Partition coefficients of the iron (III) complexes of pyridoxal isonicotinoyl hydrazone and its analogs and the correlation to iron chelation efficacy. Correction of some reported partition coefficients

Pyridoxal isonicotinoyl hydrazone (PIH), salicylaldehyde benzoyl hydrazone (SBH), and their analogs chelate iron(III) and show promise as orally effective drugs for treating diseases of iron overload. Their biological activity is related to their lipophilicity, as measured by their partition coefficients P between n-octanol and water. However, the method of calculating log P described in an article in this journal (Edward et al, 1995; BioMetals, 8, 209-217) is faulty for compounds such as PM, SBH and their analogs which contain adjacent hydrophilic groups. Consequently, the calculations reported in the article, based on erroneous log P values of the chelating molecules, give erroneous log P values of the iron(III) complexes, The chelators most effective in mobilizing Fe-59 from reticulocytes have log P approximate to 2.8, not log P approximate to 0 and the iron(III) complexes of the most effective chelators have log P approximate to 3.1, not log P approximate to 0.