SYNTHESIS, SEPARATION, AND EQUILIBRIUM CHARACTERIZATION OF RACEMIC AND MESO FORMS OF A NEW MULTIDENTATE LIGAND - N,N'-TRIMETHYLENEBIS[2-(2-HYDROXY-3,5-DIMETHYLPHENYL)GLYCINE], TMPHPG

The racemic and meso forms of the EHPG analogue N,N'-trimethylenebis[2-(2-hydroxy-3,5-dimethylphenyl)glycine], TMPHPG, have been separated by exploiting a stability difference in their iron(III) complexes. Assignment of the two diastereomers has been made on the basis of the H-1 NMR spectra of their respective gallium(III) complexes. Ligand protonation and metal ion equilibria with iron(III), gallium(III), and indium(III) have been measured. The increased separation of the two chiral centers relative to that in EHPG (N,N'-ethylenebis[2-(2-hydroxy-3,5-dimethylphenyl)glycine] was found to reduce the stability differences between the diastereomeric complexes. The increased phenol basicity, in combination with the longer diamine bridge length, significantly reduced the effectiveness of these ligands in the binding of indium(III). Calculated pM values indicate that while in vivo exchange of iron(III) and gallium(III) from the complexes to transferrin would be unlikely, indium(III) exchange would be expected.