Sabre catalysts containing fluorinated carbon chains for delivery of metal-free mri contrast agents

A method of preparing a hyperpolarized substrate, the method comprising:

• (i) providing a perfluorinated SABRE catalyst comprising a d-block element and a perfluorinated ligand, wherein the perfluorinated ligand is of Formula (I):
• [Lm-(NHC)—(Y—Z)q] Formula (I),
• or a salt thereof, and wherein
• each L is independently selected from hydrogen, adamantyl, a substituted or unsubstituted aromatic group, or a substituted or unsubstituted heteroaromatic group,
• NHC is a 4 to 7-membered N-heterocyclic carbenyl group where NHC is bound to the d-block element via a carbene,
• each Y is independently selected from a bond or a spacer group,
• each Z is a perfluorinated tag,
• m is an integer from 1 to 4, and
• q is an integer from 1 to 3;
• (ii) providing a co-ligand to interact with the perfluorinated SABRE catalyst to facilitate formation of an active perfluorinated SABRE catalyst;
• (iii) combining the active perfluorinated SABRE catalyst with parahydrogen and a substrate comprising a ½ spin nucleus or nuclei in a solvent to obtain a first reaction mixture;
• (iv) hyperpolarizing the first reaction mixture obtained in (iii) by exposing the mixture to a magnetic field or by radiofrequency excitation to obtain a hyperpolarized active perfluorinated SABRE catalyst-substrate and/or a hyperpolarized substrate;
• (v) performing an aqueous phase extraction and/or a fluorinated phase extraction to separate the hyperpolarized substrate from the perfluorinated SABRE catalyst;
• (vi) providing additional co-ligand to interact with the perfluorinated SABRE catalyst to reactivate the perfluorinated SABRE catalyst;
• (vii) combining the reactivated perfluorinated SABRE catalyst with additional parahydrogen and additional substrate comprising a ½ spin nucleus or nuclei in the solvent to obtain a second reaction mixture;
• and
• (viii) hyperpolarizing the second reaction mixture obtained in (vii) by exposing the mixture to a magnetic field or by radiofrequency excitation to obtain additional hyperpolarized active perfluorinated SABRE catalyst-substrate and/or additional hyperpolarized substrate.