title: A modular system for the synthesis of multiplexed magnetic resonance probes.
abstract: We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multinuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology and Physiology, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mastarone
authors.forename: Victoria S R
authors.initials: VS
authors.lastname: Harrison
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Eckermann
authors.forename: Giacomo
authors.initials: G
authors.lastname: Parigi
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D057930:Click Chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D005682:Gadolinium / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature
chemical_list: D000480:Alkynes; D001386:Azides; D002614:Chelating Agents; D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium