15

system of overlapping p orbitals containing delocalised electrons

Question 16

definition of resonance

Answer 16

a way of describing bonding based on the ‘average’ structure as a result of different contributing forms

Question 17

in terms of HBA and HBD, what does an OH group contain?

Answer 17

1 HBD
1 HBA

Question 18

in terms of HBA and HBD, what does an amide group contain?

Answer 18

1 HBD (N-H)
1 HBA (O)

Question 19

why is there not 2 HBA in an amide group?

Answer 19

the lone pair on N is delocalised and unavailable

Question 20

what is the partition coefficient (P)?

Answer 20

• a measure of lipophilicity
• imagine how a solid would distribute in a separating funnel containing equal amounts of aqueous and organic solvents
• (how does it distribute between the layers?)

Question 21

what is the word formula for P (partition coefficient)?

Answer 21

[Molecule]octanol / [Molecule]water

Question 22

describe what logP is and its typical range

Answer 22

• logP is the main descriptor of lipophilicity
• typical range is roughly -5 to +7

Question 23

if logP = 5, what does this mean? describe other general values of logP

Answer 23

• if logP = 5, the molecule is 10^5 times more soluble in the organic solvent than the aqueous
• the higher the logP, the more lipophilic the molecule
• logP can be negative for polar molecules (because the solute is far more soluble in water than octanol)

Question 24

GENERALLY, are carbon-based groups lipophilic or hydrophilic?

Answer 24

lipophilic

Question 25

GENERALLY, are nitrogen and oxygen groups lipophilic or hydrophilic?

Answer 25

- polar / hydrophilic - they are electronegative and create dipoles

Question 26

GENERALLY, are aryl halogens lipophilic or hydrophilic?

Answer 26

- lipophilic - larger halogens are more lipophilic (fluorine is small and so is the least lipophilic compared to chlorine and bromine etc)

Question 27

GENERALLY, are charged groups lipophilic or hydrophilic?

Answer 27

very polar

Question 28

describe the solubility of tails of phospholipids and why they are like this

Answer 28

- very lipophilic - this is because they lack heteroatoms

Question 29

describe the solubility of heads of phospholipids and why they are like this

Answer 29

- hydrophilic / polar - has lots of heteroatoms and lots of HBAs and HBDs

Question 30

explain how particle size affects passive diffusion through membranes

Answer 30

- to be absorbed, a drug must somehow cross membranes - passive diffusion is the most common form of membrane transport - depends on drug size and lipophilicity - smaller drugs diffuse faster than larger drugs

Question 31

explain how lipophilicity affects passive diffusion through membranes

Answer 31

- too polar = cannot passively diffuse across the lipophilic cell membrane (gets stuck in the extracellular fluid in the water) - too lipophilic = more susceptible to metabolism (may not be water-soluble to move into and through the membrane or may get stuck in the middle of the bilayer)

Question 32

what is Lipinski's rule of 5?

Answer 32

- 4 rules used as a guide to design molecules which are likely to be orally absorbed logP≤5 MW≤500 HBA≤10 HBD≤5

Question 33

state 3 molecules that are exceptions to Lipinski's rule of 5

Answer 33