A kinetic study of the reaction between noradrenaline and iron(III): An example of parallel inner- and outer-sphere electron transfer

Article abstract of DOI:10.1039/a708639c

In anaerobic acid solution noradrenaline [norepinephrine, 4-(2-amino-1-hydroxyethyl)benzene-1,2-diol, H₂LH⁺ (in which the phenolic protons are written on the left of L)] reacts with iron(III) [in the form of Fe(OH)²⁺] to yield iron(II) and the semiquinone form of noradrenaline which is in turn oxidised rapidly by more iron(III) to 'noradrenoquinone'. This reaction proceeds both directly (i.e. via an 'outer-sphere' reaction) and after prior formation of the complex Fe(LH)²⁺ which then decomposes via intramolecular electron transfer. [The observed rate of formation of the complex (monitored at 714 nm) is faster than the rate of its decomposition by a factor of about 200.] The quinone then cyclises by an intramolecular Michael addition giving the (UV transparent) leuconoradrenochrome (indoline-3,5,6-triol), which is able to react with iron(III) at high pH to give noradrenochrome (3,5-dihydro-3,6-dihydroxy-2H-indol-5-one). At lower pH values the presence of chloride ions shows a marked effect on the rate of complex formation because the species FeCl²⁺ is also able to react with noradrenaline to form the complex although chloride is not involved in the reverse reaction. The stability constant for the formation of FeCl²⁺ (K₁^Cl) was found to be 35, i.e. log K₁^Cl = 1.54 (identical to the value obtained from previous work with dopamine). The ring-closure reaction was studied by following the rate of quinone decomposition monitored at 380 nm, and a mechanism for this cyclisation is proposed. The following rate constants have been evaluated: (i) for the reversible formation of the iron-noradrenaline complex [via Fe(OH)²⁺ + H₂LH⁺] k₁ = 2170 ± 20 dm³ mol^-1 s^-1 and k_-1 = 21 ± 2 dm³ mol^-1 s^-1, from which the stability constant of the Fe(LH)²⁺ complex has been calculated (log K₁^M = 21.2), (ii) rate of formation of the complex via FeCl²⁺ + H₂LH⁺, k_Cl = 48 ± 3 dm³ mol^-1 s^-1, (iii) rate of decomposition of the complex Fe(HLH)³⁺, k₂ = 2.6 ± 0.1 s^-1 [protonation constant for Fe(LH)²⁺, K_M^H = 34 ± 1 dm³ mol^-1], (iv) rate of outer-sphere redox reaction, k_2′ = 100 ± 2 dm³ mol^-1 s^-1, (v) rate of indole formation (ring-closure reaction), k_cyc = 1400 ± 20 s^-1 (for quinone) and k_cyc^H = (2.0 ± 0.1) × 10⁵ s^-1 (for protonated quinone). All measurements were carried out at 25.0°C in solutions of ionic strength 0.10 mol dm^-3 (KNO₃ serving as inert electrolyte).

