A bidentate terephthalamide ligand TAMmeg as an entry into terephthalamide-containing therapeutic iron chelating agents

摘要

A new bidentate 2,3-dihydroxyterephthalamide ligand, 2,3-dihydroxy-N,N′-bis(2-methoxyethyl)terephthalamide (TAMmeg), has been prepared. The ligand, its synthetic precursor 2,3-bis(benzyloxy)-N, N′-bis(2-methoxy-ethyl)-terephthalamide (BnTAMmeg), and its iron complex have been structurally characterized by X-ray diffraction. BnTAMmeg crystallizes in the monoclinic space group P21 with cell parameters a = 14.4976(14) Å, b = 11.5569(11) Å, c = 16.3905(16) Å, β = 113.621(1)°, Z = 4. TAMmeg crystallizes in the monoclinic space group P21/c with cell parameters a = 13.8060(36) Å, b = 8.0049(21) Å, c = 19.4346(50) Å, β = 106.855(4)°, Z = 4. Fe[TAMmeg] crystallizes in the triclinic space group P$\bar{1}$ with cell parameters a = 12.9565(14) Å, b = 13.4514(14) Å, c = 20.2092(21) Å, α = 102.093(2)°, β = 95.433(2)°, γ = 101.532(2)°, Z = 2. The aqueous protonation and ferric ion coordination chemistry of TAMmeg was examined using potentiometric and spectrophotometric methods. Proton association constants and iron complex formation constants for the ligand are as follows: logβ011 = 10.32, logβ012 = 16.49, logβ110 = 17.9, logβ120 = 32.1, logβ130 = 43.0. The ferric complex of TAMmeg is surprisingly stable for a bidentate terephthalamide iron complex. The only more stable bidentate terephthalamide iron complex that has been reported contains a ligand with positively charged pendant arms.