DALTON FULL PAPER J. Chem. Soc. Dalton Trans. 1998 Pages 1315–1319 1315 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 H2LH1 (in which the phenolic protons are written on the left of L)] reacts with iron(III) [in the form of Fe(OH)21] 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)21 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 eVect on the rate of complex formation because the species FeCl21 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 FeCl21 (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)21 1 H2LH1] k1 = 2170 ± 20 dm3 mol21 s21 and k21 = 21 ± 2 dm3 mol21 s21 from which the stability constant of the Fe(LH)21 complex has been calculated (log K1 M = 21.2) (ii) rate of formation of the complex via FeCl21 1 H2LH1 kCl = 48 ± 3 dm3 mol21 s21 (iii) rate of decomposition of the complex Fe(HLH)31 k2 = 2.6 ± 0.1 s21 [protonation constant for Fe(LH)21 KM H = 34 ± 1 dm3 mol21] (iv) rate of outer-sphere redox reaction k29 = 100 ± 2 dm3 mol21 s21 (v) rate of indole formation (ring-closure reaction) kcyc = 1400 ± 20 s21 (for quinone) and kcyc H = (2.0 ± 0.1) × 105 s21 (for protonated quinone).All measurements were carried out at 25.0 8C in solutions of ionic strength 0.10 mol dm23 (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 attention because unlike most of the catecholamine family no complex with iron(III) can be detected but it reacts directly 1 with iron(III) to form iron(II) and a semiquinone (i.e.by an ‘outersphere’ 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(III) and the redox reaction then proceeds via internal electron transfer within the complex. This diVerence 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(III) via both reactions (i.e. by parallel ‘inner-sphere’ and ‘outer-sphere’ electrontransfer 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 diVerent conditions under which they were obtained (at high pH in glycol) makes their relevance uncertain. When iron(III) 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(II). In the present case this green colour is due to the formation of a 1 1 complex between iron(III) and the dihydroxy function of noradrenaline 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 complex but reacts directly with the iron(III) 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 yellowgreen noradrenoquinone [formed by rapid reaction of the semiquinone with another iron(III)]. This subsequently cyclises by an intramolecular Michael condensation to form the UV transparent 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 converted to nitrate by use of an ion-exchange column) and of iron(III) (as nitrate nonahydrate Merck p.a.) that contained a calculated amount of HNO3 and suYcient KNO3 to maintain the final ionic strength at 0.100 mol dm23. Experiments were also carried out with solutions containing KCl in order to investigate the eVect of chloride ions on the reaction. The pH 1316 J. Chem. Soc. Dalton Trans. 