Full text of DOI:10.1039/a708639c

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A kinetic study of the reaction between noradrenaline and iron(III):
an example of parallel inner- and outer-sphere electron transfer
Usama El-Ayaan,a Reginald F. Jamesonb and Wolfgang Linert*,a
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
In anaerobic acid solution noradrenaline [norepinephrine, 4-(2-amino-1-hydroxyethyl)benzene-1,2-diol, H2LHϩ
(in which the phenolic protons are written on the left of L)] reacts with iron() [in the form of Fe(OH)2ϩ] to
yield iron() and the semiquinone form of noradrenaline which is in turn oxidised rapidly by more iron() to
‘noradrenoquinone’. This reaction proceeds both directly (i.e. via an ‘outer-sphere’ reaction) and after prior
formation of the complex Fe(LH)2ϩ which then decomposes via intramolecular electron transfer. [The observed
rate of formation of the complex (monitored at 714 nm) is faster than the rate of its decomposition by a factor
of about 200.] The quinone then cyclises by an intramolecular Michael addition giving the (UV transparent)
leuconoradrenochrome (indoline-3,5,6-triol), which is able to react with iron() at high pH to give noradreno-
chrome (3,5-dihydro-3,6-dihydroxy-2H-indol-5-one). At lower pH values the presence of chloride ions shows a
marked effect on the rate of complex formation because the species FeCl2ϩ is also able to react with noradrenaline
to form the complex although chloride is not involved in the reverse reaction. The stability constant for the
formation of FeCl2ϩ (K1Cl) was found to be 35, i.e. log K1Cl = 1.54 (identical to the value obtained from previous
work with dopamine). The ring-closure reaction was studied by following the rate of quinone decomposition
monitored at 380 nm, and a mechanism for this cyclisation is proposed. The following rate constants have
been evaluated: (i) for the reversible formation of the iron–noradrenaline complex [via Fe(OH)2ϩ ϩ H2LHϩ]
k1 = 2170 20 dm3 molϪ1 sϪ1 and kϪ1 = 21 2 dm3 molϪ1 sϪ1, from which the stability constant of the Fe(LH)2ϩ
complex has been calculated (log K1M = 21.2), (ii) rate of formation of the complex via FeCl2ϩ ϩ H2LHϩ,
kCl = 48 3 dm3 molϪ1 sϪ1, (iii) rate of decomposition of the complex Fe(HLH)3ϩ, k2 = 2.6 0.1 sϪ1 [protonation
constant for Fe(LH)2ϩ, KMH = 34 1 dm3 molϪ1], (iv) rate of outer-sphere redox reaction, k2Ј = 100 2 dm3 molϪ1
s
Ϫ1, (v) rate of indole formation (ring-closure reaction), kcyc = 1400 20 sϪ1 (for quinone) and kcycH = (2.0 0.1) ×
105 sϪ1 (for protonated quinone). All measurements were carried out at 25.0 ЊC in solutions of ionic strength 0.10
mol dmϪ3 (KNO3 serving as inert electrolyte).
The interactions between iron and the catecholamines are of
special interest because of their involvement in the progression
of Parkinson’s disease. In this respect 6-hydroxydopamine [5-
(2-aminoethyl)benzene-1,2,4-triol] has attracted special atten-
tion because, unlike most of the catecholamine family, no com-
plex with iron() can be detected, but it reacts directly1 with
iron() to form iron() and a semiquinone (i.e. by an ‘outer-
sphere’ electron-transfer reaction). This is almost certainly the
reason that it is capable of extracting iron from ferritin.2 Most
catecholamines (e.g. dopa [3-(3,4-dihydroxyphenyl)alanine],3
dopamine [4-(2-aminoethyl)benzene-1,2-diol],4 and adrenaline
{4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol}5), on
the other hand, initially form a complex with iron() and the
redox reaction then proceeds via internal electron transfer with-
in the complex. This difference in redox behaviour is certainly
related to the one-electron redox potentials of the species
involved, and this would seem to be confirmed by the present
study on noradrenaline which reacts with iron() via both reac-
tions (i.e. by parallel ‘inner-sphere’ and ‘outer-sphere’ electron-
transfer reactions). However, it must be admitted that the values
of the one-electron redox potentials reported by Steenken and
Neta6 do not fully agree with this conclusion, but the very
different conditions under which they were obtained (at high
pH in glycol) makes their relevance uncertain.
which in turn can be protonated at one of the co-ordinated
oxygen atoms7 at which point internal electron transfer takes
place. As stated above, an exception to this rule is found1,8 with
6-hydroxydopamine which does not produce a coloured com-
plex but reacts directly with the iron() to form the p-quinone
(via the semiquinones). It is particularly interesting, therefore,
to see from the present work that noradrenaline exhibits a
relatively small contribution from the ‘outer-sphere’ reaction as
well as the more usual route via complex formation. However
the final product of the redox process at low pH is the yellow-
green noradrenoquinone [formed by rapid reaction of the semi-
quinone with another iron()]. This subsequently cyclises by an
intramolecular Michael condensation to form the UV trans-
parent leuconoradrenochrome (indoline-3,5,6-triol). This can
be further oxidised to yield the pink noradrenochrome (3,5-
dihydro-3,6-dihydroxy-2H-indol-5-one), although this step was
not followed in the present study because it only takes place at a
higher pH than that which we have employed. These steps are
summarised in Scheme 1.
