Reduction of maleate and fumarate by the CO2.- anion radical

Article abstract of DOI:10.1016/j.tetlet.2005.12.042

The radical anion CO₂^.- reacts with fumarate and maleate at pH 5.3 mainly via electron transfer. The final products are a mixture of (^-O₂CCH₂-)₂, trans-( ^-O₂CCH)₂ and products with higher molecular weight. At higher pHs, the yield of fumarate and succinate decreases. The results suggest that though the radical anions formed by the reduction of fumarate and maleate have different structures, the final products are probably the same.

Full text of DOI:10.1016/j.tetlet.2005.12.042

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1093–1096
.ꢀ
Reduction of maleate and fumarate by the CO2 anion radical
Osnat Schutza and Dan Meyersteina,b,
*
aChemistry Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel
bBiological Chemistry Department, College of Judea and Samaria, Ariel, Israel
Received 30 October 2005; revised 29 November 2005; accepted 7 December 2005
Available online 27 December 2005
.ꢀ
Abstract—The radical anion CO2 reacts with fumarate and maleate at pH 5.3 mainly via electron transfer. The final products are a
mixture of (ꢀO2CCH2–)2, trans-(ꢀO2CCH@)2 and products with higher molecular weight. At higher pHs, the yield of fumarate and
succinate decreases. The results suggest that though the radical anions formed by the reduction of fumarate and maleate have dif-
ferent structures, the final products are probably the same.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The reduction of maleate and fumarate in neutral and
slightly acidic aqueous solutions by NiIL+ and CoIL+
complexes, where L are tetraazamacrocyclic ligands1,2
has been studied in aqueous solutions containing
HCOꢀ2 . As a blank it was decided to determine the nat-
ure of the major final products when maleate and fuma-
The reduction of fumarate with eꢀaq was suggested to
form the radical anion III,3 which is transformed into
the radical anion IV.4
The pKa of the latter transformation is not clear, Neta3
observed the radical anion III at pH 6.9 whereas Hayon
and Simic suggested a pKa of 10.9 for this anion.5
.ꢀ
rate are reduced by CO2 . It should be noted that the
literature contains conflicting reports on the reaction
.ꢀ
of CO2 with these acids. Neta3 and Anderson et al.4
It should be noted that all the EPR spectra indicate that
the unpaired electron density in all these radical anions
is located mainly on the carbon atoms of the carboxylic
groups. It seemed therefore of interest to study the nat-
ure of the final products obtained when maleate and
have suggestedꢀ that the ꢀmajor product is the radical
anion CHðCO2 ÞCHðCO2 Þ2 whereas Hayon and Simic5
.
reported that at least at pH ꢁ 5, the major products are
the radical anions formed by an electron transfer pro-
cess. At higher pHs, the latter reactions were not
observed.
.ꢀ
fumarate react with eaꢀq and with the CO2 radical anion.
Maleic or fumaric acid with an initial concentration of
3 · 10ꢀ4 M was added to a solution of 0.1 M sodium
formate and 0.1 M phosphate buffer at different pH
values (5.3; 7.0; 8.0) with He or N2O saturation. The
samples were c irradiated using a 60Co c source in sealed
EPR eꢀxperiments6 suggest that the reduction of maleate
with eaq at pH > 7 yields the radical anion I, which is
transformed into the radical anion II6 with a pKa of
5–6.5
. -
.
2-
O
C
H
O
C
O
C
H
O
C
O
C
C
O H
O
C
C
O
H
H
H
H
I
II
*
Corresponding author. Tel.: +972 86472737; fax: +972 86472943; e-mail: danmeyer@bgu.ac.il
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.042

