2 + 1 Tricarbonyl Complexes of Technetium(I) with a Combination of N,N-Bidentate Ligands and Ethyl Isocyanoacetate: How Strong Is the Interfering Effect of Chloride Ions on Their Formation?

Technetium(I) 2 + 1 tricarbonyl complexes with a combination of N,N-bidentate ligands (2,2'-bipyridine, bipy; 1,10-phenanthroline, phen) and ethyl isocyanoacetate were prepared and characterized by NMR, IR, UV/visible, and luminescence spectroscopies and by high-performance liquid chromatography (HPLC). The crystal structures of [99Tc(CO)3(bipy)(CNCH2COOEt)](ClO4) (in the form of a solvate with 0.5CH2Cl2) and [99Tc(CO)3(phen)(CNCH2COOEt)](ClO4) (in the form of an adduct with an outer-sphere phen molecule) were determined by single-crystal X-ray diffraction. To evaluate the interfering effect of chloride ions on the formation of the 2 + 1 complexes, the kinetics of the replacement of labile monodentate ligand X in the complexes [MX(CO)3(N∧N)] (M = Re, 99Tc; N∧N = bipy, phen; X = Cl-, ClO4-) by CNCH2COOEt in ethanol were compared. The 99Tc bipy complexes with X = ClO4- (according to the IR data, perchlorate anion in ethanol is displaced from the coordination sphere by the solvent molecule) and X = Cl- are characterized by close ligand replacement rates. In the case of the 99Tc complexes with phen and Re complexes with both phen and bipy, the chloride complexes are appreciably less reactive than the chloride-free complexes. The technetium complexes are considerably more reactive in ligand replacement than their rhenium analogues. In the chloride-containing medium (saline), the complex [99mTc(CO)3(bipy)(CNCH2COOEt)]+ can be prepared under the conditions acceptable for nuclear medical applications, although higher isonitrile concentrations are required as compared to the chloride-free system.

Technetium and rhenium pentacarbonyl complexes with C2 and C11 ω-isocyanocarboxylic acid esters.

Technetium(I) and rhenium(I) pentacarbonyl complexes with ethyl 2-isocyanoacetate and methyl 11-isocyanoundecanoate, [M(CO)5(CNCH2COOEt)]ClO4 (M = Tc (1) and Re (2)) and [M(CO)5(CN(CH2)10COOMe)]ClO4 (M = Tc (3) and Re (4)), were prepared and characterized by IR, (1)H NMR, and (13)C{(1)H} NMR spectroscopy. The crystal structures of 1 and 2 were determined using single-crystal X-ray diffraction. The kinetics of thermal decarbonylation of technetium complexes 1 and 3 in ethylene glycol was studied by IR spectroscopy. The rate constants and activation parameters of this reaction were determined and compared with those for [Tc(CO)6](+). It was found that rhenium complexes 2 and 4 were stable with respect to thermal decarbonylation. Histidine challenge reaction of complexes 1 and 2 in phosphate buffer was examined by IR spectroscopy. In the presence of histidine, the rhenium pentacarbonyl isocyanide complex partially decomposes to form an unidentified yellow precipitate. Technetium analogue 1 is more stable under these conditions.

Synthesis, characterization and pre-clinical evaluation of (99m) Tc-tricarbonyl complexes as potential myocardial perfusion imaging agents.

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. (99m) Tc(CO)3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.