Anaerobic oxidation of dopamine by iron(III)

Article abstract of DOI:10.1039/a701054k

Iron(III) [in the form of Fe(OH)²⁺] reacted reversibly in acid aqueous solution with dopamine, 2-(3,4-dihydroxyphenyl)ethylamine (H₂LH₊, in which the phenolic protons are written to the left of L) to give the complex ion Fe(LH)²⁺. This species then decomposed to yield iron(II) and a semiquinone, which in turn is oxidised further to a quinone. The latter cyclised to form leucodopaminochrome (indoline-5,6-diol), which was finally oxidised by iron(III) to pink dopaminochrome (6-hydroxy-3H-indol-5-one), presumably via another semiquinone. The rate of appearance and disappearance of the complex and of the ortho-quinone were separately followed by stopped-flow photometric methods. Mechanisms are proposed for the various steps and these are supported by measurements at varying ionic strengths. Rate constants for the reversible formation of the iron-dopamine complex have been evaluated [k₁ = (2.09 ± 0.05) × 10³ and k_-1 = 23 ± 2 dm³ mol^-1 s^-1]. The rate of decomposition of the protonated complex to yield iron(II) and the semiquinone was established as k₂ = 0.23 ± 0.02 s^-1 and K_M^H = 33 ± 0.9 dm³ mol^-1 [for the protonation of Fe(LH)²⁺]. The stability constant of the Fe(LH)²⁺ complex has been calculated (log K₁^M = 21.14) and ε_max is 1260 dm³ mol^-1 cm^-1 at 700 nm. The effect of chloride on the rate of complex formation at low pH has been explained by the fact that FeCl²⁺ also reacts with dopamine (k_Cl = 148 ± 7 dm³ mol^-1 s^-1) to form the complex but that this is predominantly reversible via the non-chloride route at low pH values. The stability constant for FeCl²⁺ formation (a constant not readily accessible by standard methods) was extracted from the data (log K₁^Cl = 1.53). The rate of disappearance of the quinone enabled the ring-closure reaction (i.e. the formation of the indole) to be followed and the mechanism established. All measurements were carried out at 25°C in solutions of ionic strength 0.10 mol dm^-3 (KNO₃) except for ionic strength dependence studies.

Full text of DOI:10.1039/a701054k

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Anaerobic oxidation of dopamine by iron(III)
a
a
b
,a
Usama El-Ayaan, Erwin Herlinger, Reginald F. Jameson and Wolfgang Linert *
a
Institute of Inorganic Chemistry, Technical University of Vienna, Getreidemarkt-9/153,
A-1060 Vienna, Austria
b
Department of Chemistry, The University, Dundee, UK DD1 4HN
2
ϩ
Iron() [in the form of Fe(OH) ] reacted reversibly in acid aqueous solution with dopamine, 2-(3,4-dihydroxy-
ϩ
phenyl)ethylamine (H LH , in which the phenolic protons are written to the left of L) to give the complex ion
2
2
ϩ
Fe(LH) . This species then decomposed to yield iron() and a semiquinone, which in turn is oxidised further to
a quinone. The latter cyclised to form leucodopaminochrome (indoline-5,6-diol), which was finally oxidised by
iron() to pink dopaminochrome (6-hydroxy-3H-indol-5-one), presumably via another semiquinone. The rate of
appearance and disappearance of the complex and of the ortho-quinone were separately followed by stopped-flow
photometric methods. Mechanisms are proposed for the various steps and these are supported by measurements
at varying ionic strengths. Rate constants for the reversible formation of the iron–dopamine complex have been
3
3
Ϫ1 Ϫ1
evaluated [k = (2.09 ± 0.05) × 10 and k = 23 ± 2 dm mol s ]. The rate of decomposition of the protonated
1
Ϫ1
Ϫ1
H
3
complex to yield iron() and the semiquinone was established as k = 0.23 ± 0.02 s and KM = 33 ± 0.9 dm
2
Ϫ1
2ϩ
2ϩ
mol [for the protonation of Fe(LH) ]. The stability constant of the Fe(LH) complex has been calculated (log
M
3
Ϫ1
Ϫ1
K1 = 21.14) and εmax is 1260 dm mol cm at 700 nm. The effect of chloride on the rate of complex formation
2
ϩ
3
Ϫ1 Ϫ1
at low pH has been explained by the fact that FeCl also reacts with dopamine (kCl = 148 ± 7 dm mol s ) to
form the complex but that this is predominantly reversible via the non-chloride route at low pH values. The
stability constant for FeCl formation (a constant not readily accessible by standard methods) was extracted from
the data (log K1 = 1.53). The rate of disappearance of the quinone enabled the ring-closure reaction (i.e. the
formation of the indole) to be followed and the mechanism established. All measurements were carried out at
2
ϩ
Cl
Ϫ3
2
5 ЊC in solutions of ionic strength 0.10 mol dm (KNO ) except for ionic strength dependence studies.
