Interactions of Salicyluric Acid with Metal Ions and Ascorbic Acid: Possible Biological and Toxicity Implications in Aspirin Use.

Abstract

Aspirin is one of the most widely used pharmaceuticals, yet its long-term use is associated with some side effects, including iron-deficiency anemia, which has been mainly linked to the iron-chelating properties of its major metabolite, salicyluric acid (SUA). In this study, the chelating and redox properties of SUA in the presence of iron (Fe³⁺), copper (Cu²⁺), and aluminum (Al³⁺), under neutral pH conditions were investigated using UV-Vis spectrophotometry, Job plot analysis, and ¹H NMR spectroscopy. The stability constants determined for SUA complexes with Cu²⁺ and Al³⁺ were K = 9.9 × 10⁶ and 1.40 × 10⁴ M^-1, respectively, classifying SUA as a moderate-affinity chelator. No detectable complexes of SUA with Fe²⁺ or Cu⁺ were observed, indicating selectivity of SUA for higher oxidation states. Competition experiments with the chelating drug deferiprone (L1) confirmed the quantitative displacement of SUA from metal coordination spheres. In a Fenton-initiated lipid peroxidation model using linoleic acid micelles, SUA-copper and iron metal complexes accelerated lipid oxidation, demonstrating pro-oxidant activity. However, the combination of SUA and vitamin C resulted in a net decrease in the lipid peroxidation rate compared to the system containing SUA alone, suggesting a complex interplay between chelation and redox modulation.