Rhenium(I) Tricarbonyl Complexes with (2-Hydroxyphenyl)diphenylphosphine as PO Bidentate Ligand

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)₃L¹L²] complexes (M = Re, ^99mTc) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand (L¹H) and a series of monodentate ligands (L²). First, fac-[Re(CO)₃(PO)(H₂O)], 1, was synthesized by reaction of POH and [Et₄N]₂[Re(CO)₃Br₃] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)₃(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand. Owing to the presence of the labile aqua ligand, which can be readily replaced by various monodentate ligands, 1 was further used as a precursor to generate a small library of the desired fac-[M(CO)₃L¹L²] complexes. Specifically, by reaction of triphenylphosphine (PPh₃), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and tert-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%-95%): fac-[Re(CO)₃(PO)(PPh₃)], 3, fac-[Re(CO)₃(PO)(im)], 4, fac-[Re(CO)₃(PO)(py)], 5, fac-[Re(CO)₃(PO)(cisc)], 6, and fac-[Re(CO)₃(PO)(tbi)], 7. All compounds were fully characterized by elemental analysis, IR and NMR spectroscopies, and electrospray ionization(+) mass spectrometry. Their solid-state structure was elucidated by X-ray crystallography. Of considerable interest is the fact that the corresponding 2'-7' were easily accessible at the ^99mTc-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L² with fac-[^99mTc(CO)₃(H₂O)₃]⁺ in aqueous MeOH, as verified by comparative chromatographic methods adopting dual photo- and radiometric detection modes. The high stability displayed by all ^99mTc complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)₃(PO)L²] system for radiopharmaceutical development purposes.