3
Brightly coloured complexes of catechols with iron() are
HO
O–
k1obs
Fe3+
+
Fe3+
O–
well known and often used as qualitative analytical tests. These
NH3+
NH3+
1
,2
colours are, however, not stable and slowly fade. This can be
ascribed to an internal electron transfer within the complexes
which yields iron() and the respective semiquinone; the latter
is unstable with respect to further oxidation (to the quinone).
The quinones of the catecholamines are, however, able to react
HO
Dopamine
Iron(III) complex
k2obs
–Fe2+
3
–5
further
(via an internal Michael addition) to form indole
O
O
O
O
+
Fe3+
compounds. These can usually be oxidised further to yield the
pink aminochromes. How this is related to the present work is
summarised in Scheme 1.
NH3+
NH3+
Quinone
Semiquinone
k3obs
Experimental
Dopamine [4-(2-aminoethyl)benzene-1,2-diol] hydrochloride
HO
HO
2Fe3+
O
+
(
C H NO ؒHCl) was supplied by Sigma Chemical Co. and
8 11 2
used without further purification. The chloride was converted
when necessary into the nitrate form by means of an ion-
exchange column. Solutions of the required pH were made up
from deoxygenated stock solutions of dopamine and of iron()
N
N
HO
H
Leucodopaminochrome
Dopaminochrome
Scheme 1 Overall route of oxidation of dopamine
(as nitrate nonahydrate, Merck) that contained calculated
amounts of HNO3 and KNO3 to maintain the final ionic
strength at 0.100 mol dm . Some experiments were carried out
Ϫ3
the quinone were followed at 380 nm. [All kinetic runs were
performed with dopamine in large excess over iron() in order
to maintain pseudo-first-order kinetics.]
with KCl or KBr as supporting electrolyte as well as various
nitrate–halide mixtures. In order to investigate the dependence
ϩ
ϩ
on ionic strength of these reactions, various salts of Li , Na ,
ϩ
2ϩ
K
and Mg were used. The pH was measured immediately
Results and Discussion
after each kinetic run with a WTW pH 521 pH meter and the
Complex formation
ϩ
6
[
[
H ] was calculated by use of the empirical relationship
ϩ
Ϫ[(pH Ϫ 0.131)/0.984]
H ] = 10
. Since the iron concentration was kept
Above pH 1.8 the formation reaction of the complex between
ϩ
low, the change of pH due to H released on complex form-
ation was negligible.
iron() and dopamine is accurately first order in both [Fe] and
T
[L] , but at lower pH the rate varies with, but is not first order in
T
The appearance and the disappearance of the (green) com-
plex were followed at 700 nm with a Bio-sequential SX-17MV
sequential stopped-flow ASVD spectrofluorimeter, and yielded
[L] . This behaviour has been found for the closely related
T
catecholamines adrenaline and dopa [3-(3,4-dihydroxyphenyl)-
3
,7
-alanine] and arises from reversibility of the reaction (as is
obs
obs
observed pseudo-first-order rate constants, k1
and k2
explained below).
Typical first-order rate constants, k1 , for complex form-
obs
respectively. Similarly, the appearance and the disappearance of
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818
2813

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obs
Table 1 Typical values of k1
3
ϩ
5
1
0 [H ]/mol
10 [Fe] /mol
T
Ϫ3
Ϫ3
Ϫ3
obs Ϫ1
obs
ϩ
ϩ
2
[
L] /mol dm
pH
dm
dm
k1 /s
k1 /[H ]
[L] /[H ]
T
T
0
.01
0.79
186
120
115
50
10
25
10
25
10
50
5
4.53
3.13
2.40
2.65
2.05
2.11
1.78
1.55
1.66
1.66
24.4
26.1
20.9
29.1
29.0
31.9
28.8
27.6
41.7
45.7
0.289
0.694
0.756
1.20
1.99
2.29
2.63
3.17
6.31
7.59
0
1
1
1
1
1
1
1
1
.98
.00
.10
.21
.24
.27
.31
.46
.50
91.2
70.8
66.1
61.7
56.2
39.8
36.3
25
10
1
1
2
2
2
.68
.75
.00
.13
.37
24.0
20.4
11.5
8.51
4.90
50
10
10
50
100
1.78
2.01
2.48
3.55
5.75
0
0
.02
.04
0.98
120
67.6
50.1
38.0
10
10
100
10
3.26
2.51
2.44
2.55
27.2
37.1
48.7
67.1
1.39
4.38
7.97
13.9
1
1
1
.23
.36
.48
1.23
67.6
47.9
45.7
39.8
37.2
10
10
50
50
10
3.45
3.99
3.76
4.09
4.30
51.0
83.3
82.3
102
8.75
17.4
19.2
25.3
28.9
1
1
1
1
.38
.40
.46
.49
116
restriction would not apply, of course, if the reactions were
parallel, but the data strongly suggest that any contribution
3
ϩ
from the reaction of Fe with HLH must be extremely small
and this conclusion is reinforced by the dependence of the rate
on ionic strength (see below).
