Oxygen The Good, the Bad,

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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
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• 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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H2O2 O2.- Reactive oxygen species ROSs
(CH2O)n
Eo(pH 7)
1e-
-0.45 volts
O2 e- O2.-
Energy
2e-
0.30 V
O2 2H 2e- H2O2
4e-
0.82 V
O2 4H 4e- H2O
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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.- O2.- 2H
  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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Physiological Reactive Oxygen Species

• O2.- and H2O2 released as respiration
  by-products, H2O2 10-7 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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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 - Parkinsons
• - Alzheimers diseases

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Moderation of Physiological ROSs
Radical scavenging
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Antioxidants - chemopreventives

• SA flavonoids are plant products
• Flavonoids
• highly colored
• grapes - red wine
• chocolate
• teas
• 200-400 varieties

• Chemical mechanism of action

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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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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 1995. V 15
mg Mo 10 mg Co 1.2 mg Physiological
Systems must control pro-oxidant metals Storage
and Transport of Fe. - Redox Deactivation Anim
als (Humans) - Ferritin, Transferrin Plants
Bacteria - Siderophores
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apoenzyme
Free Fe
Citrate ADP/ATP DNA proteins
Low molecular weight Fe
White Blood Cells
H2O2
Oxidative burst
O2
HO
Incomplete metabolism
H2O2
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Cyclic Voltammetry of FeII/III EDTA in the
Absence and Presence of H2O2
B
1.0 uA
A
0.4 uA
- 0.7
Potential vs. Ag/AgCl
Electrode FeIII(EDTA) e FeII(EDTA) E -
0.090 volts SHE Solution FeII(EDTA) H2O2
FeIII(EDTA) HO- HO.
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apoenzyme
Inert iron complexes
Salicylateflavonoids
Free Fe
Citrate ADP/ATP DNA proteins
Low molecular weight Fe
White Blood Cells
H2O2
Oxidative burst
O2
HO
Incomplete metabolism
H2O2
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Summary salicylate studied flavonoids have
common features - metal chelation -
quantitative structure-activity
relationships
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Bidentate chelation site
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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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Other anti-inflammatory agents

• All of the following NSAIDs are iron chelation
  agents.
• Iron chelation may play a role in their medicinal
  action.

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The Ugly - Halocarbon/nitroaromatic pollutants
PCB
DDT
PCP
TNT

• Nerve agents
• Method for disposal

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Present method of disposal - Incineration gt
1200 0C - CxHyClz O2 CO2 H2O
HCl (unbalanced)
Problems - Costs (incineration and
transport) - PCDFs PCDs - NIMBY
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• Preferences
• Inexpensive
• Safe
• Transportable
• Environmentally Benign
• Acceptable to NIMBY

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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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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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H2O2
O2 2H

EDTA
Iron particles 0.1-1 mm
FeIIEDTA
Fe2
FeIIIEDTA HO- HO.
pollutant
CO2 H2O
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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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Other Interests... Chemical Mechanisms of O2
Evolution from Plants Chemical Analyses of PCB,
PCP, DDT Electrochemical Detectors Lead-Acid
Battery