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The organic and biological chemistry of molecular
oxygen is of extraordinary interest. Oxygen plays an important
role in aging, damage to materials in the environment, cellular
pathology (for example, the damage following stroke or heart attack)
and many other areas. The details of the chemical reactions underlying
these processes are poorly understood. The Foote group uses preparative,
physical-organic, and bioorganic methods to study the chemistry
of molecular oxygen in photochemical and biological processes.
Reactive intermediates include singlet oxygen (1O2, a metastable
excited state of molecular oxygen), superoxide ion, and other
oxygen species.1,2
Singlet oxygen can be generated by many chemical
and photochemical processes. A common way is by photochemical
excitation of a sensitizer (Sens) to an electronically excited
state (*Sens) followed by energy transfer from the excited sensitizer
to oxygen.
Singlet oxygen is very toxic to organisms because
it reacts with important biological molecules such as unsaturated
lipids, oxidizable amino acids, and nucleic acids, particularly
guanosine derivatives. The resulting reactions cause destruction
of membranes, enzyme inactivation, and mutations, all of which
can lead to cell death. We are carrying out extensive studies
of the reactions with biological target molecules and have characterized
many of the primary products of these reactions. For example,
photooxidaton of guanosine derivatives gives endoperoxides that
are stable only at low temperatures. This reaction is responsible
for genetic damage caused by sensitizing molecules, light, and
oxygen.3
Singlet oxygen also reacts with many organic compounds to give adducts which have utility in synthesis or are biological intermediates. Some examples are shown below.4-7
Extensive mechanistic and preparative studies of the reactions of singlet oxygen are under way. For example, the reactions of indoles have been shown to depend critically on their structures. Some remarkable reactions of potential synthetic utility have been found; examples are shown below.8,9
Singlet oxygen can be conveniently observed
by measuring its weak infrared emission using an ultrasensitive
germanium diode detection system. If the sensitizer is excited
by a short laser pulse, the emission can be followed as a function
of time using a sophisticated system for computerized data acquisition
and analysis. This technique allows a simple and accurate method
of measuring the decay and reaction rates of this species as well
as the efficiency of its production.10
Reactive intermediates in these reactions are
monitored by techniques that include laser flash photolysis, low
temperature NMR spectroscopy, kinetic methods, and isolation.
Some species characterized by such techniques in the last few
years are shown below.11-17
A very important medical application of photosensitized oxidations
is in photochemical killing of organisms. Oxygen-dependent photosensitized
toxic effects are extremely common in nature, and are used, for
example, by fungi to gain entry to cells by damaging protective
membranes, or by plants to kill insects (or injure mammals) which
feed on them. A particularly exciting application of this type
of chemistry is the recent use of sensitizer, light, and oxygen
to kill tumor cells selectively in humans.20 Studies of the mechanism
of action of such sensitizers and attempts to prepare more effective
ones are in progress.
Recently, we showed that the fascinating all-carbon molecules
("buckyballs") C60 and C70 have are powerful photosensitizers
for the production of singlet oxygen, and their photophysical
properties were characterized for the first time.21,22 Photochemical
electron-transfer to and from these interesting molecules is possible.23,24
We also prepared some of the first stable characterizable derivatives,
such as the dioxolane shown below.25
The most efficient method so far of functionalizing C60 is
photochemical [2 + 2] addition of the ynamine shown below to give
the adduct cyclobutane enamine. The buckyball residue photosensitizes
the oxidation of the enamine, and the difunctional adduct shown
below is formed in 92% overall yield.26
These are a few representative examples of ongoing work in this group. In summary, techniques from preparative and physical-organic chemistry and biochemistry are used as necessary to establish the role of key reactions of singlet oxygen or other species in chemical systems that are important to organic, biological, and medical science.
Representative Recent Publications
1. Foote CS; Valentine JS; Greenberg A; Liebman J F (Eds). Active Oxygen in Chemistry. London, Chapman and Hall, 1995, vol 2.
2. Valentine JS; Foote CS; Greenberg A; Liebman JF (Eds). Active Oxygen in Biochemistry. London, Chapman and Hall, 1995, vol 3, pp 1.
3. Sheu C; Foote CS. "Endoperoxide Formation in a Guanosine Derivative." J. Am. Chem. Soc. 1993, 115, 10446.
4. Kwon BM; Foote CS; Khan SI. "Photooxygenation of Ascorbic Acid Derivatives and Model Compounds." J. Am. Chem. Soc. 1989, 111, 1854.
5. Kwon BM; Kanner RC; Foote CS. "Reaction of Singlet Oxygen with 2-Cyclopenten-1-Ones." Tetrahedron Lett. 1989, 30, 903.
6. Kwon BM; Foote CS; Khan SI. "Chemistry of Singlet Oxygen. 52. Reaction with trans-Stilbene." J. Org. Chem. 1989, 54, 3378.