At the pH under consideration, the observed rate law can,
therefore, be written as in equation (3), where the subscript eq
obs
d[coloured complex]/dt = k1 ([Fe]T,o Ϫ [Fe]T,eq
)
(3)
2
ϩ
ϩ
2ϩ
ϩ
=
k [Fe(OH) ][H LH ] Ϫ k [Fe(HL) ][H ] (4)
1 2 Ϫ1
implies the value of the quantity at equilibrium. Application of
equilibrium (2) then leads to equation (4). The total uncom-
plexed iron(), [Fe] , is given by equation (5), and the equi-
T
librium condition (6) must also be valid.
obs
Fig. 1 Variation with pH of the observed rate constants, k1 , for the
3ϩ
2ϩ
[
Fe] = [Fe ] ϩ [Fe(OH) ]
(5)
Ϫ3
T
formation of the iron()–dopamine complex ([L] = 0.01 mol dm
,
T
various [Fe] values). Data from Table 1
T
2
ϩ
ϩ
2ϩ
ϩ
k1/kϪ1 = [Fe(LH) ] [H ]/[Fe(OH) ] [H LH ] (6)
eq
eq
2
ation are given in Table 1 and illustrated in Fig. 1. The plot of
k1 vs. pH (Fig. 1) shows that the rate passes through a distinct
2
ϩ
obs
However, since (i) [Fe(LH) ] = ([Fe]T, oϩ Ϫ [Fe]T,eq), (ii)
eq
dopamine is used in great excess giving [H LH ] ≈ [L] and (iii)
minimum at a pH of about 1.5. The acceleration with decreas-
2
T
ϩ
2ϩ
only those data obtained below pH ≈ 1.6 are considered, then
FeOH ϩ
ing [H ] at higher pH is the result of Fe(OH) being far more
3
ϩ
K
[H ] ӷ 1 and equation (6) becomes (7). Inserting this
reactive than Fe [equation (1) shows the relationship between
FeOH
ϩ 2
FeOH
ϩ 2
2
ϩ
ϩ
3ϩ
FeOH
[Fe]T,eq = kϪ1
K
[H ] [Fe] /(k [L] ϩ kϪ1K
[H ] ) (7)
Fe(OH) ϩ H
Fe ; log K
= 2.82 (1)
T,o
1
T
8
,9
FeOH
3
Ϫ1
result and the above assumptions into the rate law leads, after
comparison with the observed rate law (3), to equation (8).
