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

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journal contribution
posted on 04.09.2020, 22:03 by Shaunna M. McLeod, Lee Robison, Giacomo Parigi, Alyssa Olszewski, Riki J. Drout, Xinyi Gong, Timur Islamoglu, Claudio Luchinat, Omar K. Farha, Thomas J. Meade
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.