Supramolecular Adducts of Negatively Charged Lanthanide(III) DOTP Chelates and Cyclodextrins Functionalized with Ammonium Groups: Mass Spectrometry and Nuclear Magnetic Resonance Studies

Abstract

The interaction of the negatively charged Ln3+ chelate Ln–DOTP with β‐ and γ‐cyclodextrins bearing ammonium groups at the upper rim (CD+s) was investigated using mass spectrometry and NMR spectroscopic techniques. Mass spectroscopy shows the presence of 1:1 adducts of Ln–DOTP and both β‐ or γ‐CD+. The peak intensities increased upon increasing the pH of the samples from 7 to 9.0, suggesting an increase in the strength of the interaction. Lanthanide induced 1H NMR chemical shifts and relaxation ratesmeasured in aqueous solutions confirmed the presence of these adducts. The strength of the interactions appeared to be dependent on the pH, reflecting the strong electrostatic interactions between the oppositely charged host CD+ and guest Ln–DOTP chelate. Evaluation of the lanthanide induced relaxation rates showed that the Ln–DOTP does not enter the cavity of the CDs, but remains above it with a distance of 10–11 Å between the Ln3+ ion and the centre of the CD. Molecular modelling indicated that hydrogen bonds between the functionalized groups participating in the interaction sites contribute to the adduct stabilization. The apparent binding constants at pH 7 and 9 were obtained by using relaxometric measurements at 9 MHz. Fitting the NMRD profiles showed an increase in the number of second‐sphere water molecules surrounding the phosphonate pendant arms of the Ln–DOTP chelate upon its interaction with the CDs. A brief description of the PARACEST properties of the supramolecular systems formed by Tm–DOTP and the positively charged CDs is presented. Both CDs display a shift of the saturation transfer peaks of the ammonium functions by the Tm complex, with an accentuated effect observed for the γ‐CD derivative.

Crosslinked shells for nano-assembled capsules: a new encapsulation method for smaller Gd3+-loaded capsules with exceedingly high relaxivities

“…22-25 GdDOTP 5- is capable of a very large number of “second-sphere” interactions, 12, 26 which leads to a high second sphere contribution to relaxivity that may be enhanced by causing the chelate to tumble more slowly. 27, 28 These second-sphere interactions are responsible for anchoring the chelate within the capsule interior. Presumably these interactions hold the chelate quite rigidly in 3-dimensions which will tend to couple the molecular motion of GdDOTP 5- to that of the nano-capsule more effectively.…”

Lanthanopolyoxometalate‐Silica Core/Shell Nanoparticles as Potential MRI Contrast Agents

“…However, the observed relaxivities are too high to be explained solely by the OS contribution, which is expected to be small due to the large value of a resulting from the bulky POM ligands coordinating the Gd 3+ ion. They can be explained by a large contribution from a 2 nd ‐sphere relaxation mechanism [56,57] comprising the dipolar interaction of Gd 3+ with a considerable number ( q ’) of water molecules being held for times longer than the translational correlation time (τ d ), in the second coordination shell of Gd 3+ at a distance r ’ by hydrogen bonding interactions with the nearby W−O negatively charged oxygen atoms, but that are not directly bound to Gd 3+ (Figure 1A). This reasoning is supported by the presence of a large number of water molecules of crystallization involved in an extensive hydrogen bonded network with the [W 5 O 18 ] 6− anions and the counterions in the crystal structure of the LaPOM [50] .…”

Nuclear spin relaxation in liquids and gases

“…Pereira et al 211 studied adducts of negatively charged lanthanide chelates with cyclodextrins, functionalized with ammonium groups. In the case of Gd(III) complexes, the authors measured PRE for aqueous protons by the field cycling technique.…”