Intermolecular interactions of highly stable paramagnetic lanthanide(III) chelates as studied by nuclear magnetic resonance spectroscopy

The paramagnetic C-13 NMR relaxation rate enhancements and the H-1 induced chemical shifts of a series of organic molecules, caused by various paramagnetic metal complexes and a nitroxide radical (TEMPOL), were measured in aqueous solution. These NMR perturbations were used to study and model the mechanisms of their non-covalent intel actions. The paramagnetic metal complexes showed a varying degree of binding specificity, in contrast to the non-specific interactions of the nitroxide radical. Weak and basically non-specific binding was observed for the neutral DTPA-bis(amide) complexes, possibly due to hydrophobic interactions, whereas the single negatively charged DOTA and DOTP-MB complexes showed weak specific interactions with ammonium functions. The strongest and most specific interactions occurred between the negatively charged Ln(DOTP) chelates and the protonated linear and macrocyclic amines. In the case of Ln(DOTP)-ADA, the H-1 induced shifts and C-13 spin-lattice relaxation rates were fitted to the theoretical equations, yielding a geometry for the adduct where the ammonium group interacts with the Ln-unbound negatively charged oxygen(s) of one phosphonate group. Two Ln( DOTP) molecules appear to be able to sandwich the diprotonated tetraazamacrocyclic amine CY. In the polyhydroxyammonium compound MEG, the strong electrostatic interaction is assisted by hydrogen bonding of hydroxyl groups to the Ln-unbound phosphonate oxygens of DOTP. A comparison of the strong pH dependences found for the paramagnetic NMR effects of the Ln(DOTP) chelates on the H-1 and C-13 nuclei of CY and MEG clearly indicated the dominance of the electrostatic interactions in both cases. Considering the organic molecules used as good models of side-chains of amino-acid residues at the surface of proteins, the observed interactions allow specific probing of protein surfaces using NMR methods.