1094
O. Schutz, D. Meyerstein / Tetrahedron Letters 47 (2006) 1093–1096
. 3 -
O
O
C
CH
C
CH
O
O
III
-
O
-
H
CO2
.
C
H
C
OH
C
.
C
HO
H
C
C
-
-
O2C
H
O
IV
bulbs for 20–90 min (66–297 Gy). The results are sum-
marized in Table 1. Product analysis was performed as
described in Ref. 7.
trode). Thus, in neutral He saturated solutions contain-
ing formate, two strong reducing radicals are formed eaꢀq
(ꢁ45% of the radicals) and CO.2ꢀ (ꢁ55% of the radicals).
In N2O saturated solutions, [N2O] = 0.022 M, the eaꢀq
react via9
.ꢀ
CO2 radical ion production: When ionizing radiation is
absorbed in neutral dilute aqueous solutions, the forma-
tion of the primary radicals is summed up in the follow-
ing equation:8
Hþ
eꢀaq þ N2O ! OH þ N2 k ¼ 9:1 ꢂ 109 Mꢀ1 sꢀ1
.
Thus, in these solutions all the radicals are transformed
into the CO2 ion radical.
.ꢀ
c
.
H2O ! eꢀaq ð2:65Þ; OH ð2:65Þ; H ð0:60Þ;
.
H2O2 ð0:75Þ; H2 ð0:40Þ
The measured yields, and decrease in concentration or
formation of maleate and fumarate were measured.
The results are summarized in Table 1.
The G values are given in parentheses (G values are
defined as the number of molecules of each product
per 100 eV of radiation absorbed by the solution).8
When formate is present in the solution, the following
reactions take place:9
Succinate was observed as one of the products in all
samples. However, accurate yields could not be deter-
mined due to the low absorption coefficient in the UV
and some overlap with the fumarate peak due to similar
retention times. Other products with longer retention
times and thus probably with larger molecular weights
and/or negative charges, were observed.
HCO2 þ OH=H ! CO.2ꢀ þ H2O=H2
ꢀ
.
.
k.OH ¼ 2:9 ꢂ 109 Mꢀ1 sꢀ1
k.H ¼ 2:5 ꢂ 108 Mꢀ1 sꢀ1
.ꢀ
The CO2 radical anion is a very strong reducing agent
The results for the He saturated maleate solutions at
pH 5.3 indicate the following conclusions:
E0 = ꢀ1.9 V10 versus NHE (normal hydrogen elec-
(a) Fumarate is a major product of the reaction of radi-
Table 1. Yields of maleate or fumarate after c-irradiation
cals I or II. This is expected to occur via
2II ! trans-ꢀO2CCH@CHCOꢀ2
þ ꢀO2CCH2CH2CO2ꢀ þ 2Hþ
or via
Sample
pH Saturation Gaof maleate
Ga of fumarate
gas
Maleate
Maleate
Maleate
Fumarate 5.3 He
Fumarate 7.0 He
Fumarate 8.0 He
Maleate
Maleate
Maleate
Fumarate 5.3 N2O
Fumarate 7.0 N2O
Fumarate 8.0 N2O
5.3 He
7.0 He
8.0 He
G = ꢀ7.6 0.5 G = 2.7 0.1
G = ꢀ6.9 1.0 G = 1.4 0.1
G = ꢀ7.0 0.4 G = 1.2b
G = 0.05c
G = 0.3c
G = 0.7c
G = ꢀ4.7 0.5
G = ꢀ5.4 1.0
G = ꢀ7.6 0.6
2I ! trans-ꢀO2CCH@CHCOꢀ2
þ ꢀO2CCH2CH2COꢀ2
5.3 N2O
7.0 N2O
8.0 N2O
G = ꢀ8.9 0.6 G = 3.8 0.2
G = ꢀ7.7 0.8 G = 1.9 0.2
G = ꢀ7.2 0.8 G = 0.9 0.1
(b) As G(-maleate) = 7.6 and G(-fumarate + succi-
nate) = 5.4 clearly other, heavier, products with
G ꢁ 2.2 are formed. These might be due to the addi-
G = 0.03b
G = 0.3b
G = ꢀ3.4 0.4
G = ꢀ5.3 1.0
G = ꢀ6.9 0.4
.ꢀ
tion of CO2 to the double bond of maleate, which
G = 1.0 0.1
was observed as
a major product by EPR
spectroscopy.4
a G is defined as the number of molecules of each product per 100 eV of
radiation absorbed by the solution.8
b At 66 Gy, the yield decreases with increasing dose.
c At 148 Gy, the yield decreases with increasing dose.
(c) Thꢀe fact that G(-maleate) is somewhat larger than
Geaq þ G.OH þ G.H ¼ 5:9 in neutral solutions8 might
indicate that the reactions