these two species and the value of K
= 660 dm mol ]
and to explain the opposite effect at lower pH it is necessary to
take reversibility into account. The complex is formed accord-
ing to reaction (2). Note that ‘proton ambiguity’ is involved
k1obs = (k /K
FeOH
)([L] /[H ]) ϩ k [H ]
ϩ
ϩ
(8)
1
T
Ϫ1
obs
ϩ
ϩ 2
k
1
Thus a plot of k1 /[H ] vs. [L] /[H ] should be linear with
T
FeOH
2
ϩ
ϩ
Fe(OH) ϩ H LH
2
k
Ϫ1
intercept corresponding to kϪ1 and a slope of k /K
illustrated in Fig. 2 and, using K
results k = (2.09 ± 0.05) × 10 dm mol
. This is
1
2
ϩ
ϩ
3ϩ
FeOH
3
Ϫ1
Fe(LH) ϩ H or [Fe(HLH) ] (2)
= 660 dm mol , yields the
3
3
Ϫ1 Ϫ1
s
and kϪ1 = 23 ± 2
1
3
ϩ
3
Ϫ1 Ϫ1
here and implies that the reaction of Fe with HLH would
equally well fit the data, but this would lead to an improbably
high value for the rate constant (ca. 10 dm mol s ). This
dm mol s . The ratio k /k , thus enables the stability con-
1 Ϫ1
2ϩ
stant for the formation of Fe(LH) to be calculated from the
1
1
3
Ϫ1 Ϫ1
M
H
FeOH
H
relationship K1 = k1β2 /kϪ1
K
(where β2 is the micro-
2
814
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818

View Article Online
obs
Ϫ
Ϫ3
obs
Ϫ
Ϫ3
Ϫ3
Table 2 Variation of k1 with [Cl ] (pH 1.27, [L] = 0.01 mol dm
)
Table 3 Values of kCl for [Cl ] = 0.05 mol dm
T
Ϫ
Ϫ3
3
ϩ
[
Cl ]/mol dm
0.025 0.030 0.0325 0.045
0.0575 0.100
6.12 9.44
10 [H ]/mol
obs Ϫ1
Ϫ3
obs Ϫ1
k1 /s
3.60
4.09
4.14
5.32
pH
dm
[L] /mol dm
kCl /s
T
1
1
1
1
.07
97.7
79.4
57.5
42.7
0.005
6.28
6.91
8.33
0
0
0
.01
.02
.04
10.2
.16
.30
.43
0.005
5.38
5.91
7.56
—
0
0
0
.01
.02
.04
0.005
4.18
4.62
5.65
—
0
0
0
.01
.02
.04
0.005
3.19
3.72
5.14
7.22
0
0
0
.01
.02
.04
obs
ϩ
ϩ 2
Fig. 2 Plot of k1 /[H ] vs. [L] /[H ] for values obtained below pH 1.5
T
(data from Table 1)
constant for the protonation of the phenolic groups of the
H
dopamine; the value log β2 = 22.00 was used). A value of log
M
K1 = 21.14 was obtained, and accepting this value enabled the
3
Ϫ1
Ϫ1
molar absorption, εmax = 1260 dm mol cm at 700 nm, to be
calculated.
Effect of chloride ions on the rate of complex formation. At
pH values below 1.5 the presence of chloride ions has a marked
effect on the rate of complex formation. The results in Table 2
obs
show clearly that the rate constant, k1 , is directly pro-
Ϫ
portional to [Cl ]. Furthermore, when expression (8) is applied
to data obtained in chloride media the rather surprising result
is obtained that k is unaffected, whereas the reverse reaction,
1
Ϫ
represented by kϪ1, is apparently proportional to [Cl ]. This
obs
Ϫ
Ϫ3
3
ϩ
Fig. 3 Plots of kCl vs. [L] for [Cl ] = 0.05 mol dm and 10 [H ] =
T
2
ϩ
Ϫ3
effect can be explained by assuming that the species FeCl
97.7 (᭺), 79.4 (᭝), 57.5 (ᮀ) and 42.7 (᭞) mol dm (data from Table 3)
ϩ
is also able to react with H LH , equation (9), and since (9) is
2
2
ϩ
3
Ϫ1
(
the formation constant for FeCl ) is 34 dm mol , i.e. log
Cl
k
Cl
K1 = 1.53. This constant is extremely difficult to obtain by
other methods and the literature values vary over a vast range,
but kinetically obtained values of stability constants are, in
2
ϩ
ϩ
2ϩ
Ϫ
ϩ
FeCl ϩ H LH
Fe(LH) ϩ Cl ϩ 2H
(9)
2
predominantly reversible via the non-chloride route at low pH
values [equation (2)], resulting in the apparent effect of chloride
ions of exclusively enhancing the reverse reaction.
general, very reliable. The rate constant, k , for the reaction of
Cl
2ϩ
ϩ
FeCl with H LH was obtained from the slopes of these lines
2
FeOH
ϩ
Cl
Ϫ
Cl
Ϫ
{
slope = (k /K
[H ] ϩ k K [Cl ])/(1 ϩ K [Cl ]) for each
Cl 1 1
3 Ϫ1 Ϫ1
obs
1
The increase of k1 with increased reverse reaction is a result
ϩ
[
H ]}: a mean value of 148 ± 7 dm mol
s
was accepted.
of the mathematical behaviour of reverse first-order reactions
obs
10
for which k1 = k ϩ kϪ1. Allowance must also be made
1
The addition of bromide ions. Unlike chloride ions, bromide
had no discernible effect on the rate.