Experimental
Solutions of the required pH were made up from deoxygenated
stock solutions of noradrenaline (supplied as tartrate and con-
verted to nitrate by use of an ion-exchange column) and of
iron() (as nitrate nonahydrate, Merck, p.a.) that contained a
calculated amount of HNO3 and sufficient KNO3 to maintain
the final ionic strength at 0.100 mol dmϪ3. Experiments were
also carried out with solutions containing KCl in order to
investigate the effect of chloride ions on the reaction. The pH
When iron() is added to an acidic solution of noradrenaline
[norepinephrine, 4-(2-amino-1-hydroxyethyl)benzene-1,2-diol]
a dark green colour appears which rapidly fades and can be
restored by the addition of excess iron(). In the present case
this green colour is due to the formation of a 1:1 complex
between iron() and the dihydroxy function of noradrenaline,
J. Chem. Soc., Dalton Trans., 1998, Pages 1315–1319
1315

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HO
HO
OH
Table 1 Typical values of k1obs {[Fe]T = (1.0 Ϫ 5.0) × 10Ϫ4 mol dmϪ3
}
Fe(OH)2+
+
H3N
obs
103[Hϩ]/
103[L]T/
k1
/
k1obs[Hϩ]Ϫ1
/
[L]T[Hϩ]Ϫ2
/
mol dmϪ3
mol dmϪ3
sϪ1
dm3 molϪ1 sϪ1 dm3 molϪ1
Noradrenaline
pH
k′2
2.07
1.20
1.22
1.22
1.24
1.25
1.27
1.27
1.27
1.28
1.35
1.36
1.36
1.52
1.53
1.53
1.55
1.58
1.58
1.64
1.66
2.00
2.28
2.50
3.15
3.21
81.5
77.8
77.8
74.2
72.5
69.2
69.2
69.2
67.6
57.4
5.6
13.80
6.90
10.35
5.00
10.00
10.00
5.00
7.50
7.50
13.80
6.90
10.35
10.00
7.50
10.00
7.50
5.00
10.00
3.50
5.00
5.00
5.00
5.00
5.00
2.38
1.97
2.17
1.72
1.95
1.80
1.61
1.79
1.64
2.07
1.62
1.81
1.73
1.45
1.68
1.44
1.21
1.60
0.72
0.90
0.74
1.00
1.47
4.20
4.43
29.2
k1
1.14
25.3
1.71
27.9
0.91
23.2
O
OH
O
O
OH
k2
1.90
26.9
Fe3+
2.10
26.0
O
H3N
H3N
1.04
23.3
1.57
25.9
Iron (III) Complex
Semiquinone
1.64
24.3
FeIII
(fast)
4.20
36.1
2.19
28.9
OH
3.30
32.3
5.6
HO
O
O
OH
6.75
45.0
kcyc
38.5
37.6
37.6
35.9
33.5
33.5
2.91
2.77
1.25
0.648
0.387
0.084
0.073
5.31
38.6
7.07
44.7
N
HO
H3N
H
5.82
40.1
Leuconoradrenochrome
Quinone
4.46
36.1
FeIII
(high pH)
8.91
47.8
OH
O
N
HO
5.00
Noradrenochrome
Scheme 1 Overall route of oxidation of noradrenaline
was measured immediately after each kinetic run with a WTW
521 pH meter and [Hϩ] was calculated by the empirical relation-
ship9 [Hϩ] = 10Ϫ[(pH Ϫ 0.131)/0.982]. The concentrations of iron()
used were sufficiently low to ensure that any changes in pH
during reaction were negligible.
Kinetic stopped-flow techniques using absorption within
the visible and near-UV region were carried out with a
Bio-sequential SX-17MV (sequential stopped-flow ASVD
spectrophotometer), supplied by Applied Photophysics, Ltd.
(London). The formation of the complex was followed at 714
nm, while the formation and disappearance of the quinone
were monitored at 380 nm. All kinetic runs were performed
with noradrenaline in great excess over iron() in order to
maintain pseudo (first)-order kinetics.
