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 <i>fac</i>-[M­(CO)₃L¹L²] complexes (M = Re, ^99mTc) containing the (2-hydroxyphenyl)­diphenylphosphine (POH) bidentate ligand (L¹H) and a series of monodentate ligands (L²). First, <i>fac</i>-[Re­(CO)₃(PO)­(H₂O)], <b>1</b>, 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 <i>fac</i>-[Re­(CO)₃(PO)­(POH)], <b>2</b>, 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, <b>1</b> was further used as a precursor to generate a small library of the desired <i>fac</i>-[M­(CO)₃L¹L²] complexes. Specifically, by reaction of triphenylphosphine (PPh₃), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and <i>tert</i>-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%–95%): <i>fac</i>-[Re­(CO)₃(PO)­(PPh₃)], <b>3</b>, <i>fac</i>-[Re­(CO)₃(PO)­(im)], <b>4</b>, <i>fac</i>-[Re­(CO)₃(PO)­(py)], <b>5</b>, <i>fac</i>-[Re­(CO)₃(PO)­(cisc)], <b>6</b>, and <i>fac</i>-[Re­(CO)₃(PO)­(tbi)], <b>7</b>. 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 <b>2′</b>–<b>7′</b> were easily accessible at the ^99mTc-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L² with <i>fac</i>-[^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 <i>fac</i>-[M­(CO)₃(PO)­L²] system for radiopharmaceutical development purposes