for the fact that [Fe]T must now be written as in equation
10). By neglecting the value of [Fe(OH) ] with respect to
2
ϩ
(
3
ϩ
2ϩ
2ϩ
Electron transfer in the coloured complex
[
Fe] = [Fe ] ϩ [FeCl ] ϩ [Fe(OH) ]
(10)
T
2
ϩ
The rate of decomposition of Fe(LH) passes through a min-
2
ϩ
Cl
[
FeCl ], equation (10) becomes (11) where K is the formation
imum with pH (pHmin ≈ 1.8), is independent of [L] at lower
1
T
Ϫ
pH, and independent of [Cl ]. Now the rate of disappearance
3
ϩ
2ϩ
3ϩ
Cl
Ϫ
[
Fe] = [Fe ] ϩ [FeCl ] = [Fe ](1 ϩ K [Cl ]) (11)
of the coloured complex monitors the rate of disappearance of
T
1
[
Fe] and is therefore given by equation (13), and typical values
T
obs
2
ϩ
constant for FeCl . Thus, in the presence of chloride, equation
of k2 for pH < 1.75 are given in Table 4.
obs
(
8) must be replaced by (12). Plots of kCl vs. [L] at constant
T
obs
Ϫd[coloured complex]/dt = Ϫd[Fe] /dt = k [Fe]T (13)
T
2
obs
Cl
Ϫ
FeOH
ϩ
Cl
ϩ
kCl = k [L] /{(1 ϩ K [Cl ])K
[H ]} ϩ k [H ] ϩ
Ϫ1
1
T
1
Cl
Ϫ
Cl
Ϫ
obs
k K1 [Cl ][L] /(1 ϩ K [Cl ]) (12)
Since k
2
increases with decrease in pH it can be assumed
3ϩ
Cl
T
1
that it is the protonated complex, Fe(HLH) , that is the reactive
species. In this respect it is interesting that there is X-ray
spectroscopic evidence that protonated catechols act as mono-
dentate ligands towards iron(), while deprotonated ones
chelate. The complex Fe(LH) can be protonated, yielding
Ϫ
ϩ
[
Cl ] and [H ] should be linear and this is confirmed by Fig. 3
and Table 3, in which data for several [H ] values with
Cl ] = 0.05 mol dm are presented. These plots have inter-
ϩ
Ϫ
Ϫ3
11
[
Cl
ϩ
Cl
Ϫ1
Cl
3
12
2ϩ
cepts = k
[H ] from which a mean value of k
was obtained and since kϪ1 = kϪ1(1 ϩ K1 [Cl ]), K
= 62 dm
Ϫ1
Ϫ1 Ϫ1
Cl
Ϫ
Cl
3ϩ
mol
s
Fe(HLH) , in which the dopamine presumably acts as a mono-
1
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818
2815

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obs
Table 4 Typical values of k2 for pH < 1.75
3
ϩ
5
1
0 [H ]/mol
10 [Fe] /mol
T
Ϫ3
Ϫ3
Ϫ3
2
obs Ϫ1
obs
ϩ
Ϫ1
3
Ϫ1
pH
dm
dm
[L] /mol dm
10 k2 /s
(1/2 k2 )/s
[H ] /dm mol
T
1
1
1
1
1
1
1
.20
72.4
47.9
46.7
42.7
33.9
27.5
22.4
25
10
10
5
10
10
5
0.02
0.01
0.04
0.02
0.02
0.01
0.04
8.04
6.94
6.43
6.76
6.03
5.63
4.91
6.22
7.20
7.78
7.40
8.29
8.88
10.2
13.8
20.9
21.8
23.4
29.5
36.5
44.2
.38
.39
.43
.53
.62
.71
dentate ligand, and electron transfer takes place within this
protonated complex.
