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LSU Chemistry Department 6/14/05 1
Stable Free Radicals and Potential Implications for Health Effects of Diesel
Emissions
Barry DellingerBarry Dellinger
Department of ChemistryDepartment of Chemistry
Louisiana State UniversityLouisiana State University
11th Annual Diesel Engine Emission Reduction (DEER) Conference11th Annual Diesel Engine Emission Reduction (DEER) ConferenceChicago, IllinoisChicago, Illinois
August 12 August 12 -- 15, 200515, 2005
LSU Chemistry Department 6/14/05 2
Chemical Reaction Zones in a Combustion Device
PersistentRadicals
LSU Chemistry Department 6/14/05 3
Chemical Reaction Zones in an Automotive Engine System
Pre-Flame and Flame Zone
Cool Zone
Post-Flame Zone
LSU Chemistry Department 6/14/05 4
Radical Stabilities/Reactivities
10-6 s 10-3 s103 s100 s
OH
H
O H2C CH
CH3
H
H
HH
H
H2C C CHOH
O
R
RO2PAN
O2
NO
OH
O
NO
LSU Chemistry Department 6/14/05 5
Resonance Stabilized Semiquinone Radicals
OH
OH
O
OH OH
O O
OH- H
LSU Chemistry Department 6/14/05 6
Oxidative Cycles of Semiquinones
OH
OH
O
O_
O
O
NADPH orNADP+ or
AscorbateDehydroascorbate
O2_
H2O2 O2_
HO
Fe2+
Fe3+
Cellular Damage
O2
NADPH or Ascorbate
NADP+ or Dehydroascorbate
LSU Chemistry Department 6/14/05 7
Tobacco Components Producing Radicals
Total Protein
Lignin
LSU Chemistry Department 6/14/05 8
EPR Spectra of Combustion-Generated Particles
LSU Chemistry Department 6/14/05 9
Source Distribution of PM2.5
Adapted from Gray and Cass, 1998
LSU Chemistry Department 6/14/05 10
EPR Spectra of PM2.5 Samples
LSU Chemistry Department 6/14/05 11
Lung Epithelial Cell DamageIncinerator Fly-ash Baton Rouge PM2.55 City PM2.5
LSU Chemistry Department 6/14/05 12
Stabilization Mechanisms
OH
OH
Cu) O
OH
OH
O
CuOO O
OH
H
Physisorption
- H2O
Chemisorption
OH
Cu(II)
O
O
O
e- transfer
RadicalFormation
OH
O.
OH
O
Cu(I)
O O
Cu(I)
O O
.
Mesomerization
LSU Chemistry Department 6/14/05 13
4000 3500 3000 2500 2000 1500
Aromatic ring-breathing1592 and 1493 cm-1
After 1-hour exposure
Cab-O-Sil before dosing
27% reduction inO-H stretching intensity
Isolated SiO-H group3747 cm-1
FTIR Spectra of 2-Chlorophenol on Silica at 350 C
LSU Chemistry Department 6/14/05 14
XANES Spectra of CuO/SilicaReduction by Phenol
8975 8980 8985 8990Photon Energy (eV)
DataBest fit: 3% Cu(0), 45% Cu(I) and 52% Cu(II)3% Cu(0), 55% Cu(I) and 42% Cu(II)3% Cu(0), 35% Cu(I) and 62% Cu(II)
Cu(I)Cu(0)
Cu(II)
Abs
orb a
nce
LSU Chemistry Department 6/14/05 15
Radical Yieldson 5% Cu(II)O/Silica
30025020015010050Adsorption Temperature, oC
1400
1200
1000
800
600
400
200
Spin
s/g
1,2-DichlorobenzeneChlorophenolChlorobenzeneHydroquinoneCatechol
LSU Chemistry Department 6/14/05 16
Radical g-Valueson 5% Cu(II)O/Silica
2.0080
2.0075
2.0070
2.0065
2.0060
2.0055
2.0050
2.0045
g va
lue
35030025020015010050Adsorption Temperature oC
Monochlorobenzene1,2-Dichlorobenzene2-ChlorophenolCatecholHydroquinone
LSU Chemistry Department 6/14/05 17
Substitution Effect on Radical Structure
CuO
Cu(I)
OCl
Cu(II)O
Cu(I)
OHCl
.
