Polarity, hydrogen bonding and drug behaviour

Question 1

What are the types of alcohols and their properties (7)

Answer 1

1. primary
2. secondary
3. tertiary
4. aromatic (phenol)
5. The metabolism of alcohol is mainly oxidative - primary → aldehyde, secondary → ketone.
6. O is an H-bond acceptor and H is an H-bond donor
7. C-O bond in alcohols is polar

Question 2

How are alcohols metabolised (3)

Answer 2

1. Primary oxidative
2. Primary → aldehyde
3. Secondary → ketone

Question 3

What are the properties of alcohols (3)

Answer 3

1. O is a H-bond acceptor
2. H is a H-bond donor
3. C-O bond is polar

Question 4

What are ethers (5)

Answer 4

1. Oxygen between two alkyl groups (R-O-R’)
2. Accept H-bonds
3. Improve water solubility
4. Metabolically inert - avoid first pass
5. Phenyl ethers = pro-drug phenols

Question 5

What are the properties of ethers (2)

Answer 5

1. R and R1 can be different or identical.
2. R and R1 can be aliphatic or aromatic.

Question 6

What are thiols (2)

Answer 6

1. Sulphur equivalent to alcohol (SH/ R-S-R1)
2. electron donating

Question 7

What are the properties of thiols (4)

Answer 7

1. R and R1 can be different or identical
2. R and R1 can be aliphatic or aromatic
3. S is less electronegative than O
4. C-S and S-H bonds are not polar

Question 8

What are halides (4)

Answer 8

1. Carbon bonded to F, Cl, Br or I
2. primary, secondary, tertiary and aromatic
3. primary haloalkanes = electrophiles (accept electrons)
4. metabolism of terminal halides = toxic species

Question 9

What are aldehydes and ketones (3)

Answer 9

1. aldehydes C=O is at the end of the molecule
2. ketones C=O is within the molecule
3. R and R1 can be identical or different, aliphatic or aromatic

Question 10

What are the properties of aldehydes and ketones (3)

Answer 10

1. Aldehydes are more electrophilic than ketones
2. Ketones are more stable but often the ‘’weak point’’ in the molecule
3. The C atom in carbonyl is an electrophile (accepts electrons breaking the double bond)

Question 11

What are nitro groups and their properties (6)

Answer 11

1. contain O=N-O
2. R aliphatic or aromatic
3. Nitro group has separate charges
4. The separate charged = HIGHLY polar
5. Resonance = EWG
6. Reductive metabolism = toxic species

Question 12

What are esters and their properties (3)

Answer 12

1. Esters are characterised by O=C-O
2. The ester group is polar and is an acceptor (but not a donor) of H bonds
3. Esters can undergo enzyme-catalysed hydrolysis: this can be exploited to make a prodrug

Question 13

What are amides and their properties (3)

Answer 13

1. Amides are characterised by O=C-NH2
2. R groups can be identical or different, aliphatic, aromatic or H
3. As esters, amides can be used as prodrugs, although they are more stable to hydrolysis

Question 14

What are carbamates and their properties (5)

Answer 14

1. A carbamate isa category of organic compoundswith the general formula R 2 NC(O)OR and structure >N−C(=O)−O−
2. Groups can be identical or different
3. R2 and R1 can be aliphatic, aromatic or H
4. =O and N and O act as H bond acceptors
5. C in carbamate is less electron-poor than an ester C due to the delocalisation of the N lone pair (resonance). This makes it more resistant to hydrolysis.

Question 15

What are ureas and their properties (6)

Answer 15

1. Urea is a diamide of carbonic acid, isan organic compound with chemical formula CO(NH2)2.
2. This amide has two amino groups (–NH2) joined by a carbonyl functional group (–C(=O)–).
3. Urea is a highly hydrophilic group
4. Stability of ureas is similar to that of amides (more stable to hydrolysis)
5. R can be identical or different, aliphatic or aromatic
6. N, =O and H act as H bond acceptors