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.