Chlorine Substitution
Hydroxyl Substitution
Cu(II)O
Cu(I)
O.HO
Cu(II) Cu(I)
OO
Cu(II)O
Cu(I)
O.O
H
H
HO
LSU Chemistry Department 6/14/05 18
Engineered Nanoparticle Surrogates~5 nm CuO ~30 nm CuO CuO/Carbon
LSU Chemistry Department 6/14/05 19
FMS0.5 suspended in 50 μl sterile, isotonic saline (1μg/μl) were instilled into the lungs of mice. At 24 h, , the mice were euthanized and exsanguinated. Peripheral blood and tissues were isolated. FMS were seen freely floating in the(a,d) peripheral blood (inset: FMS-laden macrophage; (b,e) within the myocardial tissue; and (c,f) within cells of the airways. (a,b,c) Brightfield images. (d,e,f) Fluorescent images: excitation/emission at 560/610 nm. Arrows indicate representative FMS0.5 in tissues. Scale bar = 20μm.
Nanoparticles Diffuse from the Lung into the Blood and Tissues
LSU Chemistry Department 6/14/05 20
A) Standard curve of FMS1 in isotonic saline containing 0.02% tween-80. The FMS1 standard curve was linear from 49 – 1562 particles/ml Mean values ( ) ± Cl plotted (n=3; r2=0.9987). B) Approximately 60%, 7%, and 2% of the total instilled dose was observed in the lungs, heart, and liver; respectively Values in the organs are percentages of the total dose of FMS1 administered to the mouse.
Biodistribution of FMS0.5 30 min After Intratracheal Instillation
LSU Chemistry Department 6/14/05 21
Surrogates Reduce Epithelial (and Myocardial) Cell Viability
5,000 cells/well plated 24 hrs prior to exposure176 ug exposure for 24 hrs3 wells/samplechemisorbed @ 230oC
C+ C- MCP/CuO DCBz/CuO MCBz/CuO Bz/CuO CT/CuO
LSU Chemistry Department 6/14/05 22
Radical/Particle SystemsSuppress P450 in the Lung
vehicle Cat./CuO DBBz/CuO DCBz/CuO
LSU Chemistry Department 6/14/05 23
Radical/Particle SystemsIncrease Free Radical Damage
LSU Chemistry Department 6/14/05 24
Myocardial ONNO .- is Evidence of Increased Oxidative Stress to Heart Tissue
LSU Chemistry Department 6/14/05 25
Increase in ROS in Heart Tissue by DHE Staining
Control Catechol/CuO
LSU Chemistry Department 6/14/05 26
Stabilization Mechanisms
OH
OH
Cu) O
OH
OH
O
CuOO O
OH
H
Physisorption
- H2O
Chemisorption
OH
Cu(II)
O
O
O
e- transfer
RadicalFormation
OH
O.
OH
O
Cu(I)
O O
Cu(I)
O O
.
Mesomerization
LSU Chemistry Department 6/14/05 27
Only Chemisorbed Chlorophenol Increases Lipid Peroxidation
LSU Chemistry Department 6/14/05 28
X
MetalO2
O
Men
O O
O
Men-1
O O
O
Me
ClPCDD/F
.
.
O.
O
HC Soot
O.2
-
ROS
CO
.OHOxidative
Stress
`
DNA damage
Lung disease
Heart disease
Liver disease
HO
HO
O
O
O
O
O2H2O2
O2
O2
NADPH or Ascorbate
NADP+ or Dehydroascorbate
Fe3+ Fe2+
OH
cellular damage
O
HOH2O H3O+
pH≥7.2
Airborne FineParticles
DNA Damage
Lung Disease
Heart Disease
Liver Disease
LSU Chemistry Department 6/14/05 29
Julien AdunkpeJulien Adunkpe Steven AldermanSteven Alderman RobinRobin McCarleyMcCarley Bill PryorBill Pryor Hongyi Hongyi WuWu
WayneWayne BackesBackes Randy HallRandy Hall Cheri McFerrinCheri McFerrin Hieu Hieu TruongTruong Mikhail Bryukov
Steph Steph CormierCormier Lavri Lavri KhachatryanKhachatryan SofiaSofia MaskoMasko Kurt VarnerKurt Varner Shadrack Ndyaie
Catherine EvansCatherine Evans Slawo LomnickiSlawo Lomnicki ErwinErwin PoliakoffPoliakoff JudyJudy WornatWornat
Rafael CuetoAndy DeutschGuis Squadrito
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