Formation of Oxygen Radicals in Solutions of Different 7,8‐Dihydropterins: Quantitative Structure‐Activity Relationships

Under certain conditions, 7,8‐dihydroneopterin in aqueous solution promotes hydroxyl‐radical formation. Thus, we investigated the stimulation of hydroxyl‐radical formation by ten different 7,8‐dihydropterins (=2‐amino‐7,8‐dihydropteridin‐4(1H)‐one), i.e., 6‐(1′‐hydroxy) derivatives 1 and 2 , methyl derivatives 3 – 7 , and 6‐(1′‐oxo) derivatives 8 – 10 . All but the 6‐(1′‐oxo) derivatives produced hydroxyl radicals, as measured by the amount of salicylic acid hydroxylation products. This amount was dependent on the stability of the dihydropterin used. In the presence of chelated iron ions, hydroxylation was increased in every case; even 6‐(1′‐oxo) derivatives showed a low hydroxylation of salicylic acid. The degree of increase, however, strongly depended on the side chain of the dihydropterin. The 7,8‐dihydroneopterin ( 2 ) was investigated in more detail. Iron ions influenced both, the stability of 2 and hydroxyl‐radical formation. While iron ions determined the kinetics of the reaction, the amount of 2 was responsible for the amount of hydroxyl radicals formed. Our data establish that promotion of hydroxyl‐radical formation by 7,8‐dihydropterins depends on the oxidizability of the dihydropterins and on their iron‐chelating properties.