O. Schutz, D. Meyerstein / Tetrahedron Letters 47 (2006) 1093–1096
1095
Hþ
.ꢀ
I=II þ HCOꢀ2 ! ꢀO2CCH2CH2CO2ꢀ þ CO2
tical with the yields of fumarate in the maleate system at
these pHs. This observation was unexpected as it sug-
gests that
occur. Analogous reactions were recently ob-
served.2,11 Alternatively, and/or, this increase in
yields might be due to .OH scavenging from spurs12
by formate.
(a) The yields of electron transfer in the reactions of
.ꢀ
CO2 with maleate and fumarate are similar. This
(d) The observation that fumarate is a major product
indicates that though the cyclic nature of intermedi-
ates I and II is maintained in their reactions, at least
in those of II, the unpaired electron is located pri-
marily on the –CH– groups and enables the forma-
tion of products which require rotation of the CH–
CH bond.
conclusion contradicts earlier suggestions based
on the UV absorptions of the radicals formed.5
(b) The chemical properties of the radical anions I/II
are similar to those of the radical anions III/IV.
Thus, it is tempting to suggest that though the radical
anions I/II and III/IV are clearly different, as the EPR
spectra point out, they decompose via
The somewhat larger yields in the N2O saturated solu-
tions is mainly attributed to the scavenging of eꢀaq from
spurs by N2O which is known to increase the radical
yields by ca. 0.7.9 It is of interest to note that UV studies
H2O
ꢀ
ꢀ
.
I=II or III=IV ! CHðCO2 ÞCH2CO2
ꢀ
ꢀ
.
and the radicals CHðCO2 ÞCHðCO2 Þ2 then decompose
.ꢀ
mainly via
indicate that ca. 65% of the reaction of CO2 with male-
ate results in electron transfer,5 which is in good agree-
ment with our results in the N2O saturated solutions at
pH 5.3.
ꢀ
ꢀ
ꢀ
.
2 CHðCO2 ÞCH2CO2 ! trans-ꢀO2CCH@CHCO2
þ ꢀO2CCH2CH2COꢀ2
and to some degree via
The decrease of G(-fumarate) with the increase in pH,
without a decrease in G(-maleate) is probably due to
an increase in the yield of CO2 addition to maleate
and a decrease in the yield of the electron transfer in this
reaction.
ꢀ
ꢀ
ꢀ
ꢀ
2 CHðCO2 ÞCH2CO2 ! ðꢀO2CCH2CHðCO2 Þ Þ2
.
.ꢀ
and via
ꢀ
ꢀ
ꢀ
.
CHðCO2 ÞCH2CO2 þ ꢀO2CCH@CHðCO2 Þ
ꢀ
ꢀ
ꢀ
ꢀ
.
! CHðCO2 ÞCHðCO2 ÞCHðCO2 ÞCH2CO2
-
-
.CH(CO2 )CH(CO2 )2
Thus, the results suggest that the mechanism of reaction
of the radical anions in the two systems are similar
though the structures of the initial radical anions formed
are different.
a
.-
-
CO2 + cis- -O2CCH=CHCO2
b
I + CO2
This suggestion is in accord with UV studies on the yield
of electron transfer in this reaction.5 Alternatively, it is
plausible that radical anion I tends to dimerise, or add
to maleate to a greater degree than the radical anion II.
Acknowledgements
This study was supported in part by a grant from the
Budgeting and Planning Committee of The Council of
Higher Education and the Israel Atomic Energy Com-
