Hydrolysis and Oxidation Flashcards
Hydrolysis of esters and lactones
-produce carboxylic acid and alcohol
Hydrolysis of carboxylic acid in basic conditions
-OH nucleophillic attack
-kick out OR
-negative carbox acid + HOR
Hydrolysis of carboxylic acid in acidic conditions
-water attacks carbon
-both products neutral
Aspirin Hydrolysis
-salicylic acid + acetate
-vinegar odor
-acetylate COX to prevent strokes
Lactones
-cyclic esters
-hydrolysis opens ring
-GBL
=hydroxy acid
GBL hydrolysis
-opens 5 membered ring
-prodrug
-converted to active GHB in body
Prevention of ester/lactone hydrolysis
-no moisture (tablets, capsules)
-no heat
-control pH
Hydrolysis of amides and lactams
carboxylic acid + amine
Amides
-peptide bonds
- O=C-NR2
-more stable than ester
-need heat for hydrolysis
ProcainAMIDE hydrolysis
-antiarrhythmic agent
-anesthetic with ester in place of amide
Lactams
-cyclic amides
-penicillin (beta)
-ring-opened amino acids
penicillin hydrolysis
-B-lactam antibiotic
-diff R groups
-hydrolyze LACTAM faster tha AMIDE
Cephalosporins
6 C ring B-lactam
Prevention of hydrolysis of amides and lactams
-NO moisture
-No heat
-control pH
Oxidation redox reaction
reduced <–> oxidized + ne-
-loss of electrons
Promotion of oxidation reactions
exposure to:
-oxygen
-metal ions
-light
-heat
Types of oxidation
-auto
-chain (explosion) (free radical)
Auto-oxidation
-uncatalyzed oxidation of drug by O2
-triplet oxygen (3O2)
-maybe initiation step in chain oxidation
-slower than chain oxidation
Auto-oxidation of Captopril
-ACE inhibitor
-treat HTN and CHF
-catalyzed by metal ions
-also undergoes amide hydrolysis but thats slow loser
Chain Oxidation
- initiation
- propogation
- termination
chain oxidation: Initiation
-generation of free radicals by:
-auto oxidation
-exposure to heat, light, metal ions
chain oxidation: propagation
-reaction of free radicals with oxygen with generation of new free radicals
chain oxidation: termination
-recombination of free radicals to stable products
initiation mechanism
X* + RH –> R* + XH
propagation mechanism
R* + O2 –> ROO*
ROO* + RH –> ROOH + R*
Termination mechanism
ROO* + ROO*
ROO* + R*
R* + R*
all lead to stable product
oxidizable functional groups
-alkenes
-aromatic grps
-ethers
-thioethers
-amines
-carboxylic acids
-nitrites
-aldehydes
Oxidation of Hydroquinone
HydroQ –(Cu2+ –> Cu1+)–> SemiQ –(3O2 –> O2*-)–> BenzoQ
reduction
gain electron
superoxide
O2*-
Hydroquinone
-sunscreen and skin whitening
-prob carcinogen
Hydroquinone toxicity concerns
-OH* radical generated from superoxide
Photolysis
-degradation due to light exposure
-often oxidative
-light can be initiator in chain oxidation
Photolysis of hydroquinone
-first steps same a as oxidation
-polymeric products can be formed
-tetrahydroxybiphenyl
tetrahydroxybiphenyl
-oxidation product linking 2 HQ molecules
Prevention of Oxidation and Photolysis
-protect from oxygen (with nitrogen)
-no heat
-no light
-anti-oxidants
-metal chelators (EDTA)
Minimization of oxidation
-protect from air, light, metal
-add excipients (EDTA)
