Synthesis and characterization of neutral technetium(III)-99 and -99m complexes with O,P-bidentate phosphino-carboxylate ligands. Crystal structure of mer-[Tc(O2CCH2CH2PPh2)3]·2Me2SO

Abstract

Reduction–substitution reactions of pertechnetate with a class of O,P-bidentate phosphinocarboxylic acid ligands HLⁿ[n= 1,2-(diphenylphosphino)benzoic acid; n= 2, 3-(diphenylphosphino)propionic acid; n= 3, (diphenylphosphino)acetic acid; n= 4, 3-(diethylphosphino)propionic acid] afforded a series of neutral and paramagnetic [TcLⁿ₃] complexes. The products have been characterized by means of elemental analysis, IR, ¹H NMR, UV/VIS and FAB mass spectroscopy, and X-ray crystallography for [TcL²₃]. The latter crystallizes in the monoclinic space group P2₁/n with Z= 4, a= 21.718(10), b= 12.954(6), c= 18.038(9)Å and β= 106.59(4)°. The final R value was 0.061. Three deprotonated chelates surround the metal in a distorted-octahedral environment adopting a meridional configuration, and consequently there are two pairs of like donor atoms trans to one another with the remaining phosphorus atom trans to an oxygen atom. Similar reduction–substitution reactions have been performed utilizing the short-lived isotope ^99mTc. The physicochemical properties of the resulting ^99mTc-labelled species match very well those exhibited by the analogues prepared with the long-lived isotope ⁹⁹Tc. Thus the chemical structures of [^99mTcLⁿ₃] and [⁹⁹TcLⁿ₃] analogues are identical. Female Sprague–Dawley rats were injected with pre-purified [^99mTcLⁿ₃](n= 1, 2 or 4) and the resulting biodistributions evaluated at different times post injection. All the complexes undergo very low, but significant, brain uptake which decreases with time.