Interactions between iron(III)-hydroxide polymaltose complex and commonly used drugs / simulations and in vitro studies.

Under physiological conditions, ferric ions are essentially insoluble because of the formation of polynuclear hydroxo-bridged complexes. Ferrous ions are more soluble but may produce hydroxyl radicals on reaction with hydrogen peroxide. Chelation of ferric and ferrous ions with organic ligands may prevent these undesirable reactions. Alternatively, iron(III)-hydroxide/oxide can be stabilized and solubilized by tight interactions with carbohydrates. The data presented in this work show that, because of its physicochemical properties, the iron(III)-hydroxide polymaltose complex (IPC, Maltofer) does not interact with the active ingredients of commonly used drugs such as acetylsalicylic acid (CAS 50-78-2), tetracycline hydrochloride (CAS 64-75-5), calcium hydrogen-phosphate (CAS 7757-93-9), methyl-L-dopa sesquihydrate (CAS 41372-08-1), and magnesium-L-aspartate hydrochloride (CAS 28184-71-6). In contrast, as confirmed by calculations using thermodynamic parameters, FeCl3 x 6H2O (CAS 10025-77-1) can form different types of complexes with these substances. Moreover, the data show that under aerobic conditions high concentrations of ascorbic acid (CAS 50-81-7) can lead to mobilization of iron from IPC and, thus, support the observation that orange juice slightly increases the uptake of iron from IPC.

Analysis of the contribution of the globin and reductase domains to the ligand-binding properties of bacterial haemoglobins.

Bacterial Hbs (haemoglobins), like VHb (Vitreoscilla sp. Hb), and flavoHbs (flavohaemoglobins), such as FHP (Ralstonia eutropha flavoHb), have different autoxidation and ligand-binding rates. To determine the influence of each domain of flavoHbs on ligand binding, we have studied the kinetic ligand-binding properties of oxygen, carbon monoxide and nitric oxide to the chimaeric proteins, FHPg (truncated form of FHP comprising the globin domain alone) and VHb-Red (fusion protein between VHb and the C-terminal reductase domain of FHP) and compared them with those of their natural counterparts, FHP and VHb. Moreover, we also analysed polarity and solvent accessibility to the haem pocket of these proteins. The rate constants for the engineered proteins, VHb-Red and FHPg, do not differ significantly from those of their natural counterparts, VHb and FHP respectively. Our results suggest that the globin domain structure controls the reactivity towards oxygen, carbon monoxide and nitric oxide. The presence or absence of a reductase domain does not affect the affinity to these ligands.