SYNTHESIS AND CHARACTERIZATION OF MACROBICYCLIC IRON(III) SEQUESTERING AGENTS

This paper reports the template and high-dilution synthesis of a series of macrobicyclic iron(III) sequestering agents based on catechol as the ligating group. An X-ray structure of the salt denoted as Na3[Fe(bicappedTRENCAM)].17.5H2O is the first for any ferric tricatechoyl amide and displays an unprecedented trigonal prismatic coordination (C3h symmetry) for the ferric ion. The compound crystallizes in space group P6(3)/m with a = 13.785 (3) angstrom, c = 16.244 (5) angstrom, d(obs) = 1.45, d(calc) = 1.51 g cm-3. The structure was refined to an R factor of 4.38, R(w) = 5.16. The O-O atoms of the trigonal face are separated by 2.713 (3) angstrom, those related by the mirror plane by 2.526 (4) angstrom. The Fe-O distances are 2.012 (2) angstrom, and the bite angle is 77.75 (11)-degrees. Solution thermodynamic studies on one of the ligands, bicappedTRENCAM, determine surprisingly low protonation constants (log K1K2 = 27.2 (1), log K3 = 8.3 (1), log K4K5 = 8.73 (1), log K6K7K8 = 9.75 (1)) containing a number of polyprotic steps. Aqueous electrochemical studies performed on the ferric complexes of these ligands show reversible reduction potentials of -0.89 to -0.97 V (vs NHE). While still highly selective for the ferric ion (ratios of the formation constants of ferric to ferrous complexes range from 28.1 to 29.5), these ligands have a slight stabilization of the ferrous complex relative to related tripodal compounds, one of which is the siderophore enterobactin. A slow protonation reaction is seen upon reduction of the ferric complexes. The protonation constant of the Fe(bicappedTRENCAM) complex proceeds in an unusual two-proton step with an equilibrium constant of (log K1K2) 10.65 (1). The complex formation constant (log K) is 43.1 (4), which shows no increase due to the macrobicyclic structure of the ligand relative to related hexadentate catechol ligands. The pM value is 30.7, where pM = -log [Fe] at pH 7.4 and [Fe]T = 10(-6) M, [L]T = 10(-5) M.