Table 5 Variation of log (k/k
0
) with ionic strength (pH 1.50,
Ϫ3
[
L] = 0.04 mol dm
)
T
Furthermore, the decomposition of the coloured complexes
can be treated assuming that they are formed in a rapid
pre-equilibrium since the ratio k1 :k2 was at least 50:1,
i.e. the reaction can be written as in equation (14). Since the
¹
¹
obs
obs
I �² / mol �²
log (k1
/
log (k
k2,0 )
/
2
Ϫ₃
Ϫ3
₂
�
obs
obs
Salt
I/mol dm
dm
k1,0
)
obs
obs
LiCl
0.30
0.55
0.63
0.71
0.77
0.89
1.00
1.21
1.26
1.43
1.55
1.76
2.04
Ϫ0.09
0.05
0.06
0.17
0.17
0.02
0
0
0
0
1
.40
.50
.60
.80
.00
k
2
2
ϩ
ϩ
2ϩ
ϩ
Fe(OH) ϩ H LH
Fe(LH) ϩ H
2
II
Fe ϩ semiquinone (14)
3
ϩ
NaCl
0.30
0.55
0.63
0.71
0.77
0.89
1.00
1.09
1.22
1.41
1.49
1.85
1.93
0.11
0.19
0.23
0.12
0.12
0.09
equilibrium constant is very large, it is k [Fe(HLH) ] that is
2
0
0
0
.40
.50
.60
being followed and hence the rate equation becomes (15) in
3
ϩ
Ϫd[FeL] /dt = k [Fe(HLH) ]
(15)
T
2
0.80
.00
1
which the total concentration of complex, [FeL] , is given by
16) in which the protonation constant KM = [Fe(HLH) ]/
T
H
3ϩ
(
KNO3
0.25
.35
0.45
0.5
1.01
1.12
1.36
1.37
1.70
1.75
Ϫ0.15
Ϫ0.09
0.01
0.03
0.05
0
0.59
0.67
0.74
0.87
0.97
3
ϩ
2ϩ
[
FeL] = [Fe(HLH) ] ϩ [Fe(LH) ] =
T
0
0
0
.55
.75
.95
3
ϩ
H
ϩ
H
ϩ
[
Fe(HLH) ](1 ϩ K [H ])/K [H ] (16)
M M
0.15
2
ϩ
ϩ
[
Fe(LH) ][H ]. Introducing equation (16) into (15) yields (17).
MgCl2
0.75
1.05
0.87
1.02
1.16
1.28
1.50
1.69
1.75
2.19
2.22
2.55
3.01
3.34
0.15
0.11
0.14
0.25
0.27
0.31
H
ϩ
H
ϩ
Ϫd[FeL] /dt = k K [H ]/(1 ϩ K [H ])[FeL]T (17)
T
2
M
M
1
1
.35
.65
The semiquinone produced, however, reacts rapidly with
another Fe to yield the quinone and Fe making d[Fe] /dt =
d[FeL] /dt and hence expressions (18) and (19) follow. Thus a
3
ϩ
2ϩ
2.25
.85
T
2
2
T
obs
H
ϩ
H
ϩ
2
k2 = k K [H ]/(1 ϩ K [H ])
(18)
(19)
2
M
M
obs
H
ϩ
1
/2k2 = (1/k K [H ]) ϩ (1/k )
2
M
2
obs
ϩ
H
plot of 1/2k2 vs. 1/[H ] has slope 1/k K and intercept 1/k .
2
M
2
3
Ϫ1
H
From this plot k = 0.23 ± 0.02 s and k K = 7.56 ± 0.1 dm
2
2
M
Ϫ1 Ϫ1
H
3
Ϫ1
mol Hs which yields KM = 33 ± 0.9 dm mol . This value of
k2KM is identical to that obtained (using high pH data) for the
3
dopa system and shows that the redox potentials for the reduc-
tion of dopa and of dopamine to the respective semiquinones
must be almost identical. These one-electron redox potentials
1
3
have been shown to have identical values of 18 mV, calculated
by using the value of hydroquinone as a reference.
1
4
In a parallel study of the noradrenaline–iron() system
there is evidence for a small outer-sphere contribution to the
2
ϩ
redox reaction at low pH [vis-à-vis Fe(OH) reacting with
ϩ
H LH to yield directly iron() and semiquinone]. However, it
2
has not been possible to confirm any such effect in the
dopamine–iron() system, although from the data obtained it
certainly cannot be ruled out entirely.
obs
obs
¹
Fig. 4 Plot of log (k1 /k1,0 ) vs. I �² showing that z z = 2 [see Table 5
a
b
and equation (19)]. Salts: ᭺, LiCl; ᭝, NaCl; ᮀ, KNO ; ᭞, MgCl ;
3
2
theoretical line of slope 2.04
Ionic strength effects
obs
obs
Both k1 and k2 were measured over a range of ionic
strengths using a variety of salts and Table 5 gives some values
The kinetic salt effect on two reacting species A and B with
obs
obs
obs
obs
¹
of log (k1 /k1,0 ) obtained. A plot of log (k1 /k1,0 ) vs. I is
�
²
charges z and z respectively can be expressed in terms of the
a
b
shown in Fig. 5 and is seen to correspond satisfactorily with the
theoretical slope of 2.04 for z z = ϩ2 which is consistent with
Brønsted relationship (20) in which the constant A is 0.51 for
aqueous solutions at 25 ЊC.
a
b
the formulation of the formation and reverse reactions (4) and
¹
obs
obs
log k = log k ϩ 2Az z I
�
²
(20)
(9). Table 5 also includes values of log (k2 /k2,0 ) and it is seen
0
a
b
2
816
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818

View Article Online
¹
3
that these vary little with I �² which confirms the postulate of
iron()–dopa system for comparison purposes, see below].