Fig. 1 Variation with pH of the observed rate constants, k1obs, for the
formation of the iron()–dopamine complex ([Fe]T = 2.5 × 10Ϫ4 mol
dmϪ3, [L]T = 5 × 10Ϫ3 mol dmϪ3). Data from Table 1
Results and Discussion
Complex formation in nitrate media
k1
Fe(OH)2ϩ ϩ H2LHϩ
Fe(LH)2ϩ ϩ H3Oϩ
[or Fe(HLH)3ϩ ϩ H2O] (2)
kϪ1
Above pH ca. 2 the rate of formation of the complex formed
between iron() and noradrenaline is accurately first order
in both [Fe]T and [L]T, but at lower pH the rate varies with,
but is not first order in [L]T. This behaviour has been found for
the closely related catecholamines, adrenaline, dopamine and
dopa,5,10 and arises from reversibility of the reaction.
consideration, the total uncomplexed iron() is given by
equation (3), and the observed rate law can be written as in
[Fe]T = [Fe3ϩ] ϩ [Fe(OH)2ϩ
]
(3)
Typical first-order rate constants, k1obs, for complex form-
ation are given in Table 1 and presented graphically in Fig. 1
which shows that the rate passes through a distinct minimum at
pH ca. 2. Bearing in mind that Fe(OH)2ϩ is far more reactive
than Fe3ϩ and has a protonation constant (KFeOH) equal to3 660
dm3 molϪ1 [equation (1)], one can readily explain the acceler-
equation (4), and hence in terms of reaction (2) the rate expres-
sion is given by equation (5). By assuming the equilibrium
condition (6) and because: (i) [Fe(LH)2ϩ
]
eq = ([Fe]T,0 Ϫ [Fe]T,eq
d[coloured complex]/dt = k1obs([Fe]T,0 Ϫ [Fe]T,eq
= k1[Fe(OH)2ϩ][H2LHϩ] Ϫ
)
)
(4)
Fe(OH)2ϩ ϩ Hϩ
Fe3ϩ
;
log KFeOH = 2.82 (1)
(aq)
k
Ϫ1[Fe(LH)2ϩ][Hϩ] (5)
k1/kϪ1 = [Fe(LH)2ϩ]eq[Hϩ]/[Fe(OH)2ϩ]eq[H2LHϩ] (6)
ation with decreasing [Hϩ]. To explain the opposite effect at
lower pH and the fact that the rate of complex formation
becomes less than first-order dependent on the total noradren-
aline concentration, [L]T, it is necessary to take reversibility into
account. Therefore it is proposed that both complexes are
formed according to reaction (2). Over the pH range under
and (ii) noradrenaline is used in great excess giving, since it
is fully protonated at these pH values, [H2LHϩ] ≈ [L]T, (iii)
K
FeOH[Hϩ] ӷ 1 at these low pH values.
1316
J. Chem. Soc., Dalton Trans., 1998, Pages 1315–1319

View Article Online
Complex formation in the presence of chloride
Table 2 Variation of k1obs with [ClϪ] (pH 1.10, [L]T = 0.055 mol dmϪ3
)
At pH values below 2 the presence of chloride ions has a
marked effect on the rate of complex formation. The results in
Table 2 show clearly that the rate constant, k1obs, is proportional
to [ClϪ], and Table 3 reports a series of measurements made at
varying [L]T, [ClϪ] and [Hϩ] values.
When equation (8) is applied to data obtained in chloride
media it is seen that the effect on the reverse reaction, repre-
sented by kϪ1, is directly proportional to [ClϪ], whereas the
effect on the forward reaction, k1, is much less and decreases
with increase in pH.
