Chemical evaluation of compounds as nitric oxide or peroxynitrite donors using the reactions with serotonin

Abstract

The aim of this work was to assess the capacities of some ^·NO-donors to release ^·NO, and consequently NOx in aerobic medium, or to give peroxynitrite. The method was based on the differential reactivity of serotonin (5-HT) with either NO_x or peroxynitrite, leading in phosphate-buffered solutions to 4-nitroso- and 4-nitro-5-HT formation, respectively. Yields and formation rates of 5-HT derivatives with ^·NO-donor were compared to those obtained with authentic ^·NO or peroxynitrite in similar conditions. Aside from the capacity of diazenium diolates (SPER/NO and DEA/NO) to release ^·NO spontaneously, converting 5-HT exclusively to 4-nitroso-5-HT, all other ^·NO donors must undergo redox reactions to produce ^·NO. S-nitrosoglutathione (GSNO) and sodium nitroprus-side (SNP) modified 5-HT only in the presence of Cu²⁺, GSNO yielding 6 times more 4-nitroso-5-HT than SNP. Furthermore, in the presence of Cu⁺, the yield of ^·NO-release from GSNO was 45%. The molsidomine metabolite (SIN-1), which was presumed to release both ^·NO and O2/·- at pH 7.4, reacted with 5-HT differently, depending on the presence of reductant or oxidant. Under aerobic conditions, SIN-1 acted predominantly as a 5-HT oxidant and also as a poor ^·NO and peroxynitrite donor (15% yield of ^·NO-release and 14 % yield of peroxynitrite formation). The strong oxidant Cu²⁺, even in the presence of air oxygen, accelerated oxidation and increased ^·NO release from SIN-1 up to 86%. Only a small part of SIN-1 gave simultaneously ^·NO and O2/·- able to link together to give peroxynitrite, but other oxidants could enhance ^·NO release from SIN-1.

Keywords:

• NO-donor
• peroxynitrite
• thionitrite
• nitroprus-side
• NONOate
• morpholinosydnonymine
• nitrosation
• nitration
• hydroxytryptamine