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Group Research Interests - an overview

Group Research Interests - an overview. James F. Rusling Professor of Chemistry and Pharmacology University of Connecticut and University Health Center. Example 1. Toxicity Screening. Lipophilic Molecule. Cyt P450, O 2. Enzyme-activated molecule. + DNA. Damaged DNA.

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Group Research Interests - an overview

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  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

  3. Collaboration with Prof. John Schenkman, Pharmacology, Uconn Health Center Funding from NIH, NIEHS

  4. Screening Chemical Toxicity Enzyme reaction - Incubate: Reactant + H2O2-->metabolite Analysis by catalytic SWV or electrochemiluminescence RuL2+ = RuL3+ + e- RuL3+ + DNA-G --> RuL2+ + DNA-G•

  5. Enzyme/DNA films Peak increase measures damage of DNA by enzyme- generated metabolite

  6. Nucleobase adducts

  7. Comparison of toxicity sensors with LC-MS For DNA damage by methylmethane sulfonate

  8. Alternative way to detect DNA damage with light

  9. Arrays: Which Liver Cytochrome P450s -generate toxic Benzo[a]pyrene Metabolites

  10. 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

  11. 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.

  12. 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)

  13. (b) (a) AFM of SWNT forest with and without antibody attached Collaboration with F. Papadimitrakopoulos (ARO funded) SWNT + antibody (EDC coupling) SWNT

  14. H2O2 HRP HRP HRP HRP HRP HRP Ag Ag Ab1 Ab1 Sandwich Assay for Human Serum Albumin Ab2 HPR SWNT forest Apply E measure I

  15. Detection of Human Serum albumin in 10 mL drops on SWNT forest immunosensor LOD ~ 10 pmol/mL

  16. Styrene Epoxidation Catalyzed by Myoglobin-Polyion Films in Microemulsions (NSF funded) Stable in microemulsions

  17. Catalytic efficiency controlled by microemulsion composition

  18. 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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