The results strongly suggest that two quinone species are
involved, one being protonated [equation (22)]. This must imply
that protonation of the quinone function takes place at low pH.
We further assume that deprotonation at the amino site is a
requirement for cyclisation, and because the protonation con-
2
ϩ
Fe(HLH) reacting alone (or involving the participation of a
solvent, i.e. water, molecule?).
Formation of the indole ring
The quinones of catecholamines such as dopamine spon-
taneously cyclise via an internal Michael addition to form
the UV-transparent leucodopaminochrome (indoline-5,6-diol)
H
stant of this functional group is very high [log KN = log(ka/
kϪa) = 9.95] this (deprotonation) step is relatively slow and must
be taken into account. These ideas are summarised in Scheme 2.
The experimental results can be interpreted on the basis of
Scheme 2 and the associated equations (22) and (23). Under
(
see Scheme 1). The kinetics of this cyclisation reaction for
dopamine was followed by monitoring the quinone at 380 nm.
Unfortunately this was only possible up to a pH of about 3, at
which point the absorption of the iron() complexes begins to
interfere. However, work in these laboratories has shown that
the quinone can be produced at higher pH by using periodate as
the oxidant enabling measurements up to a pH of 7.
H
ϩ
1
5
Ϫd[Q]
T
/dt = kcyc[Q] ϩ kcyc [HQ ]
(22)
(23)
H
H
ϩ
=
(kcyc ϩ kcyc KQ [H ])[Q]
The rate of disappearance of the quinone follows the rate
law (21) and typical results are summarised in Table 6 and
reaction conditions [Q] will reach a steady state, equation (24)
ϩ
ϩ
obs
d[Q]/dt = 0 = kϪa[QH ] Ϫ k
a
[Q][H ] Ϫ kcyc[Q] (24)
Ϫd[Q] /dt = k3 [Q]T
(21)
T
or (25). However, the total quinone concentration, [Q] , is given
T
illustrated in Fig. 6 [which also includes the results for the
ϩ
H
ϩ
[
Q] = [QH ]/{K [H ] ϩ (kcyc/kϪa)}
(25)
N
by equation (26) and the combination of (23), (25) and (26)
ϩ
2ϩ
ϩ
H
ϩ
[
Q] = [QH ] ϩ [HQH ] = [QH ](1 ϩ K [H ]) (26)
T
Q
and comparison with (21) leads to (27). The solution of
obs
H
H
ϩ
k3 = (kcyc ϩ kcyc KQ [H ])/
H
ϩ
Ϫ1
H
ϩ
{
(KN [H ] ϩ kcyckϪa )(1 ϩ KQ [H ])}
(27)
H
H
equation (27) enables values of kcyc, kcyc , and KQ to be
obtained and these are given in Table 7.
Linert et al. in their study of the iron()–dopa system had
previously ascribed the protonation of the dopaquinone to pro-
obs
Fig. 5 Observed rates of cyclisation of dopaminoquinone (log k3 vs.
