A Chemical Strategy for the Relaxivity Enhancement of Gd-III 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 H-1 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(lp)) was observed (from 20.3 to 37.8 mM(-1) s(-1) 86.2% enhancement at 20 MHz and 310 K), mainly clue to a threefold faster water exchange rate after acetylation of the surface -NH3+ ions. This high r(lp) value, coupled with the large molar amount of grafted 2 onto the silica nanoparticles gives rise to a value of relaxivity per particle of 29500 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.