quantum chemical calculations of electron transfer from a model ascorbic acid free radical to...
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QUANTUM CHEMICAL CALCULATIONS OF ELECTRON TRANSFER FROM A MODEL ASCORBIC ACID
FREE RADICAL TO KETOALDEHYDES
Colin Thomson
Laboratory of the National Foundation for Cancer Research
Department of Chemistry University of St. Andrews
St. Andrews KYI6 9ST, Scotland
ABSTRACT
Ab-initio SCF calculations have been performed on
the anion radical derived from ~-hydroxytetronic
acid as a model for the ascorbic anion radical,
and its interaction with glyoxal. The results
show that the anion radical can act as an effec-
tive electron donor to glyoxal, and provide an
explanation for the enhancement of charge trans-
fer in amine/dicarbonyl systems by ascorbate.
It has been suggested by A. Szent-Gyorgyi [1] that
carbonyl compounds, and especially ketoaldehydes
(RCOCHO) such as methylglyoxal (MG), may act as
electron acceptors from protein molecules, de-
saturating the filled energy bands of the protein,
and rendering them conducting [2]
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The extensive experimental and theoretical work
on this subject has recently been reviewed at
a Ciba Symposium [3] . The electrical measurements
in particular [4] show that many different pro-
teins interact with MG to give highly conducting
coloured proteins. The importance of electronic
effects in these systems thus is now firmly
established.
In order to understand the interaction involved
in these charge transfer processes in more detail,
the model system methylamine/methylglyoxal has
been studied [5]. The initial reaction results
in the formation of a Schiff base in water, but in
acetone a purple solid is formed. It has been
shown that this is a polymeric species [6],
but it gives a strong ESR signal with rich
hyperfine structure, and this is believed to
be due to the purple charge transfer complex [7].
The important part played by ascorbic acid or one
of its metabolites in the charge transfer proces-
ses was suggested independently by Szent-Gyorgyi
and the author, and in support of this suggestion
was the observation that in the presence of as ~
corbate, the above reaction between methylamine
and MG is enhanced: the ESR signal becoming much
stronger [8].
In a previous paper [9], calculations were reported
on neutral ascorbic acid and the model Compound
a-hydroxy-tetronic acid, (Fig. i), together with
4O
H H
"° ' , -c / !i o
H o./C\\ / C I! 0
Figure i - ~-hydroxytetronic acid
the cation radicals derived from these molecules
by loss of an electron. ~-Hydroxy-tetronic acid
is a suitable model for ascorbic acid, since in
earlier work D0], it has been shown that the
highest occupied molecular orbitals, and the
electronic charge distribution are virtually
identical in the two molecules, which differ only
in the side chain.
These calculations [9] showed that the cation
radicals could act as strong electron acceptors,
and the earlier calculations by Thomson and
Ball [i0] showed that the neutral molecule could
act either as a donor or an acceptor with respect
to glyoxal, depending on the relative geometrical
positions of the two molecules.
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In the most recent experimental work on thfs system
[8 ], the ESR spectrum of the ascorbate free radical
is observed ~50 msec after mixing the reactants
in a flow system. This radical then rapidly
disappears and a new ESR spectrum replaces the
ascorbate spectrum, but this latter signal fs much
more intense, and ~s the same as that observed
at lower intensity in the absence of ascorbate.
We have recently established theoretically that
the ascorbate radical observed in solution by
E.S.R. must be the anion radical [9]:
spin density calculations rule out any other
radical. It therefore seems likely that the
anion radical acts as a donor to the ketoaldehyde,
and to establish whether this can in fact happen,
we have carried~ut ab-initio SCF calculations
on the ascorbate anion radical/glyoxal system
using the supermolecule approach described pre-
viously [10]. We have used the minimal STO-3G
basis set and only investigated a limited number
of stacked conformations of the system, since our
earlier results show this configuration to be the
most favourable for charge transfer (Fig. 2).
The results of the calculations at a separation O
of 2.8 A for the configuratfon with maximum
charge transfer show clearly that the anion
radical can act as a donor to glyoxal, the ex-
tent of the transfer of charge amounting
to ~0.03e. This is approximately a factor of four
greater than found for the neutral molecule,
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H H
/ -0\ C \ H. ..0....
o >c=o / _o-C-C-.o.
C II 0
Q. ~C-H
H-C~ °
Figure 2 - ~-hydroxytetronate anion radical
and the supermolecule ~-hydroxyte-
tronate radical/glyoxal in the stacked
conformation.
In conclusion, therefore, it seems likely that the
enhancement of charge transfer found in the pre-
sence of ascorbic acid is due to the initial
production of the ascorbate anion radical, which
can then act as an electron donor to the keto-
aldehyde. It seems more likely that this is the
process involved in these reactions, rather than
electron transfer to the cation radical, for
the latter is incompatible with the E.S.R.
evidence.
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ACKNOWLEDGEMENT
We thank the National Foundation for Cancer Re-
search, Inc., for financial support, and
P. Gascoyne for useful discussions of his
unpublished work.
REFERENCES
I. Szent-Gyo'rgyi, Ao (1976) Int. J. Quantum Chem.
QBS3, 45-50; Szent-Gy~rgyi, A. (1977) Int.
J. Quantum Chem. QBS4, 179-84.
2. Szent-Gyorgi, A. (1976) Electronic Biology
and Cancer, Dekker, New York.
3. Ciba Symposium New Series (1979) No. 67,
Excerpta Medica, Amsterdam.
4. Bone, S., Lewis, T. J., Pethig, R.,
~nd Szent-Gyorgyi, A. (1978). Proc.
Natl. Acad. Sci. U.S.A. 75, 315-318.
5. Szent-Gyorgyi, A. (1978) 'The Living
State" and Cancer', Dekker, New York.
6. Pohl, H., and Szent-Gyorgyi, A., un-
published results.
7. Szent-Gyorgyi, A. Ref. 3, p. ii.
8. Gascoyne, P., unpublished results.
9. Otto, P., Ladik, J., and Szent-Gyorgyi, A.
(1979) Proc. Natl. Acad. Sci. U.S.A.
(accepted) .
i0. Thomson, C. and Ball, J. R., Ciba Symposium
New series (1979) No. 67, 143-160.
ii. Thomson, C., (1980) Theor. Chim. Acta.,
(submitted) .
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