Exploring the Role of the Coordinated 2-Hydroxypropyl Arm in [Ln(HP-DO3A)]: Determining Equilibrium Properties, Prototropic Exchange, Solid-State and Solution Structures

Abstract [Gd(HP-DO3A)] represents the neutral macrocyclic analogue of the negatively charged [Gd(DOTA)]−. Its structure is analogously based on SAP and TSAP geometries. Solid-state X-ray structures of [Ln(HP-DO3A)] (Ln= La(III) and Lu(III)) were acquired. [La(HP-DO3A)] crystals displayed a single molecule in the asymmetric unit endowed with a TSAP structure without coordinated water. Conversely, [Lu(HP-DO3A)] showed two molecules, both with a coordinated water molecule and SAP geometry. New results on the [Eu(HP-DO3A)] solution structure and prototropic exchange were gained by acquiring the 1H NMR spectra in water and in the presence of different buffers at variable temperatures and pH. The difference in the prototropic exchange at the −OH function of the two isomers was assessed. The lower log KEuLH-1 for the −OH function of the SAP diastereomer appears to be the determinant for speciation at basic pH as well as for faster prototropic exchange. Moreover, it was shown that the buffer components affect proton exchange as they can compete with OH– from water dissociation as proton-acceptor partners in base catalysis. This finding was well evident in the CEST response of [Eu(HP-DO3A)] in the presence of bicarbonate/carbonate anions. Furthermore, a new saturation transfer signal at about 2.7 ppm was detected that has been ascribed to a weakening or partial displacement of the OH-bearing arm from the coordination sphere of the Eu(III) ion upon formation of a ternary complex with the carbonate anion in the presence of a large molar excess of the buffer.