Isomeric DTPA-amide macrocycles of p-xylenediamine and their complexation with Gd3+

Three DTPA-amide cyclophanes – including conformational isomers – have been isolated by optimizing the conditions of a reaction between diethylenetriaminepentaacetic (DTPA) dianhydride and p-xylenediamine: a 2 + 2-cyclization product, abbreviated as (cy2)H6, that integrates two phenylene groups in the macrocyclic frame and bears six pendant –CH2CO2H arms, and two isomeric 1 + 1-macrocyles, (cy1)H3, carrying three arms. A crucial factor for controlling the ring size is the concentration in the reaction. For (cy2)H6, whose binuclear Gd3+ complex is a potential paramagnetic protein sensor, the synthetic method has been established in 70% yield. The isomerism of (cy1)H3 is due to the conformation of the rigid macrocyclic frame; the 1H NMR and geometry optimization show that the conformation is of quasi-C2 symmetry in one (cy1)H3 isomer, and of quasi-mirror symmetry in the other. Their distinct conformations define the chemical properties and coordination capability toward Gd3+: in the C2-symmetric isomer, the amino nitrogen is less basic and the N–H bond is more covalent than in the mirror-symmetric isomer; the former forms a mononuclear Gd3+ complex whereas the latter does not show sign of complexation with Gd3+.

Three macrocycles have been isolated from reactions between DTPA dianhydride and p-xylenediamine: a 2 + 2-cyclization macrocycle in a high yield, and two 1 + 1-macrocyclic isomers which differ in coordination capability toward Gd3+.Figure optionsDownload as PowerPoint slide