Fluorescent aza-cyclophanes derived from diethylenetriaminepentaacetic acid (DTPA), and their complexation with Gd(III)

Chelating aza-cyclophanes were synthesized by reactions of diethylenetriaminepentaacetic acid (or DTPA) dianhydride with aromatic diamines, 4,4′-diaminobibenzyl (DAB) and 4,4′-bis(1,1′-biphenyl-4,4′-diyldioxy)dianiline (BPA). The former amine gave a 2:2-cyclization product bearing six –CH2CO2H arms, 2,12,29,39-tetraoxo-4,7,10,31,34,37-hexakis(carboxymethylene)-1,4,7,10,13,28,31,34,37,40-decaaza-[13.2.13.2]ethylenparacyclophane, abbreviated as cy(bisdtpadab)H6, whereas BPA yielded a 1:1-cyclization product carrying three –CH2CO2H arms, 2,12-dioxo-4,7,10-trakis(carboxymethylene)-1,4,7,10,13-pentaaza-20,33-dioxa[13.0.1]paracyclophane, abbreviated as cy(dtpabpa)H3. Their protonation and complexation with Gd(III) were studied by fluorescence spectra, 1H NMR and potentiometry. The macrocyclic framework of cy(dtpabpa)H3 has a high rigidity; as a consequence, this ligand is incapable of forming a complex with Gd(III). In contrast, cy(bisdtpadab)H6, which is moderately rigid, forms a binuclear Gd(III) complex, as confirmed by a sensitive quenching of the fluorescence upon complexation. On the basis of the pH dependence of the fluorescence spectra, the logarithmic overall formation constants were determined as log βM2L = 28.3, log βM2LH = 31.9, log βM2LH−1 = 21.0, logβM2LH−2 = 9.8. For the chelating cyclophanes, the rigidity is one of major controlling factors for the stability of their complexes. The sharp change in the fluorescence intensity upon complexation with Gd3+ ion suggests that the chelating cyclophane works potentially as fluorescent probes toward specific metal ions.

Reactions between DTPA dianhydride and selected aromatic diamines yield 1:1- and 2:2-cyclization products with amide linkages, depending on relative chain lengths of the reactants; fluorescence spectra indicate that the 1:1-macrocycle I does not react with Gd(III) ion for steric reason but the 2:2-macrocycle forms a stable binuclear Gd(III) complex II.Figure optionsDownload as PowerPoint slide