RHENIUM(VI) OXO COMPLEXES RELEVANT TO TECHNETIUM RENAL IMAGING AGENTS DERIVED FROM MERCAPTOACETYLGLYCYLGLYCYLAMINOBENZOIC ACID ISOMERS - STRUCTURAL AND MOLECULAR MECHANICS STUDIES

The synthesis and characterization of three rhenium(V) oxo complexes derived from isomers of mercaptoacetylglycylglycylaminobenzoic aminobenzoic acid (MAG2-ABAH5) are reported. The isomers were synthesized from o-, m- and p-aminobenzoic acid and differed in the position of the terminal carboxyl group. The anions of 8-10, [ReO(MAG2-*ABAH)]- (* = para (8), meta (9), ortho (10)), contained the tetraanionic form of the ligands with the carboxyl group protonated. 8, 9, and 10 were synthesized by exchange reactions of ReOCl3(Me2SO)(Ph3P) under moderate conditions and were isolated as [Ph4P]+, [Bu4N]+, and [Ph4P]+ salts, respectively. The structures of 8 and 10 were determined by X-ray diffraction methods; except for the location of the carboxyl group, the structures are similar. The coordination geometry is pseudo square pyramidal, with nitrogen and sulfur donor atoms forming a square base and the oxo ligand at the apex. The orientation of the carboxyl group in 10 is anti to the Re=O group. Crystal data for 8: chemical formula C37H33N3O7PReS, a = 10.985 (5) angstrom, b = 12.320 (5) angstrom, c = 14.417 (8) angstrom, alpha = 93.67 (4)-degrees, beta = 106.63 (4)-degrees, gamma = 104.78 (3)-degrees, V = 1787.9 (14) angstrom3, triclinic, space group P1BAR, Z = 2. Crystal data for 10: chemical formula C37H31N3O6PReS, a = 11.066 (4) angstrom, b = 19.436 (7) angstrom, c = 16.495 (6) angstrom, beta = 107.73 (3)degrees, V = 3379.4 (11) angstrom3, monoclinic, space group P2(1)/c, Z = 4. Since the carboxyl groups are protonated in 8 and 10 and in other relevant structures from this class of radiopharmaceuticals including [Ph4As][TcO(MAG3H)] (MAG3H = tetraanionic form of mercaptoacetyltriglycine), we developed molecular mechanics parameters that allowed us to calculate the structures of 8, 10, and [TcO(MAG3H)]-. We then extended the calculations to all three isomeric complexes in their deprotonated forms and to [TcO(MAG3)]2- in order to approximate their solution phase structures. We conclude that the [TcO(MAG3)]2- species is conformationally flexible, and we have made an initial assessment of structures vs renal clearance.