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Britton Chance: His Life, Times, and Legacy June 3-4, 2011 University of Pennsylvania

Britton Chance: His Life, Times, and Legacy June 3-4, 2011 University of Pennsylvania. First With Creativity from masers and lasers to tunneling and P680, superoxide and beyond Robert A. Floyd Oklahoma Medical Research Foundation. BC’s Early papers – A Coalescing Interest.

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Britton Chance: His Life, Times, and Legacy June 3-4, 2011 University of Pennsylvania

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  1. Britton Chance: His Life, Times, and Legacy June 3-4, 2011 University of Pennsylvania First With Creativity from masers and lasers to tunneling and P680, superoxide and beyond Robert A. Floyd Oklahoma Medical Research Foundation

  2. BC’s Early papers – A Coalescing Interest Stable Spectrophotometry of Small Density Changes Chance, B – Rev SciInstrum 1947 18(9) 601-9 The Enzyme-Substrate Compounds of Catalase and Peroxides Chance, B – Nature 1948 161 (4102) 914-7 Effects of Oxygen upon Light Absorption by Green Algae Chance, B and Strekler, B – Nature 1957 180 (4589) 749-50 Cytochrome Reactions in Chromatuim Olson, JM and Chance, B – BBA 1958 28(1) 227-8

  3. BC’s Early papers – A Coalescing Interest Creative Spectroscopist Inquisitive View into Living Systems - All Dynamic Chromophores of Living Systems were of Interest - Seminal Observations were made in several important areas - Catalyzed more research at JF and in many other laboratories Hydrogen Peroxide Driven Reactions Involving Heme Proteins Photosynthetic Systems – Light Driven Reactions Oxygen Driven Dark Reactions/Mitochondrial Reactions

  4. Important Observations in Oxygen Biology 1968-1972 SOD Discovered McCord/Fridovich O2 Mw Boveris/Loschen/Chance Mitochondrial Mechanisms H2O2 Kasha/Kahn Bimol-mediated formation of photons 1O2 Floyd/DeVault/Chance + Primary photosystem II Reactions Temperature Independent at 220-80°K P680 cytb559

  5. Experimental Set Up Analyzing light beam Grating Sample Ruby Laser High pressure (4 ATM) hydrogen Grating Green laser light Green laser Red laser light 690nm Optical Cell PM Q-switched with spinning prism First Antistokes line ~540nm 680 nm t1/2 =4.5 msec CL CL Laser e P680 + hν cytb559 CL Temperature independent CL 220°K 80°K Floyd, Chance and DeVault; BBA 226;103 (1971)

  6. - 0.6 - 0.4 - 0.2 0.0 Standard electrode potential, V + 0.2 + 0.4 + 0.6 + 0.8 + 1.0 Green Plant Photosynthesis* P430 Ferredoxin Reductase NADPH Shunt pathway of cyclic electron flow e- e- NADPH+ Plastoquinone Z e- Pi+ ADP ATP e- Cyt b563 Cyt f hv Plastocyanin P700 Photosytem I e- ½O2 H2O hv P680 Photosytem II 2H+ • Adapted from A. Lehninger • Principles of Biochemistry

  7. Reactive Oxygen species (ROS) in Biology and Medicine -Major Area in Biomedical Research -Evolved from Damaging Species to Sophisticated Signaling System Alpha and gamma–tochopherols in Diseases A. Azzi Molecular Mechanisms O2 A. Boveris Translational Research Effort H2O2 H2O2 Mw Mw ROS in Stroke Oxidative Stress Anti-stroke Drugs H. Sies Nitrones/NXY-059 ROS in Cancer 8-OHdG 3O2 Anticancer Drugs Specific Traps for ROS Nitrones /OKN-007 Nitrones/salicylate + P680 cytb559 hv 1O2 MB RNA Virus Inactivation HIV, WNV, DENV Inactivated virus antigen Novel vaccines

  8. N H CH3 CH3 N S N - + C l CH3 CH3 Methylene Blue plus Light Inactivates RNA Viruses MB = Methylene Blue 1MB 3MB RNA Viruses HIV ~ 0.028* West Nile Virus - Hepatitis C Virus - 3O2 EC50(μM) light MB 1O2 Singlet Oxygen Potently produces 8-OHdG and 8-OHG 8-hydroxy-2’deoxyguanosine in DNA 8-hydroxy-guanosine in RNA *Table 4 U.S. Patent 6,346,529

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