Exploiting the Fluxionality of Lanthanide Complexes in the Design of Paramagnetic Fluorine Probes

Randall K. Wilharm, Mandapati V. Ramakrishnam Raju, John C. Hoefler, Carlos Platas-Iglesias, Valérie C. Pierre

Research output: Contribution to journalArticlepeer-review

Abstract

Fluorine-19 MRI is increasingly being considered as a tool for biomolecular imaging, but the very poor sensitivity of this technique has limited most applications. Previous studies have long established that increasing the sensitivity of 19F molecular probes requires increasing the number of fluorine nuclei per probe as well as decreasing their longitudinal relaxation time. The latter is easily achieved by positioning the fluorine atoms in close proximity to a paramagnetic metal ion such as a lanthanide(III). Increasing the number of fluorine atoms per molecule, however, is only useful inasmuch as all of the fluorine nuclei are chemically equivalent. Previous attempts to achieve this equivalency have focused on designing highly symmetric and rigid fluorinated macrocyclic ligands. A much simpler approach consists of exploiting highly fluxional lanthanide complexes with open coordination sites that have a high affinity for phosphated and phosphonated species. Computational studies indicate that LnIII-TREN-MAM is highly fluxional, rapidly interconverting between at least six distinct isomers. In neutral water at room temperature, LnIII-TREN-MAM binds two or three equivalents of fluorinated phosphonates. The close proximity of the 19F nuclei to the LnIIIcenter in the ternary complex decreases the relaxation times of the fluorine nuclei up to 40-fold. Advantageously, the fluorophosphonate-bound lanthanide complex is also highly fluxional such that all 19F nuclei are chemically equivalent and display a single 19F signal with a small LIS. Dynamic averaging of fluxional fluorinated supramolecular assemblies thus produces effective 19F MR systems.

Original languageEnglish (US)
Pages (from-to)4130-4142
Number of pages13
JournalInorganic chemistry
Volume61
Issue number9
DOIs
StatePublished - Mar 7 2022

Bibliographical note

Funding Information:
The authors thank the National Institutes of Health for the support provided by R01 DK124333-01A1.

Publisher Copyright:
© 2022 American Chemical Society.

PubMed: MeSH publication types

  • Journal Article

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