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

Abstract

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⁺ (K ₁^Cl) was found to be 35, i.e. log K ₁^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 K ₁^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, k₂′ = 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).