Tricarbonylrhenium (I) complexes with neutral bidentate N-methyl-2-pyridinecarboamide as a precursor of therapeutic radiopharmaceuticals

Coordination chemistry of technetium and rhenium attracts considerable interest due to the nuclear medicine applications of their radionuclides. 99mTc (γ-emitter) is the 'working horse' in diagnostic nuclear medicine, used in more than 80 percent of routine studies in this field. The β- -emitting rhenium isotopes, 186Re and 188Re, are used in radioimmuno therapy. The coordination behaviour of tricarbonylmetal(I) with chelating ligands, important for designing new metal-based radiopharmaceuticals, has been intensively studied by numerous authors. Particularly stable bonds have been found between the [M(CO)3]+ core (M Re, Tc) and aromatic nitrogen donor atoms of multidentate ligands. In this paper we report the complex formation (in mg quantities) of the tricarbonylrhenium(I) moiety with N-methyl-2-pyridinecarboamide (1), an analogue of the thio-compound recently studied. Ligand 1 was obtained according to the general procedure described in. The Re(I) precursor (2) was obtained. The investigated complex [ReI(CO)3LCl] (3), where L denotes 1, was obtained from 2, following the synthetic procedure worked out at the Paul Scherrer Institute. Molecular structure of the investigated complex 3 is presented. As it was expected, the ligand coordinates the cation bidentately, via the pyridine nitrogen and the oxygen atoms, and forms a five-membered ring with the metal centre. Stability of 3 towards oxidation was studied in the aerated 0.9% NaCl aqueous solution by registering its UV-Vis spectra as a function of time. Within one week no distinct change in the spectrum was detected. Infrared spectra of the ligand 1 and the complex 3 are shown. All the main bands of the 'fingerprint region' of the pyridinecarboamides (1300 / 700 cm-1) can be found in both spectra. The spectrum of 3 shows the typical pattern for a facial tricarbonyl moiety with bands at 2085, 1998 and 1879 cm-1 (CO ligands vibrations), and a very sharp signal of valency stretching of C=O in the amide group at 1639 cm-1. The far infrared spectrum of 3 reveals six bands which have been interpreted to arise from vibrations of Re-C bonds at 530, 510 and 482 cm-1, Re-N bond at 450 cm-1, Re-O bond at 433 cm-1 and Re-Cl bond at 281 cm-1. The value of partition constant of 3 in the isooctanol - 0.9% NaCl aqueous solution system, log P3 = 0.85 ± 0.09, is greater than the corresponding value for its thio-analogue, log P 0.57 ± 0.15. Further studies on functionalization of 3 with glutathione and/or N-acetyl-cysteine are in progress. Crystallographic data for the structural analysis have been deposited at the Cambridge Crystallographic Data Centre and obtained CCDC No. 270202