Hydrolysis and Oxidation

Question 1

Hydrolysis of esters and lactones

Answer 1

-produce carboxylic acid and alcohol

Question 2

Hydrolysis of carboxylic acid in basic conditions

Answer 2

-OH nucleophillic attack
-kick out OR
-negative carbox acid + HOR

Question 3

Hydrolysis of carboxylic acid in acidic conditions

Answer 3

-water attacks carbon
-both products neutral

Question 4

Aspirin Hydrolysis

Answer 4

-salicylic acid + acetate
-vinegar odor
-acetylate COX to prevent strokes

Question 5

Lactones

Answer 5

-cyclic esters
-hydrolysis opens ring
-GBL
=hydroxy acid

Question 6

GBL hydrolysis

Answer 6

-opens 5 membered ring
-prodrug
-converted to active GHB in body

Question 7

Prevention of ester/lactone hydrolysis

Answer 7

-no moisture (tablets, capsules)
-no heat
-control pH

Question 8

Hydrolysis of amides and lactams

Answer 8

carboxylic acid + amine

Question 9

Amides

Answer 9

-peptide bonds
- O=C-NR2
-more stable than ester
-need heat for hydrolysis

Question 10

ProcainAMIDE hydrolysis

Answer 10

-antiarrhythmic agent
-anesthetic with ester in place of amide

Question 11

Lactams

Answer 11

-cyclic amides
-penicillin (beta)
-ring-opened amino acids

Question 12

penicillin hydrolysis

Answer 12

-B-lactam antibiotic
-diff R groups
-hydrolyze LACTAM faster tha AMIDE

Question 13

Cephalosporins

Answer 13

6 C ring B-lactam

Question 14

Prevention of hydrolysis of amides and lactams

Answer 14

-NO moisture
-No heat
-control pH

Question 15

Oxidation redox reaction

Answer 15

reduced <–> oxidized + ne-

-loss of electrons

Question 16

Promotion of oxidation reactions

Answer 16

exposure to:
-oxygen
-metal ions
-light
-heat

Question 17

Types of oxidation

Answer 17

-auto
-chain (explosion) (free radical)

Question 18

Auto-oxidation

Answer 18

-uncatalyzed oxidation of drug by O2
-triplet oxygen (3O2)
-maybe initiation step in chain oxidation
-slower than chain oxidation

Question 19

Auto-oxidation of Captopril

Answer 19

-ACE inhibitor
-treat HTN and CHF
-catalyzed by metal ions
-also undergoes amide hydrolysis but thats slow loser

Question 20

Chain Oxidation

Answer 20

1. initiation
2. propogation
3. termination

Question 21

chain oxidation: Initiation

Answer 21

-generation of free radicals by:
-auto oxidation
-exposure to heat, light, metal ions

Question 22

chain oxidation: propagation

Answer 22

-reaction of free radicals with oxygen with generation of new free radicals

Question 23

chain oxidation: termination

Answer 23

-recombination of free radicals to stable products

Question 24

initiation mechanism

Answer 24

X* + RH –> R* + XH

Question 25

propagation mechanism

Answer 25

R* + O2 –> ROO*
ROO* + RH –> ROOH + R*

Question 26

Termination mechanism

Answer 26

ROO* + ROO*
ROO* + R*
R* + R*

all lead to stable product

Question 27

oxidizable functional groups

Answer 27

-alkenes
-aromatic grps
-ethers
-thioethers
-amines
-carboxylic acids
-nitrites
-aldehydes

Question 28

Oxidation of Hydroquinone

Answer 28

HydroQ –(Cu2+ –> Cu1+)–> SemiQ –(3O2 –> O2*-)–> BenzoQ

Question 29

reduction

Answer 29

gain electron

Question 30

superoxide

Answer 30

O2*-

Question 31

Hydroquinone

Answer 31

-sunscreen and skin whitening
-prob carcinogen

Question 32

Hydroquinone toxicity concerns

Answer 32

-OH* radical generated from superoxide

Question 33

Photolysis

Answer 33

-degradation due to light exposure
-often oxidative
-light can be initiator in chain oxidation

Question 34

Photolysis of hydroquinone

Answer 34

-first steps same a as oxidation
-polymeric products can be formed
-tetrahydroxybiphenyl

Question 35

tetrahydroxybiphenyl

Answer 35

-oxidation product linking 2 HQ molecules

Question 36

Prevention of Oxidation and Photolysis

Answer 36

-protect from oxygen (with nitrogen)
-no heat
-no light
-anti-oxidants
-metal chelators (EDTA)

Question 37

Minimization of oxidation

Answer 37

-protect from air, light, metal
-add excipients (EDTA)