1998 Pages 1315–1319 was measured immediately after each kinetic run with a WTW 521 pH meter and [H1] was calculated by the empirical relationship 9 [H1] = 102[(pH 2 0.131)/0.982].The concentrations of iron(III) used were suYciently 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(III) in order to maintain pseudo (first)-order kinetics. Results and Discussion Complex formation in nitrate media Above pH ca.2 the rate of formation of the complex formed between iron(III) 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. Typical first-order rate constants k1 obs for complex formation 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)21 is far more reactive than Fe31 and has a protonation constant (KFeOH) equal to 3 660 dm3 mol21 [equation (1)] one can readily explain the acceler- Fe(OH)21 1 H1 Fe31 (aq); log KF eOH = 2.82 (1) ation with decreasing [H1].To explain the opposite eVect at lower pH and the fact that the rate of complex formation becomes less than first-order dependent on the total noradrenaline 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 Scheme 1 Overall route of oxidation of noradrenaline HO HO H3N OH O O H3N OH O O H3N OH O O H3N OH Fe3+ Fe(OH)2+ + Noradrenaline Iron (III) Complex Semiquinone Quinone k1 k2 k¢2 FeIII (fast) HO HO Leuconoradrenochrome NH OH kcyc O HO Noradrenochrome N OH FeIII (high pH) Fe(OH)21 1 H2LH1 k1 k21 Fe(LH)21 1 H3O1 [or Fe(HLH)31 1 H2O] (2) consideration the total uncomplexed iron(III) is given by equation (3) and the observed rate law can be written as in [Fe]T = [Fe31] 1 [Fe(OH)21] (3) equation (4) and hence in terms of reaction (2) the rate expression is given by equation (5).By assuming the equilibrium condition (6) and because (i) [Fe(LH)21]eq = ([Fe]T,0 2 [Fe]T,eq) d[coloured complex]/dt = k1 obs([Fe]T,0 2 [Fe]T,eq) (4) = k1[Fe(OH)21][H2LH1] 2 k21[Fe(LH)21][H1] (5) k1/k21 = [Fe(LH)21]eq[H1]/[Fe(OH)21]eq[H2LH1] (6) and (ii) noradrenaline is used in great excess giving since it is fully protonated at these pH values [H2LH1] ª [L]T (iii) KFeOH[H1] @ 1 at these low pH values. Fig. 1 Variation with pH of the observed rate constants k1 obs for the formation of the iron(III)–dopamine complex ([Fe]T = 2.5 × 1024 mol dm23 [L]T = 5 × 1023 mol dm23). Data from Table 1 Table 1 Typical values of k1 obs {[Fe]T = (1.0 2 5.0) × 1024 mol dm23} pH 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 3.21 103[H1]/ mol dm23 81.5 77.8 77.8 74.2 72.5 69.2 69.2 69.2 67.6 57.4 5.6 5.6 38.5 37.6 37.6 35.9 33.5 33.5 2.91 2.77 1.25 0.648 0.387 0.084 0.073 103[L]T/ mol dm23 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 5.00 k1 obs/ s21 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 k1 obs[H1]21/ dm3 mol21 s21 29.2 25.3 27.9 23.2 26.9 26.0 23.3 25.9 24.3 36.1 28.9 32.3 45.0 38.6 44.7 40.1 36.1 47.8 [L]T[H1]22/ dm3 mol21 2.07 1.14 1.71 0.91 1.90 2.10 1.04 1.57 1.64 4.20 2.19 3.30 6.75 5.31 7.07 5.82 4.46 8.91 J.Chem. Soc. Dalton Trans. 1998 Pages 1315–1319 1317 Therefore the equilibrium condition (6) reduces to (7). Insert- [Fe]T,eq = k21KFeOH[H1]2[Fe]T,0/(k1[L]T 1 k21KFeOH[H1]2) (7) ing this and the above assumptions into the rate law leads after comparison with the observed rate law (4) to equation (8). k1 obsKFeOH[H1] = k1[L]T 1 k21KFeOH[H1]2 (8) Thus a plot of k1 obs/[H1] vs. [L]T/[H1]2 should be linear with intercept corresponding to k21 and a slope of k1/KFeOH. This is illustrated in Fig. 2 (Table 1) and using KFeOH = 660 dm3 mol21 yields the results k1 = 2170 ± 20 dm3 mol21 s21 and k21 = 21 ± 3 dm3 mol21 s21. The ratio k1/k21 thus enables the stability constant K1 M of the Fe(LH)21 complex [Fe31 1 LH2 K1 M Fe(LH)21] to be calculated from the relationship K1 M = k1b2 H/ k21KFeOH (where b2 H is the microconstant for the protonation of the phenolic groups11 of