Synthesis and structural aspects of pyridine- and imidazole-functionalised bispidines

Bispidines (bispidine = 3,7-diazabicyclo[3.3.1]-nonane) show unique complexation properties towards transition metals. The high thermodynamic stability of the complexes of these structurally reinforced ligands with Cu(II) offers the possibility to apply such complexes for diagnostic and therapeutic purposes (^64/67Cu). Furthermore, the bispidine structure opens suitable chemical approaches to introduce bio-molecules onto the skeleton, an important feature in view of the targeting of such complexes.
We want to present the synthesis and the coordinating properties of novel hexadentate bispidine derivatives having pyridine and/or imidazole units as donor groups. Cu(II) complexes of some bispidines have been isolated and the structures were solved by X-ray single crystal diffraction. As shown in the following figure, the copper(II) complex of the hexadentate bis(amine)tetrakis(pyridine) bispidine ligand L is six-coordinate having a distorted octahedral structure. It is evident from this structure that the copper(II) ion is almost completely shielded from the environment resulting in a very high stability against exogenous competing ligands.
Preliminary labelling experiments of bispidine ligands with ^64/67Cu indicate the rapid formation of stable complexes under mild conditions.