Tricarbonyltechnetium(I) and tricarbonylrhenium(I) complexed with N-methyl-2-pyridinecarboxyamide as potential radiopharmaceuticals: a computational study

Abstract

The electronic and thermodynamic properties of the '2 ? 1' tricarbonyltechnetium(I) and -rhenium(I) mixed ligand complexes with N-methylpyridine-2-carboxyamide (MPCA) as a bidentate ligand and chloride, water, or tert-butyl-3-isocyanopropanoate (BCP), were investigated within the framework of Density Functional Theory. The atomic charges of all complexes, polarization of the CO groups, as well as the effect of transfer of p-electron density between the ligands through the metal were calculated and compared. The free energies of the reaction of formation of the isocyanide complexes in aqueous solution were calculated based on calculated total free energies in aqueous solution of the products and the substrates. The dissociation energies of the complexes were also determined in order to rationalize the experimentally observed higher resistance of the rhenium compared to the technetium complexes in the challenge experiments with the standard sulfur-containing amino acids.

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?

“…1 H NMR spectrum (CDCl 3 , δ, ppm; the atom numbering is the same as in Figure ): 8.855 d (2H, H bipy4,13 , 3 J 6.0 Hz), 8.59 d (2H, H bipy7,10 , 3 J 8.0 Hz), 8.34 t (2H, H bipy5,12 , 3 J 6.0 Hz), 7.65 t (2H, H bipy6,11 , 3 J 6.0 Hz), 4.48 s (2H, CN–C H 2 –COO−), 4.20 q (2H, C H 2 –CH 3 , 3 J 8.0 Hz), 1.25 t (3H, –C H 3 , 3 J 8.0 Hz). 13 C­{ 1 H} NMR spectrum (CDCl 3 , δ, ppm): 163.2 (1C, –COO−), 155.3 (2C, bipy , ), 153.0 (2C, bipy , ), 140.6 (2C, bipy , ), 127.4 (2C, bipy , ), 125.1 (2C, bipy , ), 63.2 (1C, –O– C H 2 –CH 3 ), 46.2 (1C, CN– C H 2 –COO−), 13.9 (1C, –O–CH 2 – C H 3 ). Calculated for [C 18 H 15 N 3 O 5 Tc]­(ClO 4 ), %: C 39.25, H 2.75, N 7.63, 99 Tc 17.79.…”

“…Among monodentate ligands for implementing the 2 + 1 B approach (tethering of a biomolecule via monodentate ligand), isonitriles seem to be the best choice , owing to the favorable combination of σ-donor and π-acceptor properties (ensuring high stability of the complexes), low steric demand, good complexation kinetics, and versatility in linking to biomolecules. For example, complexes with ω-isonitrile-derivatized higher fatty acids , show promise for myocardial imaging, whereas isonitrile-derivatized lower fatty acids can serve as bifunctional molecules for tethering the 99m Tc­(CO) 3 + core to diverse biomolecules. , Isonitriles as ligands for the 99m Tc­(CO) 3 + core have been examined in combination with diverse bidentate ligands. ,,− As a rule, anionic bidentate ligands were chosen. It is believed that, with neutral bidentate ligands, the sixth coordination site in the tricarbonyl complexes will be occupied by the chloride ion necessarily present in the reaction medium, and its replacement by a monodentate ligand will be hindered.…”

“…8.855 d (2H, H bipy4,13 , 3 J 6.0 Hz), 8.59 d (2H, H bipy7,10 , 3 J 8.0 Hz), 8.34 t (2H, H bipy5,12 , 3 J 6.0 Hz), 7.65 t (2H, H bipy6,11 , 3 J 6.0 Hz), 4.48 s (2H, CN− CH 2 −COO−), 4.20 q (2H, CH 2 −CH 3 , 3 J 8.0 Hz), 1.25 t (3H, −CH 3 , 3 J 8.0 Hz) 13. C{ 1 H} NMR spectrum (CDCl 3 , δ, ppm): 163.2 (1C, −COO−), 155.3 (2C, bipy8,9 ), 153.0 (2C, bipy4,13 ), 140.6 (2C, bipy6,11 ), 127.4 (2C, bipy5,12 ), 125.1 https://doi.org/10.1021/acs.inorgchem.3c02204 Inorg. Chem.…”

Interplay of thermochemistry and Structural Chemistry, the journal (volume 21, 2010) and the discipline

“…Using DFT, Fuks et al [211] proved that in vitro behavior of tricarbonylrhenium(I) and tricarbonyltechnetium(I) complexed by the N-methyl-2-pyridinecarboxyamide and chloride, water or tert-butyl-3-isocyanopropionate is thermodynamically controlled. The energy of formation of the complexes containing tertbutyl-3-isocyanopropanoate ligand is more negative by a few kcal mol -1 than energy of those having a coordinated water molecules instead.…”