the noradrenaline).A value of log K1 M = 21.2 was obtained. Fig. 2 Plot of k1 obs/[H1] vs. [L]T/[H1]2 for values below pH 1.6 (data from Table 1) Table 2 Variation of k1 obs with [Cl2] (pH 1.10 [L]T = 0.055 mol dm23) [Cl2]/mol dm23 k1 obs/s21 0.055 2.87 0.065 3.45 0.075 3.85 0.085 4.32 0.095 4.82 Table 3 Typical values of kCl obs [Cl2]/ mol dm23 0.0075 0.025 0.0384 pH 1.12 1.12 1.12 1.21 1.21 1.21 1.15 1.15 1.15 1.30 1.30 1.30 1.58 1.59 1.56 1.87 1.87 1.87 102[H1]/ mol dm23 9.84 9.84 9.84 7.97 7.97 7.97 8.98 8.98 8.98 5.75 5.75 5.75 5.35 3.27 3.51 1.59 1.59 1.59 103[L]T/ mol dm23 6.90 10.35 13.80 6.90 10.35 13.80 6.90 13.80 17.30 10.35 13.80 17.30 6.90 10.35 12.40 6.90 10.35 12.40 kCl obs/s21 3.04 3.21 3.41 2.57 2.80 2.98 4.06 4.60 4.89 3.17 3.47 3.69 2.50 3.18 3.47 2.61 3.51 3.99 Complex formation in the presence of chloride At pH values below 2 the presence of chloride ions has a marked eVect on the rate of complex formation.The results in Table 2 show clearly that the rate constant k1 obs is proportional to [Cl2] and Table 3 reports a series of measurements made at varying [L]T [Cl2] and [H1] values. When equation (8) is applied to data obtained in chloride media it is seen that the eVect on the reverse reaction represented by k21 is directly proportional to [Cl2] whereas the eVect on the forward reaction k1 is much less and decreases with increase in pH. These eVects can be explained by assuming that the species FeCl21 is also able to react with H2LH1 [equation (9)] which is FeCl21 1 H2LH1 kCl FeLH21 1 Cl2 1 2H1 (9) 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 = [Fe31] 1 [FeCl21] 1 [Fe(OH)21] (10) [Fe]T = [Fe31] 1 [FeCl21] = [Fe31](1 1 K1 Cl[Cl2]) (11) possible to neglect the value of [Fe(OH)21] with respect to [FeCl21] and in which K1 Cl is the formation constant for FeCl21. 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)21][H2LH1] 2 k21[Fe(LH)21][H1] 1 kCl[FeCl21][H2LH1] (12) kCl obs = (k1 1 kClKFeOHK1 Cl[Cl2][H1])[L]T/KFeOH[H1] 1 k21 Cl[H1] (13) which k21 Cl = k21(1 1 K1 Cl[Cl2]).Thus plotting kCl obs/[H1] vs. [L]T/[H1]2 yields k21 Cl = k21(1 1 K1 Cl[Cl2]) as intercept and a slope dependent on [H1] and [Cl2] as observed (above). Plotting kCl obs vs. [L]T for sets of results at constant [H1] and [Cl2] yields straight lines with intercepts equal to k21 Cl[H1] and slopes of {(k1 1 kClKFeOHK1 Cl[Cl2][H1])/KFeOH[H1]} [see equation (13)]. From the slopes derived in this way we obtained a value of kCl = 48 ± 3 dm3 mol21 s21 [compare this with the corresponding value of 43 ± 2 dm3 mol21 s21 obtained for the iron(III)–dopamine system]. Complex formation in the presence of bromide Unlike chloride ions the presence of bromide ions had no eVect on the rate of reaction. Although this could be ascribed to FeBr21 being non-reactive the concentration of this species is not detectable (via speciation eVects) and so the lack of reactivity could equally well be a result of too low a concentration.Decomposition (electron transfer) step At constant [H1] and [L]T the rate of decomposition is given by equation (14) and some typical values of k2 obs for pH < 2 are 2d[coloured complex]/dt = k2 obs[Fe]T (14) given in Table 4. Plotting 1/k2 obs vs. [H1] 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) † Unfortunately in ref. 12 the corresponding equation is incorrectly quoted; the factor (1 1 K1 Cl[Cl2]) should have been omitted since it had been incorporated in k21 Cl and kCl obs. The corrected value of kCl for dopamine is therefore 43 ± 2 dm3 mol21 s21.1318 J. Chem. Soc. Dalton Trans. 