Ionising Groups in Drugs - Acids Flashcards
What type of molecule will be cleared in the urine?
An ionised/polar molecule because they are water soluble.
What type of molecule can be absorbed from the gut?
An unionised/non-polar/neutral molecule because they are lipid soluble and can cross biological membranes.
What state of ionisation is more likely to bind to a receptor?
Ionised
Usual range of pKa values for drugs? Why?
between 3-10
This means there will be some ionised (water soluble) forms and some neutral (membrane soluble) forms at pH 7.4 (physiological pH)
What is pKa?
The pH at which the acid is the 50% ionised
pKa rule for acids - why?
The smaller the pKa the stronger the acid - more likely to ionise/deprotonate
Acids:
What happens when pH > pKa
Why?
If pH is greater, then the environment is more basic (less H+), so the acid is more likely to deprotonate to maintain equilibrium. Therefore there will be more of the ionised (anion) form present.
Acids:
What happens when pH < pKa
Why?
If pH is lower than the pKa, then the environment is more acidic (there is a high concentration of H+). Therefore the acid would remain fully protonated (neutral).
Which acidic functional groups are present in drug structures?
- Carboxylic acids
- Sulfonamides
- Phenols
- Enols
Carboxylic Acids (-COOH)
pKa?
Type of acid?
Ionisation in blood?
Between 3.5-5
‘Strong acid’ - also stabilised by resonance.
Always ionised at pH 7.4
Sulfonamides (R-SO2NH2 and R-SO2NHR)
Acid action?
Resonance?
NH is acidic - becomes N-
Stabilised by 3 resonance structures - pushes electrons to S=O bonds
It is a low energy stabilised anion
Present in many drug structures e.g. antibacterials
Amides?
Do not ionise under physiological conditions - always neutral
Phenols/Aromatic alcohols
pKa?
Type of acid?
Ionisation?
Resonance?
Aliphatic alcohols?
pKa 10
Weakly acidic
Neutral at pH 2 and 7.4
Stabilised by 4 resonance structures - not stable
Alcohols are not acidic
