Aminocarboxylate ligands

Aminocarboxylate ligands have been widely investigated for iron chelation, indeed DTPA (Structure 3) is used in patients who develop toxic side-effects 

---

EDTA is one member of a class of aminocarboxylate ligands that form very stable 1 1 complexes with metal ions. The following table shows log Kf values for several ligands with Ca + and Mg +. Which ligand is the best choice for the direct titration of Ca + in the presence of Mg + ... 

The DELFIA assay, the first effective lanthanide-based immunoassay, was developed and commercialized by the early 1980s.108-112 DELFIA (Dissociation Enhanced Lanthanide Fluoro-ImmunoAssay) is a heterogeneous assay which uses a lanthanide complex based on aminocarboxylate ligands such as EDTA, EGTA, or DTPA, linked to the antibody by reaction of appended isothiocyanate groups (e.g., complex (45)) with nucleophilic residues, particularly amines, on the protein surface (Figure 11). 

Fig. 1. Approximate pH values and ranges for a selection of biochemical and geochemical environments, with their relation to successive pK values for the aminocarboxylate ligand ethylene glycol bis-(2-aminoethyl ether)-tetraacetate, egta.

The strong chelating ability of (multi)amino(multi)carboxylate ligands renders complexes of bismuth substantially more hydrolytically stable than those of bifunctional aminocarboxylate ligands (e.g., glycine). Several compounds have been successfully examined as ligands for bismuth, in that complexes are readily isolable as molecular systems with weak intermolecular interactions. The extent and diversity of these complexes is enhanced by substituent derivatization with, for example, cyclohexyl (e.g., cydtpa) and alkoxyethyl (e.g., oedta) groups. 

The kinetic and activation parameters have been determined for water exchange on several poly(aminocarboxylate) ligands coordinated to Gd together with either one or two coordinated water molecules. In these systems the metal ion is nine-coordinate and the exchange rate constant is reduced by two or three orders of magnitude. [88] Distinctly positive AV values were obtained (D-activation) these could be explained by the steric crowding of the metal ion and the complex ion rigidity relative to the fully aquated ion. 

The labilities of metal-oxygen bonds to hydration waters are similarly enhanced when aminocarboxylate ligands are configured to the metal in a chelate complex (e.g., 18). The effect is progressive rates increase dramatically with the number of amino- or carboxylate- atoms coordinated to the metal (see 15) so that rates of exchange of waters between the inner-coordination sphere of Ni(II) and bulk solution increase by factors of 100-200 for each ammonia or amine substitution in the inner-coordination sphere. In Figure 4, data are presented for Ni(NH ) ( 2 )5-. complexes. 

A new type of aminocarboxylate ligands is the polyazapolycarboxylic acids. These cyclic ligands form a cavity via a ring of ethylene-spaced nitrogen donors with carboxylate "arms which chelate to the metd above and below the plane of the cavity (Figure 7). Complex stabilities of these polyazapolycarboxylates relative to EDTA foUow the sequence ... 

Fig. 4. Correlation of ogjS L w llt logl NdL acetate and a series of aminocarboxylate ligands.

References to kinetic studies of the displacement of a metal cation from its complexes with multidentate aminocarboxylate ligands are listed in Table 37. For the... 

Table 37 Kinetic studies of the displacement of metal ions from aminocarboxylate ligands by other metal ions...

Rate laws for the exchange of Y + with yttrium(m) complexes of the aminocarboxylate ligands edta, cydta, and dtpa have terms in hydrogen ion concentration and in yttrium(in) concentration. The terms in which hydrogen ion concentration, or its square, appears relate to dissociation of mono- and di-protonated forms of the complex. Terms in yttrium(ra) concentration relate to bimolecular attack by the incoming Y +. Yttrium(m) exchange with its hedta complex has a rate law in which the yttrium(m) ion concentration does not appear, so the mechanism here must be purely dissociative. ... 

---