[ClϪ]/mol dmϪ3
k1obs/sϪ1
0.055
2.87
0.065
3.45
0.075
3.85
0.085
4.32
0.095
4.82
obs
Table 3 Typical values of kCl
[ClϪ]/
102[Hϩ]/
103[L]T/
mol dmϪ3
pH
mol dmϪ3
mol dmϪ3
kClobs/sϪ1
0.0075
1.12
1.12
1.12
1.21
1.21
1.21
9.84
9.84
9.84
7.97
7.97
7.97
6.90
10.35
13.80
6.90
10.35
13.80
3.04
3.21
3.41
2.57
2.80
2.98
These effects can be explained by assuming that the species
FeCl2ϩ is also able to react with H2LHϩ [equation (9)], which is
kCl
FeCl2ϩ ϩ H2LHϩ
FeLH2ϩ ϩ ClϪ ϩ 2Hϩ
(9)
0.025
1.15
1.15
1.15
1.30
1.30
1.30
8.98
8.98
8.98
5.75
5.75
5.75
6.90
13.80
17.30
10.35
13.80
17.30
4.06
4.60
4.89
3.17
3.47
3.69
predominantly reversible only via the non-chloride route (2).
Allowance must also be made for the fact that [Fe]T must now
be written as in equation (10) which reduces to (11) since it is
[Fe]T = [Fe3ϩ] ϩ [FeCl2ϩ] ϩ [Fe(OH)2ϩ
]
(10)
0.0384
1.58
1.59
1.56
1.87
1.87
1.87
5.35
3.27
3.51
1.59
1.59
1.59
6.90
10.35
12.40
6.90
10.35
12.40
2.50
3.18
3.47
2.61
3.51
3.99
[Fe]T = [Fe3ϩ] ϩ [FeCl2ϩ] = [Fe3ϩ](1 ϩ K1Cl[ClϪ]) (11)
possible to neglect the value of [Fe(OH)2ϩ] with respect to
[FeCl2ϩ] and in which K1Cl is the formation constant for FeCl2ϩ
.
Thus, in the presence of chloride, equation (5) must be replaced
by (12). This leads to equation (8) being replaced by (13)† in
d[coloured complex]/dt = k1[Fe(OH)2ϩ][H2LHϩ] Ϫ
k
Ϫ1[Fe(LH)2ϩ][Hϩ] ϩ kCl[FeCl2ϩ][H2LHϩ] (12)
kClobs = (k1 ϩ kClKFeOHK1Cl[ClϪ][Hϩ])[L]T/KFeOH[Hϩ] ϩ
kϪ1Cl[Hϩ] (13)
which kϪ1Cl = kϪ1(1 ϩ K1Cl[ClϪ]). Thus plotting kClobs/[Hϩ] vs.
[L]T/[Hϩ]2 yields kϪ1Cl = kϪ1(1 ϩ K1Cl[ClϪ]) as intercept and a
slope dependent on [Hϩ] and [ClϪ] as observed (above).
Plotting kClobs vs. [L]T for sets of results at constant [Hϩ] and
[ClϪ] yields straight lines with intercepts equal to kϪ1Cl[Hϩ]
and slopes of {(k1 ϩ kClKFeOHK1Cl[ClϪ][Hϩ])/KFeOH[Hϩ]} [see
equation (13)]. From the slopes derived in this way we obtained
a value of kCl = 48 3 dm3 molϪ1 sϪ1 [compare this with the
corresponding value of 43 2 dm3 molϪ1 sϪ1 obtained for the
iron()–dopamine system].
Fig. 2 Plot of k1obs/[Hϩ] vs. [L]T/[Hϩ]2 for values below pH 1.6 (data
from Table 1)
Complex formation in the presence of bromide
Unlike chloride ions, the presence of bromide ions had no effect
on the rate of reaction. Although this could be ascribed to
FeBr2ϩ being non-reactive, the concentration of this species is
not detectable (via speciation effects) and so the lack of reactiv-
ity could equally well be a result of too low a concentration.
Therefore the equilibrium condition (6) reduces to (7). Insert-
[Fe]T,eq = kϪ1KFeOH[Hϩ]2[Fe]T,0/(k1[L]T ϩ kϪ1KFeOH[Hϩ]2) (7)
ing this and the above assumptions into the rate law leads, after
comparison with the observed rate law (4), to equation (8).
