Iron chelating groups binding

A more complex set of 1,3,5-benzenetricarboxamids, composed of mono- di- and tritopic iron chelating groups, prepared by Tsubouchi and coworkers", showed that tripodal hydroxamates 47 and 48 were able to form tripodal interstrand complexes with one and two iron(III) ions. The tritopic hydroxamate 49 formed preferably ferrioxamine-like intrastrand structures, where each arm binds an iron(III) ion independently. No microbial activity was reported for 47-49. 

Iron chelators can also be used to selectively bind iron in areas where oxidative stress is observed, thereby preventing the iron from taking part in Fenton reactions without interfering with normal iron homeostasis. Charkoudian et al. have developed boronic acid and boronic ester masked prochelators, which do not bind metals unless exposed to hydrogen peroxide (237,238). The binding of these chelators to iron(III) prevents redox cycling. Similar studies of these systems have been performed by a separate group (239,240). 

Another example related to therapeutics involves hydroxamic acids, which have been widely used as a key functional group of potential therapeutics targeting at zinc-bound matrix metalloproteinases involved in cancers [7]. But the hydroxamic acids are also iron chelators [8], and since iron is the most abundant transition metal ion present in the human body, studies are being conducted in order to find new stable conformers and tautomers of hydroxamic acids that would preferentially bind to zinc. 

In positions so that six stable bonds can be formed to chelate Iron. Such a molecule Is desferrioxamlne or Desferal three hydroxamlc acids are separated by several carbons to provide adequate spacing for the Iron binding groups along with several additional oxygens and nitrogens to make the molecule more water soluble. This Iron chelator Is effective In man. 

The second group of compounds, which are the catechols, are represented by enterobactln, which has three catechol groups (and, therefore, six bonds) (Figure 6). This Iron chelator, which will be discussed In detail by both Dr. Nellands and Dr. Raymond and appears to have the highest Iron binding constant yet measured, Is Isolated from E. coll and Is composed of three Identical subunits of 2,3-dlhydroxybenzolc acid attached to a serine. If the serine Is removed, the simple molecule, 2,3-dlhydroxybenzolc acid. Is obtained. The Rockefeller group have shown that 2,3-dlhydroxybenzolc acid Is a moderately effective oral Iron chelator (10). 

In the presence of compounds with a higher (in comparison with Fe ions) affinity for NO or NO (e.g., heme groups or thiols), the latter bind to NO or NO" released from DNIC as a result of which the chemical equilibriiun is shifted to the right and gradual decomposition of DNIC occurs. Similar events take place during irreversible decomposition of DNIC induced by, for example, iron chelators able to interact directly with DNIC or oxidants causing selective oxidation of iron in DNIC. 

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