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
Stable Spectrophotometry of Small Density Changes
Chance, B – Rev Sci Instrum 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
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
Important Observations in Oxygen Biology
1968-1972
McCord/Fridovich
Boveris/Loschen/Chance
Kasha/Kahn
Floyd/DeVault/Chance
O2
Mw
SOD Discovered
H2O2
1O
2
cytb559 P+680
Mitochondrial Mechanisms
Bimol-mediated formation of photons
Primary photosystem II Reactions
Temperature Independent at 220-80°K
Experimental Set Up
Analyzing
light beam
Ruby Laser
Q-switched with
spinning prism
Sample
High pressure
(4 ATM)
hydrogen
Red
laser light
690nm
Optical Cell
Grating
Grating
Green
laser
light
Green
laser
First Antistokes
line ~540nm
680 nm
t1/2 =4.5 msec
CL
CL
+
hν
P680
e
Laser
cytb559
CL
CL
Temperature independent
220°K
80°K
Floyd, Chance and DeVault; BBA 226;103 (1971)
Green Plant Photosynthesis*
Standard electrode potential, V
- 0.4
P430
Ferredoxin
- 0.6
NADPH
Reductase
e-
Shunt pathway
of cyclic electron flow
e-
- 0.2
NADPH+
Plastoquinone
Pi+
ADP
ATP
+ 0.2
e-
Cyt b563
Cyt f
+ 0.4
hv
P700
+ 0.6
Z
e-
0.0
Plastocyanin
e-
Photosytem
I
+ 0.8
½O2
hv
+ 1.0
P680
Photosytem
II
H2O
2H+
•Adapted from A. Lehninger
Principles of Biochemistry
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
Mw
H2O2
A. Boveris
ROS in Stroke
Oxidative Stress
H. Sies
Anti-stroke Drugs
Nitrones/NXY-059
O2
Mw
ROS in Cancer
8-OHdG
H2O2
3O
2
cytb559 P+680
Translational
Research
Effort
Anticancer Drugs
Nitrones /OKN-007
Specific Traps for ROS
Nitrones/salicylate
MB
hv
1O
2
RNA Virus Inactivation
HIV, WNV, DENV
Inactivated virus
antigen
Novel vaccines
Manuscript s Submit t ed
f or Considerat ion
1300
Manuscripts Submitted
1200
1100
1000
900
800
700
600
500
400
300
200
Submission Predictions:
2010 - 1,170 manuscripts
Average of approximately 98 papers/month
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
Year of Publication
1991 - 211 manuscripts
1992 - 257 manuscripts
1993 - 316 manuscripts
1994 - 351 manuscripts
1995 - 450 manuscripts
1996 - 479 manuscripts
1997 - 532 manuscripts
1998 - 654 manuscripts
1999 - 705 manuscripts
2000 - 821 manuscripts
2001 - 843 manuscripts
2002 - 895 manuscripts
2003 - 825 manuscripts
2004 - 999 manuscripts
2005 - 1,077 manuscripts
2006 - 1,120 manuscripts
2007 - 1,109 manuscripts
2008 - 1,167 manuscripts
2009 - 1,113 manuscripts
Methylene Blue plus Light Inactivates RNA Viruses
N
MB =
CH3
N
Methylene Blue
CH3
1MB
H
S
+ C l-
CH3
N
CH3
3MB
3O
2
light
MB
1O
2
Singlet Oxygen
RNA Viruses
HIV
EC50(μM)
~ 0.028*
West Nile Virus
-
Hepatitis C Virus
-
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