Decomposition (electron transfer) step
At constant [Hϩ] and [L]T the rate of decomposition is given by
equation (14), and some typical values of k2 for pH < 2 are
k1obsKFeOH[Hϩ] = k1[L]T ϩ kϪ1KFeOH[Hϩ]2
(8)
obs
Thus a plot of k1obs/[Hϩ] vs. [L]T/[Hϩ]2 should be linear with
intercept corresponding to kϪ1 and a slope of k1/KFeOH. This is
Ϫd[coloured complex]/dt = k2obs[Fe]T
(14)
illustrated in Fig. 2 (Table 1) and, using KFeOH = 660 dm3 molϪ1
yields the results k1 = 2170 20 dm3 molϪ1 sϪ1 and kϪ1 = 21
,
given in Table 4. Plotting 1/k2obs vs. [Hϩ] for the values obtained
at relatively low noradrenaline concentrations (Table 4) yields a
series of straight lines with a common intercept of 70 (Fig. 3),
3 dm3 molϪ1 sϪ1. The ratio k1/kϪ1 thus enables the stability con-
M
K1
stant, K1M, of the Fe(LH)2ϩ complex [Fe3ϩ ϩ LHϪ
H
Fe(LH)2ϩ] to be calculated from the relationship K1M = k1β2
/
† Unfortunately, in ref. 12, the corresponding equation is incorrectly
FeOH
H
k
K
Ϫ1
(where β2 is the microconstant for the protonation
quoted; the factor (1 ϩ K1Cl[ClϪ]) should have been omitted since it had
of the phenolic groups11 of the noradrenaline). A value of log
Cl
been incorporated in kϪ1 and kClobs. The corrected value of kCl for
K1M = 21.2 was obtained.
dopamine is therefore 43 2 dm3 molϪ1 sϪ1
.
J. Chem. Soc., Dalton Trans., 1998, Pages 1315–1319
1317

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obs
Table 4 Typical values of k2
Table 5 Typical rate constants of the formation of noradrenoquinone
(k2Јobs), followed at 380 nm
102[Hϩ]/
103k2
/
103[L]T/
obs
pH
mol dmϪ3
sϪ1
mol dmϪ3
102[Hϩ]/
103[L]T/
103[Fe]T/
103 k2Јobs
/
pH
mol dmϪ3
mol dmϪ3
mol dmϪ3
sϪ1
(a) Results at low noradrenaline concentrations
1.24
1.30
1.39
1.48
1.55
1.66
7.42
6.45
5.22
4.23
3.59
2.77
10.00
10.00
10.00
10.00
10.00
10.00
1.00
1.00
1.00
1.00
1.00
1.00
9.32
9.92
8.99
1.18
1.24
1.37
1.19
1.35
1.64
1.24
1.37
1.66
1.11
1.23
1.43
8.35
5.74
2.91
7.42
5.47
2.77
10.07
7.60
4.76
2.45
3.25
5.02
3.81
5.24
7.08
3.98
4.87
6.62
3.5
3.5
3.5
5.0
5.0
5.0
7.5
7.5
7.5
At relatively higher noradrenaline concentrations (Table 4),
the contribution to the redox reaction of internal electron
transfer within the protonated complex must be taken into
account [equation (19)]. However, it is the total amount of
(b) Results at higher noradrenaline concentrations
1.31
1.46
1.67
1.31
1.46
1.67
1.31
1.46
1.67
6.3
4.5
2.7
6.3
4.5
2.7
6.3
4.5
2.7
1.8
1.6
1.6
2.2
2.1
2.0
3.3
3.1
2.8
10
10
10
15
15
15
25
25
25
Ϫd[Fe]T/dt = k2Ј[Fe(OH)2ϩ][H2LHϩ] ϩ k2[Fe(HLH)3ϩ
]
(19)
complex, i.e. [Fe(LH)2ϩ] ϩ [Fe(HLH)3ϩ], that is being followed,
and this is the coloured indicator for [Fe]T and thus (19)
becomes (20) in which the term in k2Ј is expressed in terms of
Ϫd[Fe]T/dt = {[L]T/(13.2[Hϩ] ϩ 70[L]T) ϩ
k2KMH[Hϩ][L]T/(1 ϩ KMH[Hϩ])}[Fe]T (20)
obs
the experimental value (15) obtained above. Therefore, k2 is
given by equation (21) which enables k2 and KH to be calcu-
M
2k2obs = [L]T/(6.6[Hϩ] ϩ 35[L]T) ϩ
k2KMH[Hϩ][L]T/(1 ϩ KMH[Hϩ]) (21)
lated from the data in Table 4. {Note that the differences
required, namely 2k2obs Ϫ [L]T/(6.6[Hϩ] ϩ 35[L]T), were too
small in the case of [L]T = 0.01 mol dmϪ3 and were therefore not
used.} Values of k2 = 2.6 0.1 sϪ1 and KMH = 34 1 dm3 molϪ1
were obtained. The rate constant, k2, for the rate of decom-
position of the complex is considerably higher than that
obtained for dopamine12 (0.23 sϪ1) and this reflects the con-
siderably greater stability of the dopamine complex against
internal electron transfer followed by decomposition. The
protonation constants, KMH, for the iron() complexes of all
the catecholamines studied are, as would be expected, almost
identical.
