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

What are ethers and their properties (7)

Answer 2

1. Ethers area class of organic compounds that contain oxygen between two alkyl groups. They have the formula R-O-R’, with R’s being the alkyl groups.
2. R and R1 can be different or identical.
3. R and R1 can be aliphatic or aromatic.
4. Ethers are acceptors of hydrogen bonds because of the high density of electrons around the oxygen
5. Ethers group can be used to improve the water solubility of a drug (compared to alkyl)
6. Ethers are metabolically inert, so they can be used to avoid first-pass metabolism.
7. Phenyl ethers can be used as prodrug phenols

Question 3

What are thiols and thioethers and their properties (7)

Answer 3

1. Thiols is the sulphur equivalent to an alcohol
2. Thioethers are the sulpher equivalent to ethers where sulfur is between two alkyl groups
3. R and R1 can be different or identical
4. R and R1 can be aliphatic or aromatic
5. S is less electronegative than O
6. C-S and S-H bonds are not polar
7. Both functions are electron-rich (electron donating) so they can behave as nucleophiles

Question 4

What are halides (or haloalkanes) and their properties (4)

Answer 4

1. Carbon bonded to F, Cl, Br or I
2. There are four types: primary, secondary, tertiary and aromatic
3. primary haloalkanes can behave as electrophiles (accept electrons)
4. metabolism of terminal halides leads to toxic species

Question 5

What are aldehydes and ketones and their properties (6)

Answer 5

1. In aldehydes C=O is at the end of the molecule
2. ketones, C=O is within the molecule
3. R and R1= identical/different, aliphatic/aromatic
4. Aldehydes are more electrophilic than ketones and quickly react with neutrophils in vivo
5. Ketones are more stable but often the ‘’weak point’’ in the molecule
6. The C atom in carbonyl is an electrophile (EWG)

Question 6

What are nitro groups and their properties (6)

Answer 6

1. Nitro groups contain O=N-O
2. R aliphatic or aromatic
3. Nitro group has separate charges
4. The separate negative charges make the nitro group HIGHLY polar
5. Due to resonance, the nitrogen is electron-poor and the group acts as a strong EWG (withdrawing an electron from the nitrogen breaking the double bond and gives the Nitrogen 2+ charge)
6. The metabolism of nitro group (reductive) leads to the formation of toxic species

Question 7

What are esters and their properties (3)

Answer 7

1. Esters are characterised by O=C-O
2. 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 8

What are amides and their properties (3)

Answer 8

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 9

What are carbamates and their properties (5)

Answer 9

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 10

What are ureas and their properties (6)

Answer 10

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. The 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