Chapter 3

Question 1

What is the ionization constant pKa?

Answer 1

used to compare the strength of an acid or base, based on the pH conditions -> predict what behavior of acids and bases -> f.e if an acid will donate his H

Question 2

Under which condition will an acid donate its proton?

Answer 2

When the pH is lower (the environment is more acidic) than the pKa, the acid will keep its proton, bc there is nothing that promotes the donation -> an acid needs a more basic pH (environment) than its pKa

when the pH is higher (more basic) than the pKa the acid will donate its proton

Question 3

Which pKa is preferred to prevent GI irritation?

Answer 3

A higher pKa -> weaker acid

The lower the pKa, the stronger the acid and the more stable its conjugate base

Question 4

Why is Phenol a weak acid?

Answer 4

Because its pKa is 10, under acid conditions (low pH) it will still not donate its proton until the pH exceeds the pKa of 10

-the oxygen is electronegative and will tend to attract the hydrogen ion back again

Question 5

What are the common features among acidic functional groups?

Answer 5

-They have a proton to donate (if the pH is right)

-They can stabilize the resulting negative functional group
(f.e. -CH3 -> -CH2 is not considered acid bc it cant stabilize itself

Question 6

Examples of acidic functional groups:

Answer 6

Carboxylic acid, ß-dicarbonyl / imide, Sulfonamide and Sulfonylurea, Tetrazol, Phenol (very weak, doesn’t work as acid under physiological condition bc pKa is so high)

Question 7

What is the term for the ionized form of Carboxylic acid?

Answer 7

Carboxylate

Question 8

Why can acidic drugs be irritating to the stomach?

Answer 8

Because of the acidic functional group and the high potential to be ionized (donation of H) under GI conditions (low pH), a buffer needed

Question 9

Why is beta-dicarbonyl/imide considered an acid?
(one of the few examples where a carbon donates a proton)

Answer 9

1. It has a proton to donate
2. it can stabilize the resulting negative functional group

Question 10

Why is Sulfonamide considered an acid?

Answer 10

Because when nitrogen kicks off the proton, it can be stabilized by the sulfoxide

Question 11

Why are Sulfonamides weaker acids than acids with -COOH

Answer 11

Because they have a higher pKa and are harder to ionize,
-> on the other side also less irritating to the stomach

Question 12

What is an isosteric replacement?

Answer 12

Used in drug development to replace f.e. one acidic functional group to make the whole structure less acidic, but is now less offensive -> the other acidic group(s) cant be replaced bc they are needed to interact with the target - the drug won’t work without them

Question 13

What is a Tetrazol?

Answer 13

5-membered ring with 4 nitrogens -> acidic
1. can donate its H
2. Stabilize its self within the ring

Question 14

What are the common features of basic functional groups?

Answer 14

-They often have nitrogens (doesn’t necessarily mean it’s basic)
-lone pair on the nitrogen that can accept protons
-They become positive when ionized

Question 15

Examples of basic functional groups:

Answer 15

Amines, Imines, Hydrazines, Amidines, Guanidines, Heterocyclic nitrogens

Question 16

What are ionized aliphatic amines called? (have a lone pair)
aliphatic: no ring structure, but chain form

Answer 16

Amino

Question 17

Basic functional groups often have N in their structure,
which Nitrogen containing structure is an acid?

Answer 17

Tetrazole, Sulfon urea

Question 18

How are aromatic amines/anilines different from aliphatic amines?
(aniline: 1° amine on phenyl ring, 1x R)

Answer 18

-The amine group is directly attached to a phenyl ring
-less basic bc their pKa is low -> hard to ionize

Question 19

How are imines different from amines?

Answer 19

-The pKa is lower -> less basic -> harder to ionize
this is bc the N is in a conjugated ring making it harder to be ionized

-seen in Benzodiazepines and anti-viral drugs

Question 20

Why are amides not considered basic, even though their N has a lone pair?

Answer 20

Because the lone e- pair serve to stabilize the structure (carbonyl), and not to attract a proton

Question 21

What does the structure of Amidine look like?

Answer 21

Like an Imine, but there is another N, the positive charge can be delocalized between the 2 nitrogen
bc of the second N the whole system becomes more of an attractor for protons - pKa: 10-11

Question 22

What does the structure of Guanidine look like?

Answer 22

Delocalization between three or more nitrogens, even more electrons as an attractor force for protons -> high pKa 12-13

Question 23

Examples of nitrogen being acidic, basic, or neither of those

Answer 23

Acidic: Sulfonurea
Basic: Amines, Imines, Hydrazines, Amidines, Guanidine
Neither: Amide

Question 24

What heterocyclic nitrogens?

Answer 24

Heterocyclic means a ring with at least an atom other than C
-> here nitrogen

-they vary in basicity and are less basic than aromatic amines
bc the lone pair can resonate in the ring structure and it is harder for the proton to attach to the lone pair of N in the ring structure

Question 25

What does amphoteric mean and how is it different from a zwitterion?

Answer 25

Amphoteric: a structure has at least one acidic and one basic functional group

Zwitterion: has one ionized (charged) acidic and one ionized basic functional group

Question 26

What is an example of an amphoteric drug?

Answer 26

Sulfamethoxazole: it has a (basic) aromatic amine and an (acidic) sulfonamide