Antioxidant:

An Agent that prevents or inhibits oxidation. Antioxidants are substances that may protect cells from the damaging effects of oxygen radicals, highly reactive chemicals that play a part in atherosclerosis, some forms of cancer, and reperfusion injuries

Atherosclerosis (ather-oshle-rosis) is where cholesterol-lipid-calcium deposits in the walls of the arteries.

General Mechanisms of Autoxidation

C H3 (C H2)3 14 13 12 11 10 9 C H2 C H C H C H2 C H C H -H 12 C H3

C H2 R

INITIATION (METAL) 11 10 ( C H 2) 4 C H C H C H

9 C H2 R

CH CH

+ O2

C H3

(C H2)4 C H C H C H C H C H O
12

C H2 R
10 9

11 +H

PROPAGATION

CH3

12 11 10 (CH2)4 CH CH CH CH CH - OH

CH2

O HYDROPEROXIDE DECOMPOSION O H CH (C H )

2 4

12 11 CH CH CH O

10 9 CH CH

CH

O C H3 ( C H 2) 3 CH2

+ H

12 CH

11 CH

10 CH

9 CH

C H2

TERMINATION C H3 ( C H 2) 3

+ H C H 3 (PENTANE)

Triplet Oxygen Oxidation

Molecular Orbital of Triplet Oxygen

Molecular
*

Atomic
* *

Atomic

2Px 2Py 2Pz

2Pz 2Py 2Px

Energy 2S

* *

2S

1S

1S

Initiation of Triplet Oxygen Oxidation

Initiation of autoxidation occurs when hydrogen atom at -methylene group in double bonds is removed to form an alkyl radical (R ).

CH3

(CH2)4 CH CH CH2 CH CH (CH2)7 COOH

RH

Propagation
R

O2

ROO

ROO +
ROOH

RH

ROOH + R
RO ROH + +

OH

RO + RH

Termination
R

R-R ROO R ROOR ROR ROOR + O2

2RO ROO + RO + R

ROO + ROO

Singlet Oxygen Oxidation

Molecular Orbital of Singlet Oxygen

Molecular
*

Atomic

Atomic

2Px 2Py 2Pz

Energy

2Pz 2Py 2Px

2S

2S
*

1S

1S

Singlet Oxygen Formation

Enzyme s

RCOO + RCOO
Endoperoxide s Ozone

O2 + Sensitizer H2O2 + OCI-

O2

H2O2 + O2 -

OH- + O2 H2O2+ HO2 O 2 - + O2 O2 -

O2 - + Y+

Reaction of 3O2 and 1O2 with Linoleic Acid

OH O R
Conjugated

3O

R
- H

R '

R '

R '

3O

HOO R R '
Conjugated

R '

OH O
R
1O

R O' H O

R
Conjugated

R '

R '

OH O

R' O OH

' R

Nonconjugated

Function of Antioxidant on Lipid Oxidation

Inhibits or slows the formation of free alkyl radicals in the initiation step Interrupts the propagation of free radical chain Delays the start or slows the chemical reaction rate of lipid oxidation.

Types of Antioxidants
Hydrogen donating compounds
Singlet oxygen quenchers Metal chelators

Enzymes
Oxygen scavengers

Hydrogen Donating Antioxidant

Should have lower reduction potential than the reduction potential of polyunsaturated fattyacid (E = 600 mV) Should donate a hydrogen to alkoxyl (E =1600mV) or peroxyl (E= 1000 mV) radicals

Characteristics of Hydrogen Donating Antioxidants

The major hydrogen donating antioxidants are monohydroxy or polyhydroxy phenolic compounds with various ring substitutions. The antioxidant free radical does not initiate another free radical due to the stabilization of radical by delocalization.

Effectiveness of Antioxidants
1. The difference of one-electron reduction potential between lipid radical and antioxidant radical. 2. The stability of antioxidant radical. The resonance delocalization Further oxidation of antioxidant radicals

Synthetic Antioxidants
OH C(CH3)3
(CH3)3C

OH
C(CH3)3

OCH3
Butylatedhydroxyanisole (BHA)
OH

CH3

Butylatedhydroxytoluene (BHT)
OH C ( C H 3 )3

OH

OH
OH

COOC H

3 7

Propyl gallate

Tertiary butylhydroquionone (TBHQ)

Tocopherols
R1 HO CH3 R2 R3 O CH3 CH3 CH3 CH3

Trivial Name
-Tocopherol -Tocopherol -Tocopherol -Tocopherol

Chemical Name
5,7,8-Trimethyltocol 5,8-Dimethyltocol 7,8-Dimethyltocol 8-Methyltocol

R1
CH3 CH3 H H

R2
CH3 H CH3 H

R3
CH3 CH3 CH3 CH3

Ascorbic Acid
Hydrogen donation to lipid radicals
Quenching of singlet oxygen

Removal of molecular oxygen

Regenerate tocopherol radicals

Prooxidant

Reduce ferric iron to ferrous iron

Ascorbic Acid

CH2OH

H C OH O
H HO

-H

CH2OH H C OH O H

CH2OH O

-H

H C OH O H

OH

R, RO , ROO

R , RO , ROO

HO

L-Ascorbic acid

Dehydroascorbic acid

Metal Chelators
Phosphoric acid
Citric acid Ascorbic acid Ethylene Diamine Tetra Acetate (EDTA) Amino acids and peptides

Proteins such as transferrin, ovotransferrin

Prooxidant Mechanisms of Metals

Hydroperoxide decomposition to form peroxyl radical and alkoxyl radical.
Fe3+ + ROOH Fe2+ + ROO + H+

Fe2+ +

ROOH

Fe3+ + RO + OH

Interaction of Chealator and Metal

O O C O M O C O O N CH2 C O C H2 CH2

N
CH2 CH2 CH2

C
O

Ethylene Diamine Tetra Acetate (EDTA)

Antioxidant Sources

Flavonoids
OH

OH HO

OH O

OH

HO

OH OH O
OH

O Glucoside

Quercetin Flavonols

Cyanidin-3-glucoside Anthocyanins

Flavonoids
Secondary products of plant metabolism Metal chelating ability Superoxide anion scavengers Hydrogen donors
Anthocyanines, catechins, flavones, flavonols, isoflavone, and proanthocyanidins

Vegetables

Cacao beans, Potato, Tomato, Spinach, Legumes, Garlic, and Seaweed

Polyphenolic compounds

Fruits

Wines: Anthocyanin Polyphenolic compounds

Tea
O H O H H O O O H O H O H H O O O H O H O H O H

Epicatechin

Epigallocatechin

Sesame Seed
O
O O

O
OH

O H
O H3 C

Sesamol

Sesamolinol

Herb and Spice

Sage, Ginger, Green pepper, Lavender and Rosemary
O H
H O HO OC C3 H C H
3

O H O
H O C O

C3 H C3 H

3 HC

C3 H

3 HC

C3 H

Carnosoic Acid
HO OC O

Carnosol
O H
O H

O H O
O H

Rosemarinic Acid

Soybean
Chlorogenic acid, caffeic acid, ferulic acid Metal chelation and singlet oxygen quenching

Isoflavones Metal chelation and hydrogen donation

Soybean
HO COOH

O
HO OH OH OH O

R2 R1

Chlorogenic acid

OH

Isoflavones R1
Genistein OH Daidzein H

R2
OH OH

Korean Ginseng

Korean Ginseng
CH CH COOH HO OCH3
HO OH

CH CH COOH

Ferulic acid
OH

Caffeic acid
O

COOH HO OCH
OH OH O OH

Vanillic acid

Kaempferol