Redox and structural aspects on iron inositol 1,2,3-trisphosphate interaction: An experimental and computational approach

Among small cellular molecules, certain inositol phosphates (InsPs) excel at complexing Fe3+ in a safe manner in vitro. In particular Ins(1,2,3)P3 is probably an important chelator of iron cations not strongly bound to proteins, which avoids iron redox cycling and the associated production of free radicals. In this work we report the first thermodynamic data of the Fe3+/Fe2+ redox potential in the presence of Ins(1,2,3)P3 which demonstrate the capability of this ligand to inhibit iron(III) reduction in the intracellular media. The Fe3+–Ins(1,2,3)P3 speciation was also studied by 31P NMR measurements, focusing on the structure of the complexes. The work is completed by theoretical calculations which lead us to predict the geometries of the species at different pH values and their relative stabilities. The influence of the ring conformation in the Fe3+ complexed forms is also discussed.