obs
Fig. 3 Plot of 1/k2 vs. [Hϩ] for ‘low’ [L]T values (Table 4): 103[L]T =
3.50 (᭿), 5.00 (᭹), 7.50 (᭡) mol dmϪ3
the slopes of which are directly proportional to [L]T. This can
be expressed by equation (15) and can be shown to arise from
k2obs = [L]T/(13.2[Hϩ] ϩ 70[L]T)
(15)
the reaction of Fe(OH)2ϩ with H2LHϩ to form the semiquinone
Formation of quinone
Table 5 contains some typical first-order rate constants (k2Јobs
)
[equation (16)], and since this is also the mode of formation
for quinone formation and it is readily ascertained that k2Јobs
Ϫd[Fe]T/dt = k2Ј[Fe(OH)2ϩ][H2LHϩ]
(16)
obs
equals k2 (i.e. the rate determining step in the formation of
the quinone is the initial electron transfer in the complex). This
implies that no information as to the actual rate of formation
of the quinone from the semiquinone can be ascertained by this
method of studying the reaction; this is the same result as was
found for dopa,10 and also confirms that the subsequent oxid-
ation of the semiquinone is fast, as is to be expected for a
radical–radical reaction.
of the complex (above) this implies an ‘outer-sphere’ redox reac-
tion. This has not been observed for any of the other catechol-
amines with the exception of 6-hydroxydopamine1,8 which
reacts solely by this route (i.e. there is no evidence for complex
formation). Under these conditions of low pH and noting that
complex formation had reached equilibrium we can write, to a
good approximation equation (17), and inserting this result into
Formation of the indole ring
[Fe]T = [Fe3ϩ] ϩ [Fe(HLH)3ϩ] =
The quinones of catecholamines such as noradrenaline spon-
taneously cyclise via an internal Michael addition to form the
UV transparent leuconoradrenochrome (indoline-3,5,6-diol)
(see Scheme 2). The kinetics of this cyclisation reaction for
noradrenaline was followed by monitoring the quinone at 380
nm. This was possible by using iron() as an oxidant up to a
pH of about 3, because the spectral absorption of the quinone
exceeded that of the complex. At higher pH, however, the oxid-
ation was performed using periodate as the oxidant, in order
[Fe3ϩ](β2H[Hϩ] ϩ K MHK1M[L]T)/β2H[Hϩ] (17)
Ϫd[Fe]T/dt = k2Јβ2H[L]T[Fe]T/
KFeOH(β2H[Hϩ] ϩKMHK1M[L]T) (18)
(16) yields (18). Noting also that the semiquinone formed reacts
rapidly with another iron() to form the quinone, comparison
of equation (18) with (14) yields (19). Using the experimental
result equation (15) gives a value of k2Ј = 100 2 dm3 molϪ1 sϪ1
.
