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SYNTHESIS AND APPLICATION OF BIOCOMPATIBLE DENDRONIZED POLYMERS FOR ANTIOXIDANT DISEASE PREVENTION
By: James Robinson
Central Michigan University
12/4/14
OUTLINE: Cellular Damage, Disease, Free Radicals
Generation based Dendrimers
Advantages and Disadvantages
From Dendron to Dendrimer
Antioxidant Testing
Future Expectations
CELLULAR DAMAGE AND DISEASE
Cellular Damage: UV Radiation Stress Metabolism Food Additives Smoking
Diseases: Cancer Diabetes Heart Disease Alzheimer’s Disease Aging Accelerant
FREE RADICALS AND THEIR PRODUCTION
Free Radical Species are often the cause…
Review on Free Radicals? Everyday species that are oxidized…
O2- (superoxide), (hydroxyl radical)
From stress, pollution, food, activities, AND oxygen…
Characteristics: Missing electrons Reactive Steals from healthy cells
HOW ARE THEY NEUTRALIZED?? Donation
Resonance
Antioxidants/Flavonoids
Apigenin
O
OH
HR
OH
O
+ R H
OH
O
OH
O
O
O
HR O
O
+ R H
DENDRIMERS WITH INCREASED ANTIOXIDANT ACTIVITY
D-Mannitol
D-Glucopyranoside
pentaerythritol
Nanah, Cyprien N. "Synthesis and Characterization of Various Antioxidant Dendrimers." Cmich.edu. N.p., 2012. Web. 2014.
WILL THESE MACROMOLECULES DO THE TRICK?
Increased Antioxidant Activity
Metal Chelation
“Living” Synthesis
Non-Toxic Ether Linkage
Possible Pro-oxidant Activity
Single Functionalized
Steric Hindrance
Increasingly Difficult to Purify
Advantages Disadvantages
CHALLENGES AHEAD…
Increased Functionality
Limitless Applications
Receptor Targeting
Less Hindrance
More Branching Opportunity
Increased Stability
Easier Purification
Higher Yield of Target
Less Amounts of Impurity
TWO DENDRONS TO A DENDRIMER…
*
*
*
*
ClO
OHNaN3
N3O
OHp-TOS
N3O
OTS
ClO
OOH NaN3 N3
OO
OH 1) TPP
2) H2OH2N
OO
OH
Boc2O
NH
OO
OHBocp-TOS
NH
OO
OTSBoc
O
HN
O
O
O
OTS
ON
O
O
O+
NH2
HO
OHOH +
NH
OO
BocHN
OH
OH
OH
NH
OO
OTSBocNH
OO
BocHN
O
O
O
O
O
O
N3
N3
N3
NH
OO
BocHN
O
O
O
O
O
O
N
N
N
NN
N
N
N
COOEt
COOEt
COOEtEtOOC
EtOOCCOOEt
NH
OO
BocHN
O
O
O
O
O
O
N
N
N
NN
N
N
N
COOH
COOH
COOHHOOC
HOOCCOOH
…AND BACK TO THE DENDRIMER…
“Living” Synthesis all over.
Possible “click chemistry” linkage.
Customizable pieces to a puzzle.
HNO
ONH O
OO
O
O
O
N
N
N
N N
N
N
N
COOH
HOOC
COOHHOOC
COOH
COOH
OO
NH
OO
O
O
O
O
N
N
N
NN
N
N
N
OO
O
O
O
O
OHHO
HOHO HO
HO
OHHO
HO
HOHO
OH
HOHO
OH
OH
HOHO
OH
OH
OHOHHO
OH
GOODBYE DISADVANTAGES! Multiple Functionalities on surface
Antioxidant Activity acid, phenolic, conjugated, ketone
Biocompatibility/Solubility Carbohydrate, amine, alcohol
Less Hindrance No Linker, Short Linker, Long Linker
Less Pro-oxidant effect Ether linkage Amine linkage Ester linkage
LASTLY, PURIFICATION...WITH GPC Dendron branched polymers!
ATRP
NMP
ROMP
NH
OOO
O
O
O
R
R
R
Cl
O
EtOn
NH
OOO
O
O
O
R
R
R
OO
O
nN
NH
OOO
O
O
O
R
R
R
Ru
n
TESTING OF ANTIOXIDANT STRENGTH
Oxygen Radical Absorbance Capacity
Test tube analysis Potential antioxidant levels Measures:
Free radical scavenging Oxygen inhibition
Various Laboratory Tests Levels of antioxidant
activity Extent of DNA and cellular
protection Measures:
LDL oxidation DNA oxidation Pro-oxidant effects Cell viability
O.R.A.C. Biochemical Tests
"Is the Antioxidant Era Over? - Nutrition Unplugged." Nutrition Unplugged. N.p., 25 May 2012. Web. 04 Dec. 2014.
FUTURE EXPECTATIONS?
Decreasing pro-oxidant activity with ion presence
Increasing Solubility with increasing free radical scavenging
Different techniques equals easier purification
Less hindrance equals more generations
IN CONCLUSION…
Many everyday causes of free radicals…
Long term cell damage leads to disease…
Natural antioxidant neutralization…
Customize potent antioxidants…
Antioxidant testing with improvement…
ACKNOWLEDGEMENTS
Dr. Lee Dr. Du
