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 pK a values. The use of these complexes as catalysts in the transfer of polarisation from para-hydrogen to pyridazine and phthalazine via signal amplification by reversible exchange (SABRE) is explored. The possible future use of drugs which contain pyridazine and phthalazine motifs as in vivo or clinical magnetic resonance imaging probes is demonstrated; a range of NMR and phantom-based MRI measurements are reported.