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Group Research Interests - an overview

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Detect by voltammetry, LC-MS/MS. Example 1. Toxicity Screening ... Arrays: Which Liver Cytochrome P450s -generate toxic Benzo[a]pyrene Metabolites ... – PowerPoint PPT presentation

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Title: Group Research Interests - an overview


1
Group Research Interests - an overview
James F. Rusling Professor of Chemistry and
Pharmacology University of Connecticut and
University Health Center
2
Example 1. Toxicity Screening
Lipophilic Molecule
Cyt P450, O2
Enzyme-activated molecule
DNA
Damaged DNA
Detect by voltammetry, LC-MS/MS
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Collaboration with Prof. John Schenkman, Pharmacol
ogy, Uconn Health Center Funding from NIH, NIEHS
6
Screening Chemical Toxicity
Enzyme reaction - Incubate Reactant
H2O2--gtmetabolite
Analysis by catalytic SWV or electrochemiluminesc
ence
RuL2 RuL3 e- RuL3 DNA-G --gt RuL2
DNA-G
7
Enzyme/DNA films
Peak increase measures damage of DNA by
enzyme- generated metabolite
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Nucleobase adducts
9
Comparison of toxicity sensors with LC-MS For DNA
damage by methylmethane sulfonate
10
Alternative way to detect DNA damage with light
11
Arrays Which Liver Cytochrome P450s -generate
toxic Benzoapyrene Metabolites
12
Arrays detect in-vitro DNA damage from
metabolites of different enzymes with DNA/enzyme
films
Rel. turnover rate, 1/min (nmol Enzyme)
Drug development applications
13
Sensors for oxidative stress via oxidized DNA
Os-PVP
PSS
Pyrolytic Graphite
Ru-PVP
ECL detection in films Lynn Dennany, Robert J.
Forster, Blanaid White, Malcolm Smyth and James
F. Rusling, J. Am. Chem. Soc., 2004, 126,
8835-8841.
14
Single-Walled Carbon Nanotube Forests
Antigen-Antibody Sensing
SPAN or Nafion
Chattopadhyay, Galeska, Papadimitrakopoulos, J.
Am. Chem. Soc. 2001, 123, 9451.
End COOH groups allow chemical attachment to
proteins (antibodies)
15
AFM of SWNT forest with and without antibody
attached Collaboration with F. Papadimitrakopoulos
(ARO funded)
SWNT antibody (EDC coupling)
SWNT
16
Sandwich Assay for Human Serum Albumin
Ab2
HPR
SWNT forest
Apply E measure I
17
Detection of Human Serum albumin in 10 mL drops
on SWNT forest immunosensor
LOD 10 pmol/mL
18
Styrene Epoxidation Catalyzed by
Myoglobin-Polyion Films in Microemulsions (NSF
funded)
Stable in microemulsions
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  • Catalytic efficiency controlled by microemulsion
    composition

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Additional Current Projects Green chiral
synthesis using enzyme films in microemulsions,
nanoparticle catalysts (NSF) Redox chemistry of
complex photosynthetic proteins in membrane films
(with H. Frank, USDA funded) detection of Lyme
disease vectors (proteins) in tick saliva (with
Uconn Health Center) enzyme activity for
generating toxic metabolites (with Uconn Health
Center) EC-Laser fluorescent detection of DNA
damage arrays for anticancer biomarkers (NIH)
molecular dynamics of film construction
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