TECHNETIUM(V) AND RHENIUM(V) COMPLEXES OF 2,3-BIS(MERCAPTOACETAMIDO)PROPANOATE - CHELATE RING STEREOCHEMISTRY AND INFLUENCE ON CHEMICAL AND BIOLOGICAL PROPERTIES

Monoxo complexes of technetium(V) and rhenium(V) with 2,3-bis(mercaptoacetamido)propanoate (map) have been synthesized. The complexes with general formula [Ph4X][MO(map)] (where X = As, P; M = Tc, Re) were characterized by IR, visible-UV spectra, and negative ion fast atom bombardment spectroscopy. The chelate ring epimers were separated by HPLC (semipreparative reverse-phase C18) isolated and crystallized as salts of [Ph4X][MO(map)]. The structures of the two epimers (syn and anti) of technetium and one of the epimers (syn) of the rhenium complexes were determined by single-crystal X-ray analyses. All three complexes crystallize in the space group P21/c and have four formula units in the unit cell. The crystal data for [Ph4As][syn-TcO(map)] are as follows: a = 12.729 (1) Å, b = 13.225 (2) Å, c = 18.318 (2) Å, β = 91.67 (1) °, v = 3082.4 (6) Å3, and R = 0.059. For the complex, [Ph4P][anti-TcO(map)], the crystal data are as follows: a = 11.260 (2) Å, b = 23.622 (3) Å, c = 11.834 (3) Å, β = 94.52 (2)°, v = 3138 (1) Å3, and R = 0.057. The corresponding parameters for [Ph4As][syn-ReO(map)] are 12.749 (4) Å, 13.189 (2) Å, 18.311 (6) Å, 91.63 (3)°, 3078 (2) Å3, and 0.049. In all of the three complexes, the metal (Tc, Re) is coordinated to one oxygen (yl) atom, two sulfur (thiolate) atoms, and two nitrogen atoms (amide) in a distorted square-pyramidal geometry. The position trans to the oxygen (yl) atom is vacant. The metal atom is 0.747 ± 0.005 Å above the basal plane (N2S2). The mean M-O, M-N, and M-S bond lengths are 1.654, 1.979, and 2.283 Å, respectively, and are in good agreement with the bond lengths in similar complexes. There is no bonding between the carboxylic acid group of the ligand and the metal or yl oxygen atom. The tetrafluorophenyl ester derivatives of the complexes were prepared by the carbodiimide coupling method. The HPLC profile of the complexes and their ester derivatives are consistent with the polarity of the complexes and the nature of column material. Even though the structures of syn epimers of Tc and Re complexes are similar, contrary to expectations, the order of elution of the Tc and Re epimers is reversed on the C18 reverse-phase column with the anti Tc complex epimer significantly retarded. The influence of the chelate ring stereochemistry on the rates of renal excretion and the applications of the chelates for the radiolabeling of monoclonal antibodies are discussed. © 1990, American Chemical Society. All rights reserved.