STRUCTURE AFFINITY RELATIONSHIPS IN THE BINDING OF UNSUBSTITUTED IRON PHENOLATE COMPLEXES TO HUMAN SERUM-ALBUMIN - MOLECULAR-STRUCTURE OF IRON(III) N,N'-BIS(2-HYDROXYBENZYL)ETHYLENEDIAMINE-N,N'-DIACETATE

Structure-affinity relationships in the binding of iron(III) ethylene-N,N′-bis((2-hydroxyphenyl)glycinate) [Fe(EHPG)−] diastereomers and iron(III) N,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetate [Fe(HBED)−] to human serum albumin (HSA) are elucidated with equilibrium dialysis and water proton NMR relaxation studies. Fe(HBED)− and the racemic (RR + SS) isomer of Fe(EHPG)− bind to one apparent site on HSA with association constants on the order of (1.1–1.7) × 103 M−1, whereas the meso (RS) isomer of Fe(EHPG)− binds only weakly. The relative affinities are apparently a function of phenolate ring orientation: the cis-equatorial phenolate coordination exhibited by rac-Fe(EHPG)− and Fe(HBED)− leads to a cylindrical shape that may be more complementary with a cleftlike site on the protein surface than the more distorted meso-Fe(EHPG)− isomer, which has one axial and one equatorial phenolate. The outer-sphere relaxivities of all three complexes increase by factors of 3–4 upon binding to the protein due to the increased rotational correlation time; this enhancement is consistent with the chelates binding on the protein surface. An X-ray structural analysis was performed on K[Fe(HBED)]•CH3OH•CHCl3, which crystallizes in the monoclinic P21/a space group, with a = 12.589 (2) Å, b = 17.414 (2) Å, c = 12.727 (2) Å, β = 102.54°, and Z = 4. © 1990, American Chemical Society. All rights reserved.