1998 Pages 1315–1319 the slopes of which are directly proportional to [L]T. This can be expressed by equation (15) and can be shown to arise from k2 obs = [L]T/(13.2[H1] 1 70[L]T) (15) the reaction of Fe(OH)21 with H2LH1 to form the semiquinone [equation (16)] and since this is also the mode of formation 2d[Fe]T/dt = k29[Fe(OH)21][H2LH1] (16) of the complex (above) this implies an ‘outer-sphere’ redox reaction. This has not been observed for any of the other catecholamines 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 [Fe]T = [Fe31] 1 [Fe(HLH)31] = [Fe31](b2 H[H1] 1 KM HK1 M[L]T)/b2 H[H1] (17) 2d[Fe]T/dt = k29b2 H[L]T[Fe]T/ KFeOH(b2 H[H1] 1KM HK1 M[L]T) (18) (16) yields (18).Noting also that the semiquinone formed reacts rapidly with another iron(III) to form the quinone comparison of equation (18) with (14) yields (19). Using the experimental result equation (15) gives a value of k29 = 100 ± 2 dm3 mol21 s21. Fig. 3 Plot of 1/k2 obs vs. [H1] for ‘low’ [L]T values (Table 4) 103[L]T = 3.50 (j) 5.00 (d) 7.50 (m) mol dm23 Table 4 Typical values of k2 obs pH 102[H1]/ mol dm23 103k2 obs/ s21 103[L]T/ mol dm23 (a) Results at low noradrenaline concentrations 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 (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 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 2d[Fe]T/dt = k29[Fe(OH)21][H2LH1] 1 k2[Fe(HLH)31] (19) complex i.e. [Fe(LH)21] 1 [Fe(HLH)31] that is being followed and this is the coloured indicator for [Fe]T and thus (19) becomes (20) in which the term in k29 is expressed in terms of 2d[Fe]T/dt = {[L]T/(13.2[H1] 1 70[L]T) 1 k2KM H[H1][L]T/(1 1 KM H[H1])}[Fe]T (20) the experimental value (15) obtained above.Therefore k2 obs is given by equation (21) which enables k2 and KH M to be calcu- 2k2 obs = [L]T/(6.6[H1] 1 35[L]T) 1 k2KM H[H1][L]T/(1 1 KM H[H1]) (21) lated from the data in Table 4. {Note that the diVerences required namely 2k2 obs 2 [L]T/(6.6[H1] 1 35[L]T) were too small in the case of [L]T = 0.01 mol dm23 and were therefore not used.} Values of k2 = 2.6 ± 0.1 s21 and KM H = 34 ± 1 dm3 mol21 were obtained. The rate constant k2 for the rate of decomposition of the complex is considerably higher than that obtained for dopamine12 (0.23 s21) and this reflects the considerably greater stability of the dopamine complex against internal electron transfer followed by decomposition. The protonation constants KM H for the iron(III) complexes of all the catecholamines studied are as would be expected almost identical.Formation of quinone Table 5 contains some typical first-order rate constants (k29obs) for quinone formation and it is readily ascertained that k29obs equals k2 obs (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 oxidation of the semiquinone is fast as is to be expected for a radical–radical reaction. Formation of the indole ring The quinones of catecholamines such as noradrenaline spontaneously 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(III) 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 oxidation was performed using periodate as the oxidant in order Table 5 Typical rate constants of the formation of noradrenoquinone (k29obs) followed at 380 nm pH 1.24 1.30 1.39 1.48 1.55 1.66 102[H1]/ mol dm23 7.42 6.45 5.22 4.23 3.59 2.77 103[L]T/ mol dm23 10.00 10.00 10.00 10.00 10.00 10.00 103[Fe]T/ mol dm23 1.00 1.00 1.00 1.00 1.00 1.00 103 k29obs/ s21 9.32 9.92 8.99 1.18 1.24 1.37 J.Chem. Soc. Dalton Trans. 