New metal complexes supported by scorpionate and macrocyclic ligands: chemistry and biological studies

I and my research group have focused our attention on the study of the coordinative ability of monoanionic heteroscorpionate ligands based on bis(pyrazol-1-yl)methanes containing acetate or sulfonate groups as the third coordinating moiety in particular toward rhenium. The similarity between technetium and rhenium chemistry, in fact, determined a widespread use of the latter as a technetium surrogate to perform macroscopic chemistry of potential radiopharmaceuticals. In this way, a ‘‘cold'' material (the natural isotopic mixture of 185Re and 187Re) can be advantageously manipulated instead of the radioactive nuclide 99gTc (t1/2 = 2.12 105 y, Ea'¢ = 292 keV). On the other hand, rhenium has two a'¢- emitters isotopes 186Re (a'¢-max = 1.07 max = 2.10 MeV; t1/2 = 17 h) which are of great interest to nuclear medicine due to their physical and nuclear properties finalized to a potential application in the radiopharmaceutical. For this reason, a renewed interest in rhenium coordination chemistry fluourished, finalized to a potential application in the radiopharmaceutical field of rhenium itself, which was no longer considered as a mere technetium substitute for chemical investigations at macroscopic level. In the past few years the so-called ‘‘metal fragment'' strategy for the synthesis of new technetium and rhenium radiopharmaceuticals revealed to be a promising approach. This methodology is based on the preparation of intermediate species comprising a stable building- block constituted by the metal and suitable ancillary ligands and labile modentate groups (e.g., water molecules or halide groups), which can be easily replaced by chelating bi- or tri-dentate ligands eventually conjugated to a specific biomolecule. According to this strategy, we have reported on a new class of compounds containing the stable metal fragment [Re(O)(NNO)]2+ (N,N,O = tripodal heteroscorpionate ligand). In fact, in order to stabilize the monooxo rhenium core, heteroscorpionate ligands were chosen due to their coordinative flexibility and proper (facial) stereochemical arrangement. In particular, monoanionic bis(pyrazol-1-yl)methane derivatives, containing acetate (Hbpza = bis(pyrazol-1-yl)acetate; Libdmpza = Lithium[Bis(3,5-dimethylpyrazol-1-yl)acetate]) or sulfonate groups (Libdmpzs = Lithium[Bis(3,5-dimethylpyrazol-1-yl)methanesulfonate]), by reaction with [NBu4][Re(O)Cl4], gave a series of intermediate compounds Re(O)(NNO)Cl(X), where the octahedral coordination sphere is filled with two modentate groups (X = Cl or OR) whose structure depends on the type of NNO ligand and solvent utilized. Besides, we have seen that the effectiveness of replacement of two modentate groups of intermediate species with a bidentate chelate (ethylene glycol, malonic acid and 1,3-propandiol) depends on the nature of the heteroscorpionate, and that the substitution takes place easily when N,N,O ligand bear methylated pyrazolyl rings