Metallacages with 2,6-dipicolinoylbis(N,N-dialkylthioureas) as novel platforms in nuclear medicine for 68Ga, 177Lu and 198Au.

BACKGROUND: Heterometallic gold metallacages are of great interest for the incorporation of several cations. Especially in nuclear medicine, those metallacages can serve as a platform for radionuclides relevant for imaging or therapy (e.g. 68Ga or 177Lu). Moreover, the radionuclide 198Au is an attractive beta emitter, for potential application in nuclear medicine. Here, we aim to synthesize a new set of gold metallacages and to study their ability to coordinate to 68Ga, 177Lu and 198Au. RESULTS: New heterometallic gold metallacages of composition [M{Au(Lmorph-κS)}3] (M = La3+, Tb3+, Lu3+ or Y3+) and [Ga{Au(Lmorph-κS)}2]NO3 have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H2Lmorph) with [AuCl(THT)] and the target M3+ metal ions in yields ranging from 33 (Lu) to 62% (Tb). The characterization of the compounds bases on ESI-MS, 1H NMR, IR, EA and single-crystal X-ray diffraction techniques (all except the Ga derivative). Selected gold cages derived from H2Lmorph were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H2Ldiethyl). The tested metallacages show similar IC50 values close to that of auranofin in four different cancer cell lines (MCF-7, PC-3, U383, U343), e.g. 4.5 ± 0.7 µM for [Ga{Au(Ldiethyl)}2]NO3 on PC-3. The radiolabeling experiments thereof show high radiochemical purities with 68Ga and 198Au and low radiochemical purity with 177Lu. CONCLUSIONS: The results indicate that these gold metallacages could serve as a novel platform for inclusion of different (radio)nuclides with potential theranostic applications in nuclear medicine.

Gold-Based Coronands as Hosts for M3+ Metal Ions: Ring Size Matters.

The controlled, self-assembled synthesis of multinuclear coordination compounds can be performed via different approaches. Frequently, steric, geometric and/or electronic factors located at the ligand systems predefine the way in which metal ions can assemble them to large aggregates. For the compounds in the present paper, also the Pearson's acidities and preferred coordination geometries of the metal ions were used as organization principles. The ligand under study, 2,6-dipicolinoylbis(N,N-diethylthiourea), H2L1ethyl, possesses 'soft' sulfur and 'hard' nitrogen and oxygen donors. One-pot reactions of this compound with [AuCl(tht)] (tht = tetrahydrothiophene) and M3+ salts (M = Sc, Y, La, Ln, Ga, In) give products with gold-based {Au3(L1ethyl)3}3+ or {Au2(L1ethyl)2}2+ coronands, which host central M3+ ions. The formation of such units is templated by the M3+ ions and the individual size of the coronand rings is dependent on the ionic radii of the central ions in a way that small ions such as Ga3+ form a [Ga⊂{Au2(L1ethyl)2}]+ assembly, while larger ions (starting from Sc3+/In3+) establish neutral [M⊂{Au3(L1ethyl)3}] units with nine-coordinate central ions.