1. Oxygen – The Good, the Bad, & the Ugly
The Good - Biological Oxidant O2
The Bad - Damage to Biological Systems by
Partially Reduced Oxygen
The Ugly - Oxidation of Pollutants

2. Oxygen - The Bad Partially reduced oxygen species in metabolism
Reactive Oxygen Species
Physiologic Damage to Proteins, Fatty Acids, DNA
ROS theory of aging
Antioxidants - Moderation of Damage by ROS
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3. 1e- Energy 2e- 4e- (CH2O)n Eo’(pH 7) -0.45 volts O2 + e- = O2.-
H2O2 & O2.- = “Reactive oxygen species” ROSs
(CH2O)n
Eo’(pH 7)
1e-
-0.45 volts
O2 + e- = O2.-
Energy
2e-
O2 + 2H+ + 2e- = H2O2
0.30 V
4e-
0.82 V
O2 + 4H+ + 4e- = H2O
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4. Dangers of Reactive Oxygen Species
*Hydrogen peroxide
* Fenton Reaction H2O2 + FeII = FeIII + HO- +
HO. + e- = HO- Eo = 1.8 volts
*Superoxide ion
* Disproportionation to H2O O2.- + O H+ = H2O2 + O2
* Reducing agent for Fenton rxn. O2.- + FeIII(L)n = FeII(L)n + O2
* Reduces Fe3+(insoluble) to Fe2+ (soluble) HO
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5. Physiological Reactive Oxygen Species
O2.- and H2O2 released as respiration by-products, [H2O2] = [O2.-] = 10-11
Also, inflammation response (pathogen defense) by white blood cells (phagocytes)
Physiological oxidative damage linked to chronic inflammation (auto-immune)
Other ROSs
Hypochlorous Acid
H2O2 + Cl-  HOCl + HO-
Peroxynitrite (RNS)
NO + O2.-  ONOO.-
HO.
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6. Hydroxyl Radical Damage to Physiology Results in .....
Denaturation of lens proteins - cataracts
DNA strand breakage - damage to genes
- cancers mitochondrial dysfunction
- aging
Fatty acid cross linking - circulatory diseases
Damage to nervous system - Parkinson’s
- Alzheimer’s diseases
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7. Moderation of Physiological ROSs
Radical scavenging
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8. Antioxidants - chemopreventives
Flavonoids
SA & flavonoids are plant products
Flavonoids
highly colored
grapes - red wine
chocolate
teas
varieties
Chemical mechanism of action
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9. Antioxidant Action(s) of Aspirin & Flavonoids
1. Acts a chemopreventive agent
flavonoids and aspirin (and aspirin-like drugs) prevent
many diseases associated with oxidative damage.
Free Radicals in Biology and Medicine 9, (1990) 299.
2. Acetylation mechanism cannot explain anti-inflammatory action
salicylic acid = aspirin
many flavonoids have anti-inflammatory action
* Hypothesis for molecular base action of antioxidant action
Chelation of pro-oxidant metal ions………...Iron
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10. Metal Chelation Hypothesis
* Many transition metals are pro-oxidants
per 75 kg human
Fe 4.5 g Biocoordination Chemistry, David Mn 1 g E. Fenton Oxford University Press, Cu 100 mg
V 15 mg
Mo 10 mg
Co 1.2 mg
* Physiological Systems must control pro-oxidant metals
Storage and Transport of Fe. - Redox Deactivation
Animals (Humans) - Ferritin, Transferrin
Plants & Bacteria - Siderophores
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11. O2 HO· H2O2 H2O2 White Blood Cells Oxidative burst Incomplete
apoenzyme
Free Fe
Citrate
ADP/ATP
DNA
proteins
Low
molecular
weight Fe Fe
containing
enzymes
White
Blood
Cells
H2O2
Oxidative burst O2
HO·
Incomplete
metabolism
H2O2 Fe
containing
enzymes
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12. Cyclic Voltammetry of FeII/III [EDTA] in the Absence and Presence of H2O2
1.0 uA A
0.4 uA
- 0.7
Potential vs. Ag/AgCl
Electrode: FeIII(EDTA) + e = FeII(EDTA) E = volts SHE
Solution: FeII(EDTA) + H2O2 = FeIII(EDTA) + HO- + HO.
