Polyaminopolycarboxylic acid chelating

The general interests in chelation of metals have continued to lead to new forms of polyaminopolycarboxylic acids. Examination of the acid dissociation constant of ethyl-ene-bis-N,N -(2,6-dicarboxy)piperidine (9) showed that they were nearly identical with those of EDTA. However, the formation constants for metal chelates of (9) are lower by 0.5 to 3.7 log 3 units. 

Interest in the coupling of polyaminopolycarboxylic acids to macromolecules for use in nuclear medicine resulted in the synthesis of l-(p-aminophenyl)-ethylenediaminetet-raacetic acid (10, n = 0, R=NH2, pAPhEDTA). Since its first synthesis there have been improvements in its synthesis105 as well as the synthesis of related chelating agents (10, n = 2)106, (ll)107 and (12)108. In a search for a lipophilic chelator which could be incorporated into the lipid phase of liposomes, Bard et al.109 synthesized 3-cholesteryl 6-[N -iminobis(ethylenenitrilo)-tetraacetic acidjhexylether (13). 

As fatty acids are taken up into the myocardium, Karesh et al.134) incorporated similar structures into polyaminopolycarboxylic acids, radiolabelled them with "mTc and 57Co and examined them for myocardial imaging. These chelators, which possessed chelating moieties similar to DTPA, had a low uptake into the heart (<0.94%) but showed an uptake into the liver of 16%. 

In 1945 Schwarzenbach published the first of a series of fundamental studies of polyaminopolycarboxylic acids as analytical chelating reagents. Of these, ethylene-diaminetetraacetic acid, usually abbreviated EDTA, has become one of the most important of all the reagents used in titrimetry. Another important contribution made by Schwarzenbach and his coworkers was the development of indicators that respond to changes in metal ion activity. 

Table 7.2 Some of the more common polyaminopolycarboxylic acids used in chelation therapy. The active form is the negatively charged anion, but the agent is administered in the acid or salt form having protons and sodium, zinc, etc. cations added to neutralize the anion...

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