CHAPTER 8: OXIDATIVE-PHOSPHORYLATION
A: THE CHEMISTRY OF DIOXYGEN
BIOCHEMISTRY - DR. JAKUBOWSKI
04/14/16
Learning Goals/Objectives for Chapter 8A: After class and
this reading, students will be able to
- explain why oxidation reactions with ground state dioxygen
have a high enough activation energy to make the reactions,
although thermodynamically favored, kinetically slow
- explain, using molecular orbital diagrams the difference
between triplet and singlet dioxygen
- using molecular orbital diagrams and Lewis structures,
describe the chemical properties of the reduction products of
dioxygen (superoxide, peroxide, and water)
- explain the ways that biological systems use to enhance
dioxygen activity and reduce the effects of reactive oxygen
species (ROS) such as superoxide and peroxide
- write chemical reactions and mechanisms when appropriate
for some reactions of triplet and singlet dioxygen, superoxide,
peroxide and the hydroxy free radical
- describe typical reaction of ROS with lipids, proteins, and
nucleic acids and data to support the involvement of ROS in
complex diseases and aging.
- Briefly contrast the production and biological activities of
ROS and reactive nitrogen intermediates (RNIs)
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A3. The Reactions of Dioxygen and its Reduction Products
1. Triplet O2 - Ground State:
Figure:
Triplet O2 - Ground State
- Metals ions - Metal ions are radicals
themselves, so can react with dioxygen. Ex:
Fe2+ + O2 <--> [ Fe2+--
O2 <--> Fe3+-- O2-.] <--> Fe3+ + O2-. (superoxide)
- Autoxidation of organic molecules to
produce peroxides. In this free radical reaction, several reactions
occur, including
RH ---> R. (Initiation)
R. + O2 ---> ROO.
(Propagation)
ROO. + RH ---> R. + ROOH (Propagation)
R. + R. --->
R--R (Termination)
ROO. + ROO. ---> ROOR + O2 (Termination)
ROO. +
R. ---> ROOR (Termination)
The initiation step above occurs
mostly at C atoms which can produce the most stable free radicals (allylic,
benzylic position, and 3o > 2o >> 10 carbons). Hence unsaturated fatty
acids are extra reactive at the methylene C that separate the double
bonds.
Figure:
unsaturated fatty acids are extra reactive at the methylene C that separate
the double bonds
2. Single O2 - Excited State.
Figure:
Single O2 - Excited State
It can be made from triplet oxygen by photoexcitation.
Alternatively, it can be made from triplet oxygen through collision with an
excited molecule which relaxes to the ground state after a radiationless
transfer of energy to triplet oxygen to form reactive singlet oxygen. (This
later process accounts for photobleaching of colored clothes when the
conjugated dye molecules absorb UV and Vis light, relax by transferring
energy to triplet oxygen to form singlet oxygen, which then chemically
reacts with the conjugated double bonds in the dye. )
- Alkenes react with oxygen to form hydroperoxides, potentially
through a epoxide intermediate
- Dienes reacts with oxygen in a Diels-Alder like reaction to form
endoperoxides
3. Superoxide
Figure:
Superoxide
- Dismuation: O2-. + O2-.
---> H2O2 + O2
- Acid/Base: HO2. ----> O2-. + H+
(pKa = 4.8)
- With metal ions: Fe3+ (as in heme) + O2-.
---> O 2 + Fe2+
4. Peroxide
Figure:
Peroxide
In contrast to dioxygen which contains multiple
bonds between the O atoms, peroxide has only one bond. In fact, it is
quite weak and requires only 38 kcal/mol to break it. Remember, bonds can be
broken in a heterolytic way (both electrons in a bond go to one of the
atoms, or in a homolytic fashion, in which the one electron goes to each
atom.
- Acid/Base: H2O2 ---> HO2- ---> O22- (pKa1
= 11.8; pKa2 > 14)
- Reaction with Fe2+ - The Fenton Reaction:
(similar to reaction of triplet O2 with Fe2+ above)
Fe2+ + OOH- <-->
Fe2+-- OOH <--> Fe2+-- O + OH- <--> Fe3+-- O . <--> Fe3+ + OH. (last
step a proton is added). In this reaction, a homolytic cleavage of the
O--O bond occurs generating OH- and the hydroxy free radical, OH., which
will react with any molecule it encounters.
- thermal or photochemical homolytic cleavage of peroxide. This forms
alkoxide free radicals which reacts like the hydroxy free radical.
- Reactions with alkyl groups in the
presence of metal ions such as Cu, Co, or Mn:
RH + R'OOH ----> ROOR'
5. Hydroxy free radical:
Figure:
Hydroxy free radical
As mentioned above this species is extremely reactive. It will react with
any molecule it encounters and does so immediately. It can abstract a H atom
leaving another free radical. For example, the hydroxy free radical
could extract a hydrogen atom from a polyunsaturated fatty acid to from a
carbon-centered radical. A particularly nasty reaction is the
insertion of the hydroxy radical into bases in DNA, as shown in the diagram.
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