Nitrogen Oxidation in Ferrihaemoglobin Formation

Abstract

1. N-Hydroxyarylamines, N-hydroxy-N-alkylarylamines, and N,N-dialkyl-arylamine-N-oxides form ferrihaemoglobin in the presence of oxygen; none of the compounds oxidizes ferrohaemoglobin directly.

2. The hydroxylamines produce ferrihaemoglobin in a ‘coupled oxidation’ of the hydroxylamine of ferrohaemoglobin. This begins with the oxidation of the hydroxylamine by oxyhaemoglobin and, in a series of reactions, transforms oxyhaemoglobin as well as deoxyhaemoglobin into ferrihaemoglobin and phenylhydroxylamine into nitrosobenzene.

3. In red cells nitrosobenzene is reduced to phenylhydroxylamine by NADPH-specific diaphorases. Thus a cycle is started which with each mole of phenylhydroxylamine or nitrosobenzene entering the red cell transforms many equivalents of ferrohaemoglobin to ferrihaemoglobin.

4. The formation of ferrihaemoglobin by N,N-dimethylaniline-N-oxide shows an autocatalytic increase in rate, ferrihaemoglobin being the catalyst. In addition to inactive products like formaldehyde, N-methylaniline, and N,N-dimethylaniline, the reaction between N,N-dimethylaniline-N-oxide and ferrihaemoglobin yields three aminophenols, namely 4-dimethylaminophenol, 2-dimethylaminophenol, and a purple dye. Aminophenols act as catalysts of the transfer of electrons from ferrohaemoglobin to oxygen.