Ionising Groups in Drugs - Bases

Question 1

pka rules of bases?

Answer 1

Base strength is given in terms of the pKa (acidity) of the protonated base

Strong base = high pKa of protonated base

Weak base = low pKa

Question 2

For a base:

When pH > pKa

Answer 2

more basic environment therefore less H+, so more of the molecule will be deprotonated (neutral form)

Question 3

For a base:

When pH < pKa

Answer 3

More acidic environment therefore more H+, so more of the molecules will be protonated (cation)

Question 4

Aliphatic amines

Type of base?
pKa?
Ionisation?
Formulation in drugs?

Answer 4

Strong base - mostly tertiary or secondary

pKa 9-10

Protonated at physiological pH 7.4 & 2

Formulated as ammonium cation SALTS

Question 5

Aromatic amines

Type of base?
pKa?
Ionisation?

Answer 5

Weak base

pKa 5

Neutral at 7.4, protonated at pH 2

Lone pair on the nitrogen is delocalised around the ring, also resonance onto C=O

Question 6

Guanidines

Type of base?
pKa?
Ionisation?

Answer 6

Very strong base - 3 N’s

pKa 14.5

Protonated at 2 & 7.4

Protonation at =NH:
Resonance - shared positive charge

Found in side chain of Arginine (amino - always a cation) - able to interact with natural/drug ligands in protein active sites

Question 7

Advantage of formulating as a salt?

Answer 7

1. More soluble in water
2. More stable - avoids oxidation on the nitrogen
3. Easier to formulate to give as a medicine in a crystal/powder form (than an oil)

Question 8

What is a heterocycle?

Answer 8

Cyclic compound in which one or more of the atoms in the ring is a heteroatom i.e. not a carbon atom

Typically N, O & S (can also be Se, P, Si, B & As)

e.g. omeprazole, loratadine, Valium

Question 9

What is an alkaloid?

Answer 9

Class of natural product that contains at least one nitrogen heteroatom

e.g. caffeine, serotonin, nicotine