Group Research Interests - an overview James F. Rusling Professor of Chemistry and Pharmacology University of Connecticut and University Health Center.

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Presentation transcript:

Group Research Interests - an overview James F. Rusling Professor of Chemistry and Pharmacology University of Connecticut and University Health Center

Lipophilic Molecule Cyt P450, O 2 Enzyme-activated molecule + DNA Damaged DNA Detect by voltammetry, LC-MS/MS Example 1. Toxicity Screening

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

Enzyme reaction - Incubate: Reactant + H 2 O 2 -->metabolite Analysis by catalytic SWV or electrochemiluminescence RuL 2+ = RuL 3+ + e- RuL 3+ + DNA-G --> RuL 2+ + DNA-G Screening Chemical Toxicity

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

Nucleobase adducts

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

Alternative way to detect DNA damage with light

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

Arrays detect in-vitro DNA damage from metabolites of different enzymes with DNA/enzyme films Mb0.9 P450cam3.0 P450 1A23.5 Rel. turnover rate, 1/min (nmol Enzyme) Drug development applications

Pyrolytic Graphite Os-PVP Ru-PVP PSS Sensors for oxidative stress via oxidized DNA ECL detection in films: Lynn Dennany, Robert J. Forster, Blanaid White, Malcolm Smyth and James F. Rusling, J. Am. Chem. Soc., 2004, 126,

Single-Walled Carbon Nanotube Forests: Antigen-Antibody Sensing SPAN or Nafion Chattopadhyay, Galeska, Papadimitrakopoulos, J. Am. Chem. Soc. 2001, 123, End COOH groups allow chemical attachment to proteins (antibodies)

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

Sandwich Assay for Human Serum Albumin H2O2H2O2 Ab1 Ag HRP Ab1 Ag HRPHRP HPR Ab 2 Apply E measure I SWNT forest

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

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

–Catalytic efficiency controlled by microemulsion composition

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