7. Zhang X; Lin F; Foote CS. "Sensitized Photooxygenation
of 6-Heteroatom-Substituted Fulvenes: Primary Products and Their
Chemical
Transformations." J. Org. Chem. 1995, 60, 1333.
8. Zhang X; Foote CS; Khan SI. "Reactions of N-Acylated Indoles with Singlet Oxygen." J. Org. Chem. 1993, 58, 47.
9. Zhang X; Khan SI; Foote CS. "Sensitized Photooxygenations of 3-Vinylindole Derivatives." J. Org. Chem. 1993, 58, 7839.
10. Foote CS. "Dicyanoanthracene Sensitized Photo-oxygenation
of Olefins: Electron Transfer and Singlet Oxygen Mechanisms."
Tetrahedron 1985, 41,
2221.
11. O'Shea KE; Foote CS. "Chemistry of Singlet Oxygen. 51. Zwitterionic Intermediates from 2,4-Hexadienes." J. Am. Chem. Soc. 1988, 110, 7167.
12. Orfanopoulos M; Smonou I; Foote CS. "Intermediates
in the Ene Reactions of Singlet Oxygen and -Phenyl-1,2,4- triazoline-3,5-dione
with Olefins."
J. Am. Chem. Soc. 1990, 112, 3607.
13. Nahm K; Foote CS. "Trimethyl Phosphite Traps Intermediates in the Reaction of O2 and Diethyl Sulfide." J. Am. Chem. Soc. 1989, 111, 1909.
14. Stratakis M; Orfanopoulos M; Foote CS. "Nucleophilic Oxygen Transfer from a Perepoxide to Phosphites." Tetrahedron Lett. 1991, 32, 863.
15. Sheu C; Foote CS; Gu CL. "Photooxidation of 1,5-Dithiacyclooctane. A Novel C-S Bond Cleavage." J. Am. Chem. Soc. 1992, 114, 3015.
16. Sheu C; Foote CS. "Photosensitized Oxygenation of
a 7,8-Dihydro-8-oxoguanosine derivative. Formation of Dioxetane
and Hydroperoxide
Intermediates." J. Am. Chem. Soc. 1995, 117, 474.
17. Sheu C; Foote CS. "Reactivity toward Singlet Oxygen
of a 7,8-Dihydro-8-oxoguanosine ("8-Hydroxyguanosine")
Formed by Photooxidation of a
Guanosine Derivative." J. Am. Chem. Soc. 1995, 117, 6439.
18. Elemes Y; Foote CS. "Stepwise Mechanisms in the Ene
Reaction of a,B-Unsaturated Esters with N-Phenyl-1,2, 4-triazoline-3,5-dione
and Singlet
Oxygen. Intermolecular Primary and Secondary Hydrogen Isotope
Effects." J. Am. Chem. Soc. 1992, 114, 6044.
19. Poon THW; Park SH; Elemes Y; Foote CS. "Reaction of
N-Substituted 1,2,4-Triazoline-3,5-diones and trans-Cyclooctene.
Direct Observation of an
Aziridinium Imide." J. Am. Chem. Soc. 1995, 117, 10468.
20. Foote CS. "'Mechanistic Characterization of Photosensitized
Reactions' In Photosensitisation." NATO ASI Series H: Cell
Biology; (Moreno G; Pottier
RH; Truscott TG: Eds), Heidelberg, Springer Verlag, 1988, pp 125.
21. Arbogast JW; Darmanyan AO; Foote CS; Rubin Y; Diederich
FN; Alvarez MM; Anz SJ; Whetten RL. "Photophysical Properties
of C60." J. Phys. Chem.
1991, 95, 11.
22. Arbogast JW; Foote CS. "Photophysical Properties of C70. J. Am. Chem. Soc. 1991, 113, 8886.
23. Arbogast JW; Foote CS; Kao M. "Electron Transfer to Triplet C60. J. Am. Chem. Soc. 1992, 114, 2277.
24. Nonell S; Arbogast JW; Foote CS. "Production of C60 Radical Cation by Photosensitized Electron Transfer." J. Phys. Chem. 1992, 96, 4169.
25. Elemes Y; Silverman SK; Sheu C; Kao M; Foote CS; Alvarez
MM; Whetten RL. "Reaction of C60 with dimethyldioxirane to
give an epoxide and a
1,3-dioxolane adduct." Angew. Chem. Int. Ed. Engl. 1992,
31, 351.
26. Zhang XZ; Fan A; Foote CS. "[2+2] Cycloaddition of Fullerene with Electron-Rich Alkenes and Alkynes." J. Org. Chem. 1996, 61, 5456.
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Email: Professor
Christopher S. Foote |
University of California, Los Angeles Department of Chemistry and Biochemistry 405 Hilgard Avenue P.O. Box 951569 Los Angeles, CA 90095-1569 |
updated 10/1/99
