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.