Biomimetic Electrochemistry: A Study of the Electrochemical and Peroxidase‐Mediated Oxidation of 5‐Hydroxytryptophan

Abstract

The electrochemically-driven and peroxidase-mediated oxidations of 5-hydroxytryptophan (5-HTPP) in acidic solution have been studied. Both oxidation processes yield a complex mixture of identical products. Under a limited set of experimental conditions, the first voltammetric oxidation peak of 5-HTPP at a pyrolytic graphite electrode exhibits linear diffusion control. Based upon the peak characteristics it may be implied that the initial step in the electro-oxidation is a reversible one-electron abstraction to give a radical cation that deprotonates to a neutral radical, 5-HTPP'. Attack by 5-HTPP on this radical leads to three sets of diastereomeric dimers. 5-HTPP" can also be further oxidized (le) to a quinone imine that is attacked by water and then oxidized to give tryptophan-4,5-dione. Additional chemical/electrochemical reactions generate other products including one fully characterized trimer. The electrochemical process appears to exactly mimic the enzymatic reaction.There is considerable interest in understanding the oxidation chemistry and biochemistry of various indoleamines found naturally in the central nervous system because such chemistry might provide some insights into the etiology of certain mental illnesses (1, 2). We have recently initiated a program to study the electrochemical oxidation of such indoleamines with the expectation that the information obtained might provide a basis for understanding the enzyme-mediated oxidations of these compounds. Recently, we reported preliminary results concerning the electrochemical oxidation of 5-hydroxytryptophan (5-HTPP) in aqueous acidic solution at a pyrolytic graphite electrode (PGE) (2). Some of the products were identified and included several dimeric compounds and, as a result, it seemed likely that radical intermediates might be involved. However, because of strong adsorption of 5-HTPP at the PGE, voltammetric techniques could not be employed to probe mechanistic aspects of the electrochemically driven reaction. Furthermore, not all major oxidation products were isolated and identified.In this report a more complete description of the products and mechanisms of the electrochemical oxidation of 5-HTPP is presented. In addition, the electrochemically driven and peroxidase-mediated oxidations of 5-HTPP are compared.

Applications of electrochemistry in studies of the oxidation chemistry of central nervous system indoles

“…Peroxidase derived from horseradish and mammalian peroxidase-H202 systems has been reported to oxidize biogenic indoles although reaction products were not identified.106 It has been speculated106 that peroxidative 5-hydroxyindolamine catabolism, for example, might play a prominent role in situations where the enzyme monoamine oxidase is inhibited as well as in cancerous tissue, which often possesses high levels of peroxidase.107 A comparison of the peroxidase-H202 and electrochemical oxidation of 5-HTPP has been carried out. 63,104 Chromatograms of the product solutions formed as a result of these oxidations are shown in Figure 10. Clearly, the product profiles resulting from both types of oxidation reactions are identical, suggesting that the chemical mechanisms leading to these products are the same.…”

5-Hydroxytryptophan as a Precursor of a Catalyst for the Oxidation of NADH

“…It has, however, been mentioned when the oxidation takes place in acid solutions. 35,36 In this case, the authors suggest that C is responsible for the redox activity of process III. Compound C is a proposed intermediate of a dimer with a quinoline structure.…”

“…To our knowledge, there are no reports concerning the appearance of process III during the oxidation of this compound in neutral solutions. It has, however, been mentioned when the oxidation takes place in acid solutions. , In this case, the authors suggest that C is responsible for the redox activity of process III. Compound C is a proposed intermediate of a dimer with a quinoline structure.…”

“…It is well known that the electrooxidation of 5-hydroxytryptophan (5-HTPP) gives rise to a tryptophan-4,5-dione − product that strongly adsorbs to carbon electrodes. In principle, this compound, with an o -quinone structure, is expected to act as a catalyst for the oxidation of NADH.…”