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,

42

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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