A crystallographic and mechanistic study of Mn triad complexes as model radiopharmaceuticals

Abstract

A series of fac-manganese(I) tricarbonyl complexes were synthesized and analysed to better understand the chemical properties of the group 7 radiopharmaceutical model complex. Five new complexes containing N,O’, N,N’,O and O,O’ donating functionalities were successfully synthesized. The Schiff base ligands, SalH-mTol = 2-(m-tolyliminomethyl)phenol, SalH-cyHex = 2-(Cyclohexyliminomethyl)phenol and 5Me-SalH-Hist = 2-(2-imidazol-4-yl)ethyliminomethyl-5-methylphenol are derived from a salicylidene backbone. The O,O’ are the β-diketone ligands (acetylacetone= AcacH and trifluoroacetylacetone = TfacacH). The ligands were strategically selected to ensure systematic variation in electronic and steric effects. The synthesis of complexes fac-[Mn(Sal-mTol)(CO)3]2, fac-[Mn(Sal-CyHex)(CO)3]2, fac-[Mn(4-Me-Sal-Hist)(CO)2], fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] is reported and all the complexes were characterised by IR, NMR, UV-Vis and single crystal X-Ray diffraction to better understand the solid and solution state. All complexes afford an octahedral environment around the metal centre with the chelating ligands and three carbonyl ligands in facial arrangement. The octahedron is satisfied by a bridging oxygen atom in the dimeric complexes fac-[Mn(Sal-mTol)(CO)3]2 and fac-[Mn(Sal-CyHex)(CO)3]2, and a methanol molecule in complexes fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] Substitution kinetics of the coordinated methanol molecule in complexes fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] by a neutral imidazole ligand was evaluated. The negative values obtained for the activation entropy parameter, Δ𝑆��≠ [-88(1) J K-1 mol-1 and -18(6) J K-1 mol-1], in both complexes is suggestive of an associative type mechanism. As anticipated, the overall rate of methanol substitution in complex fac-[Mn(Acac)(CO)3](OHCH3)] is faster than in fac-[Mn(Tfacac)(CO)3(OHCH3)] as indicated by the overall larger k1 and K1, due to the presence of electron withdrawing fluorine atoms on the ligand backbone.