Maximizing Magnetic Resonance Contrast in Gd(III) Nanoconjugates: Investigation of Proton Relaxation in Zirconium Metal–Organic Frameworks

Gadolinium­(III) nanoconjugate contrast agents (CAs) provide significant advantages over small-molecule complexes for magnetic resonance imaging (MRI), namely increased Gd­(III) payload and enhanced proton relaxation efficiency (relaxivity, r₁). Previous research has demonstrated that both the structure and surface chemistry of the nanomaterial substantially influence contrast. We hypothesized that inserting Gd­(III) complexes in the pores of a metal–organic framework (MOF) might offer a unique strategy to further explore the parameters of nanomaterial structure and composition, which influence relaxivity. Herein, we postsynthetically incorporate Gd­(III) complexes into Zr-MOFs using solvent-assisted ligand incorporation (SALI). Through the study of Zr-based MOFs, NU-1000 (nano and micronsize particles) and NU-901, we investigated the impact of particle size and pore shape on proton relaxivity. The SALI-functionalized Gd nano NU-1000 hybrid material displayed the highest loading of the Gd­(III) complex (1.9 ± 0.1 complexes per node) and exhibited the most enhanced proton relaxivity (r₁ of 26 ± 1 mM^–1 s^–1 at 1.4 T). Based on nuclear magnetic relaxation dispersion (NMRD) analysis, we can attribute the performance of Gd nano NU-1000 to the nanoscale size of the MOF particles and larger pore size that allows for rapid water exchange. We have demonstrated that SALI is a promising method for incorporating Gd­(III) complexes into MOF materials and identified crucial design parameters for the preparation of next generation Gd­(III)-functionalized MOF MRI contrast agents.