3
3
ϩ
pH) with theoretical curve (derivation in text): ᭡, values from Fe
oxidation; ᭿, oxidation with periodate (see Table 6). The theoretical
curve for dopa (----) is included for comparison
tonation of the carboxyl group and therefore assigned the value
O
O
O
O
obs
k–a
ka
Table 6 Typical values for the observed rate constants, k3 , for indole
formation (ring-closure reaction) following oxidation of the dopamine
to the quinone
H3N
QH+
H2N
kcyc
3
ϩ
Q
Using Fe as oxidant
Using periodate as oxidant
HO
HO
obs
obs
pH
Ϫlog k3
pH
Ϫlog k3
0
0
1
1
1
1
2
2
.55
3.27
3.27
3.10
3.01
2.95
3.01
2.99
3.03
2.0
2.5
3.0
3.6
3.8
4.1
4.3
4.6
2.95
2.90
2.85
3.31
2.76
2.68
2.85
2.77
1.77
1.10
0.88
0.24
KQH
KQH
N
H
.75
.06
.66
.71
.75
.14
.45
Leucodopaminochrome
kHcyc
O
k–a
ka
O
H+
H+
5
6
6
6
.7
.3
.7
.85
O
O
H3N
H2N
HQ+
HQH2+
Scheme 2 Details of ring-closure reaction
Table 7 Comparison of results obtained for dopamine and dopa systems
(a) Oxidation of the catecholamines
log KN
H
H
M
Ϫ1
Ϫ1
Ϫ1
H
3
Ϫ1 Ϫ1
log β2
log K1
k1/s
kϪ1/s
k2/s
k2KM /dm mol
s
Dopamine
dopa
9.95
9.20
22.00
22.20
21.14
21.43
2094
2100
23
22
0.23
0.3
7.56
7.52
(
b) Formation of leucoaminochrome from quinone (ring-closure reaction)
Ϫ1
H
Ϫ1
H
Ϫ1
kϪa/s
log KQ
kcyc/s
kcyc /s
2
6
Dopaminequinone
Dopaquinone
6.33
5.42
1.04
1.13
3.48 × 102
3.16 × 10
1.12 × 105
5.51 × 10
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818
2817

View Article Online
2
.22
3
Ϫ1
H
H
H
1
0
dm mol to KQ (i.e. identifying KQ with K4 for
G. N. L. Jameson for their data on the ring closure at higher pH
dopa). In the light of the present work this assignment is obvi-
ously erroneous and so Table 7 includes the results for the dopa
system recalculated by the same method employed here: the
agreement between the two (chemically very similar) systems is
highly satisfactory. Reference to equation (27) shows that the
values.
References
1 E. Mentasti, E. Pelizzetti and C. Baiocchi, J. Inorg. Nucl. Chem.,
1975, 38, 2017.
obs
displacement of the two log k3 vs. pH curves for dopa and
2
E. Mentasti, E. Pelizzetti and E. Pramaura, J. Inorg. Nucl. Chem.,
975, 37, 1733.
W. Linert, R. F. Jameson and E. Herlinger, Inorg. Chim. Acta, 1991,
87, 239.
dopamine (Fig. 6) arises almost exclusively from the differences
in the protonation constants for the respective amino groups.
1
3
3
Furthermore, Linert et al. had not allowed for the reverse reac-
1
tion of complex formation in their calculation of k ; this has
now been done in Table 7 by using their published data at low
pH.
Finally, the close correspondence between the dopa and
dopamine systems is emphasised by Table 7 in which the pres-
ent results for the formation of the coloured complexes and
their subsequent redox decomposition are contrasted with
those obtained for the interaction of iron() with dopa.
4 J. Harley-Mason, J. Chem. Soc., 1950, 1276.
5 M. D. Hawley, S. V. Tatawawadi, S. Piekarskiani and R. N. Adams,
J. Am. Chem. Soc., 1967, 89, 447.
1
6
7
J. E. Gorton, Ph.D. Thesis, University of St. Andrews, 1968.
W. Linert, E. Herlinger and R. F. Jameson, J. Chem. Soc., Perkin
Trans. 2, 1993, 2435.
8
R. F. Jameson, W. Linert, A. Tschinkowitz and V. Gutmann,
J. Chem. Soc., Dalton Trans., 1988, 943.
9 E. Mentasti, E. Pelizzetti and G. Saini, J. Inorg. Nucl. Chem., 1976,
8, 785.
3
1
0 R. Schmid and V. N. Sapunov, Non-Formal Kinetics, Monograph in
Modern Chemistry 14, Verlag Chemie, Weinheim, 1982, p. 21.
1 R. H. Heistand, A. L. Roe and L. Que, Inorg. Chem., 1982, 21, 676.
2 R. B. Lauffer, R. H. Heistand and L. Que, Inorg. Chem., 1983, 22,
50.
Acknowledgements
1
1
Thanks are due to the Fonds zur Förderung der Wissen-
schaftlichen Forschung in Österreich (Project 11218-CHE) and
the Jubiläumsfonds der Österreichische Nationalbank. Usama
El-Ayaan thanks the Austrian Academic Exchange Service for
supporting his studies in Vienna via the North-South-Dialogue,
and the Department of Chemistry, Faculty of Science,
Mansoura University, Egypt for leave. We thank E. Cotter and
13 S. Steenken and P. Neta, J. Phys. Chem., 1982, 86, 3661.
1
1
4 U. El-Ayaan, R. F. Jameson and W. Linert, unpublished work.
5 E. Cotter, G. N. L. Jameson and W. Linert, unpublished work.
Received 14th February 1997; Paper 7/01054K
2
818
J. Chem. Soc., Dalton Trans., 1997, Pages 2813–2818