Chapter 3 Flashcards
What is the ionization constant pKa?
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
Under which condition will an acid donate its proton?
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
Which pKa is preferred to prevent GI irritation?
A higher pKa -> weaker acid
The lower the pKa, the stronger the acid and the more stable its conjugate base
Why is Phenol a weak acid?
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
What are the common features among acidic functional groups?
-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
Examples of acidic functional groups:
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)
What is the term for the ionized form of Carboxylic acid?
Carboxylate
Why can acidic drugs be irritating to the stomach?
Because of the acidic functional group and the high potential to be ionized (donation of H) under GI conditions (low pH), a buffer needed
Why is beta-dicarbonyl/imide considered an acid?
(one of the few examples where a carbon donates a proton)
- It has a proton to donate
- it can stabilize the resulting negative functional group
Why is Sulfonamide considered an acid?
Because when nitrogen kicks off the proton, it can be stabilized by the sulfoxide
Why are Sulfonamides weaker acids than acids with -COOH
Because they have a higher pKa and are harder to ionize,
-> on the other side also less irritating to the stomach
What is an isosteric replacement?
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
What is a Tetrazol?
5-membered ring with 4 nitrogens -> acidic
1. can donate its H
2. Stabilize its self within the ring
What are the common features of basic functional groups?
-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
Examples of basic functional groups:
Amines, Imines, Hydrazines, Amidines, Guanidines, Heterocyclic nitrogens
What are ionized aliphatic amines called? (have a lone pair)
aliphatic: no ring structure, but chain form
Amino
Basic functional groups often have N in their structure,
which Nitrogen containing structure is an acid?
Tetrazole, Sulfon urea
How are aromatic amines/anilines different from aliphatic amines?
(aniline: 1° amine on phenyl ring, 1x R)
-The amine group is directly attached to a phenyl ring
-less basic bc their pKa is low -> hard to ionize
How are imines different from amines?
-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
Why are amides not considered basic, even though their N has a lone pair?
Because the lone e- pair serve to stabilize the structure (carbonyl), and not to attract a proton
What does the structure of Amidine look like?
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
What does the structure of Guanidine look like?
Delocalization between three or more nitrogens, even more electrons as an attractor force for protons -> high pKa 12-13
Examples of nitrogen being acidic, basic, or neither of those
Acidic: Sulfonurea
Basic: Amines, Imines, Hydrazines, Amidines, Guanidine
Neither: Amide
What heterocyclic nitrogens?
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
What does amphoteric mean and how is it different from a zwitterion?
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
What is an example of an amphoteric drug?
Sulfamethoxazole: it has a (basic) aromatic amine and an (acidic) sulfonamide