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13. Figure 2. 3. 2) Moderation of the Fenton reaction characteristic of 0
Figure 2.3.2) Moderation of the Fenton reaction characteristic of 0.25 mM FeIIIATP, 8.6 mM H2O2 in M HEPES buffer pH 7.4 by quercetin. The cyclic voltammograms (left) were taken at 20 mV/s for the various quercetin/iron ratios. The quercetin/FeIIIATP ratios (I-VII) are indicated on the x-axis of the righthand graph. The catalytic wave at volts are plotted versus the quercetin/iron ratio in the bottom graph. The current of point VII at –0.400 volts is the same as the background current (0.00 mM H2O2)
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14. O2 HO· H2O2 H2O2 Inert iron complexes White Blood Cells
apoenzyme
Inert
iron
complexes
Salicylate+flavonoids
Free Fe
Citrate
ADP/ATP
DNA
proteins
Low
molecular
weight Fe Fe
containing
enzymes
White
Blood
Cells
H2O2
Oxidative burst O2
HO·
Incomplete
metabolism
H2O2 Fe
containing
enzymes
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15. salicylate & studied flavonoids have common features - metal chelation
Summary
salicylate & studied flavonoids have common features
- metal chelation
- quantitative structure-activity relationships
Flavonoids
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16. Bidentate
chelation site
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17. Rules 1 and 2 may imply metal chelation as an important action.
Quantitative Structure-Activity Relationships (QSAR) for Salicylates and Derivatives (Anti-inflammatory action)
Rule 1. Substitution on either the carboxyl or the phenolic hydroxyl groups affect activity.
Rule 2. Placing the phenolic hydroxyl group meta or para to the carboxyl group abolishes activity.
Rule 3. Substitution of halogen atoms on the aromatic ring enhances potency.
Rule 4. Substitution of aromatic rings meta to the to the carboxyl and para to the phenolic hydroxyl groups increases anti-inflammatory activity.
Rules 1 and 2 may imply metal chelation as an important action.
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18. Other anti-inflammatory agents
All of the following NSAID’s are iron chelation agents.
Iron chelation may play a role in their medicinal action.
N-ayrlanthranilic Acids C O N H 2 R 1 3 M e f n a m i c A d , = l o F u S P r x I t h
Salicylamide
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19. The Ugly - Halocarbon/nitroaromatic pollutants
PCB
DDT
PCP
TNT
Nerve agents
Method for disposal
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20. Present method of disposal
- Incineration > C
- CxHyClz + O2 = CO2 + H2O + HCl (unbalanced)
Problems:
- Costs (incineration and transport)
- PCDFs PCDs
- NIMBY
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21. Preferences Inexpensive Safe Transportable Environmentally Benign
Acceptable to NIMBY
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22. Ideal Characteristics for Pollutant Destruction Reactions
-Complete mineralization, i.e. CO2
- Mild reaction conditions, i.e. room temperature & pressure
- Inexpensive reagents
Other investigators:
-UV radiation - TiO2 -Sonochemical
-H2O2 oxidation -Electrochemical oxidation - reductions
What about air?
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23. O2 is kinetically stable
-Requires “activation”, partially reduced oxygen.
-Scheme:
O2(air) + 2H+(aq) + 2e- = H2O2
-Zero-valent iron, Fe(0)
Inexpensive
Spent agent, Fe2+/Fe3+ environmentally benign.
Chelated forms, capable oxidizing agents
Chemical reducing agent
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24. H2O2 + Iron particles 0.1-1 mm pollutant CO2 + H2O Fe2+ O2 + 2H+ EDTA
FeIIEDTA
FeIIIEDTA + HO- + HO.
pollutant
CO2 + H2O
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25. - First known example of room temperature & pressure activation of O2
Summary
- 80% CO2 yields for chlorinated phenols, complete destruction of
PCB, PCP, DDT, nitrophenols
- First known example of room temperature & pressure activation of O2
to a form that can oxidized organics to CO2.
- Inexpensive reagents, air, iron particles, water, EDTA.
-PCDFs, PCDs not detected (to the D.L. GC-ECD, 1 ppb)
-Unspecialized reactors, transportable technology.
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26. Chemical Mechanisms of O2 Evolution from Plants
Other Interests……...
Chemical Mechanisms of O2 Evolution from Plants
Chemical Analyses of PCB, PCP, & DDT
Electrochemical Detectors
Lead-Acid Battery
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