A Chemical Strategy for the Relaxivity Enhancement of GdIII Chelates Anchored on Mesoporous Silica Nanoparticles

Functionalised MCM‐41 mesoporous silica nanoparticles were used as carriers of Gd^III complexes for the development of nanosized magnetic resonance imaging contrast agents. Three Gd^III complexes based on the 1,4,7,10‐tetraazacyclododecane scaffold (DOTA; monoamide‐, DOTA‐ and DO3A‐like complexes) with distinct structural and magnetic properties were anchored on the silica nanoparticles functionalised with NH₂ groups. The interaction between Gd^III chelates and surface functional groups markedly influenced the relaxometric properties of the hybrid materials, and were deeply modified passing from ionic ? NH₃⁺ to neutral amides. A complete study of the structural, textural and surface properties together with a full ¹H relaxometric characterisation of these hybrid materials before and after surface modification was carried out. Particularly for the anionic complex 2 attached to MCM‐41, an impressive increase in relaxivity (r_1p) was observed (from 20.3 to 37.8 mM ^?1 s^?1, 86.2 % enhancement at 20 MHz and 310 K), mainly due to a threefold faster water exchange rate after acetylation of the surface ? NH₃⁺ ions. This high r_1p value, coupled with the large molar amount of grafted 2 onto the silica nanoparticles gives rise to a value of relaxivity per particle of 29 500 mM ^?1 s^?1, which possibly allows it to be used in molecular imaging procedures. Smaller changes were observed for the hybrid materials based on neutral 1 and 3 complexes. In fact, whereas 1 shows a weak interaction with the surface and acetylation induced only some decrease of the local rotation, complex 3 appears to be involved in a strong interaction with surface silanols. This results in the displacement of a coordinated water molecule and in a decrease of the accessibility of the solvent to the metal centre, which is unaffected by the modification of ammonium ions to neutral amides.