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J. Chem. Soc., Dalton Trans., 1998, Pages 1315–1319

View Article Online
must imply that protonation of the quinone function takes place
Table 6 Typical values for the observed rate constant, k3obs, for
indole formation (ring-closure reaction) following oxidation of the
noradrenaline to the quinone
at low pH. We further assume that deprotonation at the amino
site is a requirement for cyclisation, and because the proton-
ation constant of this functional group is very high [log
KNH = log(ka/kϪa) = 9.53] this (deprotonation) step is relatively
slow and must also be taken into account in formulating the
reaction scheme. These ideas are summarised in Scheme 2.
The experimental results can be interpreted on the basis of
this scheme and the associated postulates as follows. Under
reaction conditions [Q] (or [HQϩ]) will reach a steady state, as
shown in equations (24) and (25), but the total quinone concen-
obs
pH
Oxidant
log k3
Ϫ3.55
Ϫ3.15
Ϫ3.19
Ϫ3.21
Ϫ2.80
0.93
1.58
1.71
1.73
2.12
Iron()
3.74
4.90
6.40
7.90
8.52
9.60
Periodate
Ϫ2.20
Ϫ1.31
0.10
1.22
1.50
d[Q]/dt = 0 = kϪa[QHϩ] Ϫ ka[Q][Hϩ] Ϫ kcyc[Q] (24)
[Q] = [QHϩ]/(KNH[Hϩ] ϩ kcyc/kϪa
)
(25)
1.58
tration, [Q]T, as given by equation (26), and the combination
[Q]T = [QHϩ] ϩ [HQH2ϩ] = [QHϩ](1 ϩ KQH[Hϩ]) (26)
O
O
OH
O
O
OH
H
KQ
H+
H3N
QH+
H3N
of equations (23), (25) and (26) taken in comparison with (22)
leads to equation (27), in which KNH = ka/kϪa is the protonation
HQH2+
k3obs = (kcyc ϩ kcycHKQH[Hϩ])/
ka k–a
ka k–a
{(KNH[Hϩ] ϩ kcyc/kϪa)(1 ϩ KQH[Hϩ])} (27)
O
O
OH
O
O
OH
H
H
microconstant for the amino group. The value of KN is
KQ
known11 (log KNH = 9.53) and kϪa was obtained from the limit-
H+
ing value of k3 at high pH [i.e. where [Hϩ]→0, see equation
obs
H2N
Q
H2N
HQ+
(27)] and has the value of 30.0 sϪ1. Thus the rate constants
H
for the cyclisation reaction and the protonation constant KQ
kH
kcyc
were readily obtained from equation (27): kcyc = 1400 20 sϪ1
(for quinone), kcycH = (2.0 0.1) × 105 sϪ1 (for protonated
quinone) and log KQH = 1.55.
cyc
OH
HO
N
H
HO
Acknowledgements
Thanks are due to the Fonds zur Förderung der Wissen-
schaftlichen Forschung in Österreich (Project 11218-CHE), to
the Austrian Ministry of Science Education and Transport and
the Jubiläumsfonds der Österriechen 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.
Leuconoradrenochrome
Scheme 2 Details of ring-closure reaction
References
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Fig. 4 Observed rate of cyclisation of noradrenoquinone, log k3obs, vs.
pH (experimental points with the theoretical curve)
to avoid the interference of the iron() complexes which absorb
at these higher pH values.
The rate of disappearance of the quinone follows the rate law
(22) and typical results are summarised in Table 6 and illus-
Ϫd[Q]T/dt = k3obs[Q]T
(22)
11 A. Gergely, T. Kiss, G. Deák and I. Sóvágó, Inorg. Chim. Acta, 1981,
56, 35.
12 U. El-Ayaan, E. Herlinger, R. F. Jameson and W. Linert, J. Chem.
Soc., Dalton Trans., 1997, 2813.
trated in Fig. 4. The results strongly suggest that two quinone
species are involved, one being protonated [equation (23)]. This
Ϫd[Q]T/dt = kcyc[Q] ϩ kcycH[HQϩ] =
(kcyc ϩ kcycHKQH[Hϩ])[Q] (23)
Received 1st December 1997; Paper 7/08639C
J. Chem. Soc., Dalton Trans., 1998, Pages 1315–1319
1319