mission. D.M. wishes to express his thanks to Mrs. Irene
Evans for her ongoing interest and support.
Looking at the results for the fumarate system it is obvi-
ous that G(-fumarate) increases with the increase in pH.
This result seems surprising as G(-maleate) is pH inde-
pendent. A plausible explanation of this observation is
that the yield of the reactions:
References and notes
.ꢀ
ꢀ
ꢀ
.
CO2 þmaleate ! ðI=IIþCO2Þ= CHðCO2 ÞCHðCO2 Þ2
.ꢀ
ꢀ
ꢀ
.
1. Schutz, O.; Cohen, H.; Zilbermann, I.; Herscu-Kluska, R.;
Meyerstein, D. Unpublished results.
CO2 þfumarate ! ðIII=IVþCO2Þ= CHðCO2 ÞCHðCO2 Þ2
2. Raznoshik, H.; Maimon, E.; Zilbermann, I.; Matana, Y.;
Cohen, H.; Meyerstein, D. Unpublished results.
3. Neta, P. J. Phys. Chem. 1971, 75, 2570–2574.
4. Anderson, N. H.; Dobbs, A. J.; Edge, D. J.; Norman, R.
O. C.; West, P. R. J. Chem. Soc. (B) 1971, 1004–1008.
5. Hayon, E.; Simic, M. J. Am. Chem. Soc. 1973, 95, 2433–
2439.
is similar, if not identical. Then the difference between
G(-fumarate) and G(-maleate) observed at each pH is
attributed to the reaction:
H2O
2III=2IV=ðIII þ IVÞ ! fumarate þ succinate
As fumarate is thermodynamically more stable than
maleate,13 the yield of maleate is expected to be small
as observed. (We have no explanation for the slight,
though significant, increase in G(-maleate) with the
increase in pH.) According to this assumption, the G
yields of fumarate in the latter reaction are 2.9 0.5
and 1.5 1.0 at pH 5.3 and 7.0, respectively, in the He
saturated solutions. Surprisingly, these G yields are iden-
6. Neta, P.; Fessenden, R. W. J. Phys. Chem. 1972, 76, 1957–
1961.
7. Product analysis was performed by HPLC (Waters, Delta
600 model) with a Waters 996 photodiode array detector
capable of measuring in the 190–800 nm range. Analysis
was carried out with an Ultrasphere RP-18 Beckman
column (250 mm · 4.6 mm · 5 lm) using a mobile phase
consisting of 99% water (pH 2.8 with phosphoric acid) and

1096
O. Schutz, D. Meyerstein / Tetrahedron Letters 47 (2006) 1093–1096
1% methanol. The flow rate was 0.8 ml/min and the 10. Wardman, P. J. Phys. Chem. Ref. Data 1989, 18, 1637–
injection volume was 20 ll. The samples were acidified
prior to injection into the HPLC with phosphoric acid to
pH 2.0. Detection was performed at 210 nm and the
samples were identified from spectra and retention times.
1755.
11. Shandalov, E.; Zilbermann, I.; Maimon, E.; Nahmani, Y.;
Cohen, H.; Adar, E.; Meyerstein, D. Tetrahedron Lett.
2004, 45, 989–992.
8. Matheson, M. S.; Dorfman, L. M. Pulse Radiolysis; M.I.T
Press: Cambridge, MA, 1969.
9. Buxton, G. V.; Greenstock, C. L.; Helman, W. P.; Ross,
A. B. J. Phys. Chem. Ref. Data 1988, 17, 513–886.
12. Swallow, A. J. An Introduction to Radiation Chemistry;
Longman Gr. Ltd.: London, 1973, pp 246–264.
13. Davies, M.; Evans, F. P. Trans. Faraday Soc. 1956, 52, 74–
80.