1998 Pages 1315–1319 1319 to avoid the interference of the iron(III) 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- 2d[Q]T/dt = k3 obs[Q]T (22) trated in Fig. 4. The results strongly suggest that two quinone species are involved one being protonated [equation (23)]. This 2d[Q]T/dt = kcyc[Q] 1 kcyc H[HQ1] = (kcyc 1 kcyc HKQ H[H1])[Q] (23) Scheme 2 Details of ring-closure reaction O O H3N OH O O H3N OH H+ HO HO N OH O O H2N OH O O H2N OH H+ H HQH2+ HQ+ QH+ Q Leuconoradrenochrome k–a ka KQ H KQ H k–a ka kH cyc kcyc Fig. 4 Observed rate of cyclisation of noradrenoquinone log k3 obs vs.pH (experimental points with the theoretical curve) Table 6 Typical values for the observed rate constant k3 obs for indole formation (ring-closure reaction) following oxidation of the noradrenaline to the quinone pH 0.93 1.58 1.71 1.73 2.12 3.74 4.90 6.40 7.90 8.52 9.60 Oxidant Iron(III) Periodate log k3 obs 23.55 23.15 23.19 23.21 22.80 22.20 21.31 0.10 1.22 1.50 1.58 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 constant of this functional group is very high [log KN H = log(ka/k2a) = 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 [HQ1]) will reach a steady state as shown in equations (24) and (25) but the total quinone concend[ Q]/dt = 0 = k2a[QH1] 2 ka[Q][H1] 2 kcyc[Q] (24) [Q] = [QH1]/(KN H[H1] 1 kcyc/k2a) (25) tration [Q]T as given by equation (26) and the combination [Q]T = [QH1] 1 [HQH21] = [QH1](1 1 KQ H[H1]) (26) of equations (23) (25) and (26) taken in comparison with (22) leads to equation (27) in which KN H = ka/k2a is the protonation k3 obs = (kcyc 1 kcyc HKQ H[H1])/ {(KN H[H1] 1 kcyc/k2a)(1 1 KQ H[H1])} (27) microconstant for the amino group. The value of KN H is known11 (log KN H = 9.53) and k2a was obtained from the limiting value of k3 obs at high pH [i.e.where [H1]Æ0 see equation (27)] and has the value of 30.0 s21. Thus the rate constants for the cyclisation reaction and the protonation constant KQ H were readily obtained from equation (27) kcyc = 1400 ± 20 s21 (for quinone) kcyc H = (2.0 ± 0.1) × 105 s21 (for protonated quinone) and log KQ H = 1.55. Acknowledgements Thanks are due to the Fonds zur Förderung der Wissenschaftlichen 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.References 1 W. Linert E. Herlinger R. F. Jameson E. Kienzl K. Jellinger and M. B. H. Youdim Biochim. Biophys. Acta 1996 1316 160. 2 H. P. Monterio and C. C. Winterbourn Biochem. Pharmacol. 1989 38 4177. 3 R. F. Jameson W. Linert A. Tschinkowitz and V. Gutmann J. Chem. Soc. Dalton Trans. 1988 943. 4 E. Herlinger R. F. Jameson and W. Linert J. Chem. Soc. Perkin Trans. 2 1995 259. 5 W. Linert E. Herlinger and R. F. Jameson J. Chem. Soc. Perkin Trans. 2 1993 2435. 6 S. Steenken and P. Neta J. Phys. Chem. 1982 86 3661. 7 G. Schwarzenbach and A. Willi Helv. Chim. Acta 1951 34 528. 8 G. N. L. Jameson and W. Linert unpublished work. 9 J. E. Gorton Ph.D. Thesis University of St. Andrews 1966. 10 W. Linert R. F. Jameson and E. Herlinger Inorg. Chim. Acta 1991 187 239. 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. Received 1st December 1997; Paper 7/08639C