Abstract
The lead(II) coordination properties of the tetrapodal ligand DOTAM [1,4,7,10‐tetrakis(carbamoylmethyl)‐1,4,7,10‐tetraaza‐cyclododecane] have been investigated both in the solid state and in solution in order to ascertain the stereoactivity of the lone pair and to rationalize the structural effects of a cyclen‐based scaffold on the metal uptake kinetics. The crystal structure of the free base shows that the pendant acetamide groups are not equivalent: two are folded over the macrocycle and maintained by an intramolecular hydrogen bond involving an amide hydrogen atom and a neighboring tertiary amine of the cyclen ring, while the other two are extended and point away from the macrocyclic cavity. The spontaneous reaction between Pb^2+^ and DOTAM, even under mild acidic conditions, leads to a mononuclear complex. The crystal structure of Pb(DOTAM)~2~**·**3.5H~2~O reveals that the eight‐coordinate metal cation is trapped inside the core of the ligand, interacting with the four cyclen nitrogen and the four amide oxygen atoms. The helical layout of the folded arms leaves no significant gap in the coordination sphere of Pb^2+^, thus leading to a holodirected structure that is characteristic of a stereochemically inactive 6s^2^ electronic lone pair. While the coordination scheme is maintained in solution, variable temperature NMR studies enabled characterization of the dynamics related to the inversion of configuration of the amide substituents. Finally, the lead(II)‐binding mechanism in aqueous solution has been investigated over a wide p[H] range (1–7) by means of classical and stopped‐flow spectrophotometry. The complexation reaction proceeds in a single rate‐limiting step according to an Eigen–Winkler mechanism. (© WILEY‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)