Investigating pyridazine and phthalazine exchange in a series of iridium complexes in order to define their role in the catalytic transfer of magnetisation from para-hydrogen

Abstract

The reaction of [Ir(IMes)(COD)Cl], [IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, COD = 1,5-cyclooctadiene] with pyridazine (pdz) and phthalazine (phth) results in the formation of [Ir(COD)(IMes)(pdz)]Cl and [Ir(COD)(IMes)(phth)]Cl. These two complexes are shown by nuclear magnetic resonance (NMR) studies to undergo a haptotropic shift which interchanges pairs of protons within the bound ligands. When these complexes are exposed to hydrogen, they react to form [Ir(H)₂(COD)(IMes)(pdz)]Cl and [Ir(H)₂(COD)(IMes)(phth)]Cl, respectively, which ultimately convert to [Ir(H)₂(IMes)(pdz)₃]Cl and [Ir(H)₂(IMes)(phth)₃]Cl, as the COD is hydrogenated to form cyclooctane. These two dihydride complexes are shown, by NMR, to undergo both full N-heterocycle dissociation and a haptotropic shift, the rates of which are affected by both steric interactions and free ligand p<i>K</i>_a values. The use of these complexes as catalysts in the transfer of polarisation from <i>para</i>-hydrogen to pyridazine and phthalazine <i>via</i> signal amplification by reversible exchange (SABRE) is explored. The possible future use of drugs which contain pyridazine and phthalazine motifs as <i>in vivo</i> or clinical magnetic resonance imaging probes is demonstrated; a range of NMR and phantom-based MRI measurements are reported.