L48- Drug solubility 2 Flashcards
why hydrolysis of carbonyls?
• Drug degradation, e.g. by hydrolysis can lead to: • Inactive medicines • Toxic decomposition products
what is used to attack in nucleophilic addition?
a nucleophile with lone par of electrons
what is used to attack in electrophilic addition?
an oxygen with a lone pair attacks species which is positively charged
explain the reactivity of a carbonyl group?
-the oxygen is more electronegative than the carbon therefore the electrons are not shared equally -the C-O bond is polarised -being shown through resonance form.
explain an addition-elimanation on a carbonyl group?
-must come from the anti-bonding side
explain base promoted ester hydrolysis to form a carboxylate salt and alcohol?
explain an amide hydrolysis to form an amine and carbolate salt?
explain acid catalysed ester hydrolysis?
AASPEN
Why is hydrolysis important?
Drug Synthesis
Drug Stability
Drug mode of action
Pharmacokinetics
explain amides vs ester hydrolysis?
- both function groups have lone pairs of electrons that are in conjugation with the carbonyl.
- the amide is less reactive and is more elctron poor therefore the nitrogen is less elctronegative.
- This means the lone pairs are held less tightly to the nitrogen compared to the lone pairs on the oxygen on the esters, therefore the lone pair of electrons are released into the conjugated system more in the amide.
- the ester has a reduced eectron donation due to it being more electronegativie
what is the importance of hydrolysis with prodrugs?
- Prodrugs are compounds which are inactive in themselves, but which are converted in the body to the active drug.
- Many prodrugs are converted in the body to the active form via hydrolysis.
why is asprin a good prodrug?
- because there is no exposed phenol in it as it causes gastric bleeding
- it is hydrolysed later to give free drug
