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Abstract
The application of Au(I) ions in pharmaceuticals, including in nuclear medicine, is limited by their instability towards reduction in vivo. The gold radionuclide 198Au with a half-life of 2.7 days emits gamma radiation ideal for diagnostic purposes and also generates β- particles suitable for effective cancer radiotherapy, making it a perfect nuclide for ‘theranostics’. Here, we explore N-heterocyclic carbene (NHC) organometallic chemistry to stabilize 198Au(I) in radiopharmaceuticals. Thus, different Au(I) NHC compounds featuring different scaffolds have been selected for 198Au radiolabeling. Two new benzimidazol-2-ylidene Au(I) complexes bearing peptide ligands enabling blood brain barrier translocation in vitro have also been synthesized and their radiolabeling attempted. The obtained proof-of-concept results showed that NHCs are suitable ligands to achieve isotope exchange in Au(I) complexes, with imidazole derivatives being particularly stable, also in the presence of AuCl(THT) and human serum albumin. Overall, our work reveals the still untapped potential of organometallic chemistry in radiopharmaceutical design.
Supplementary materials
Title
supplementary information
Description
Figure S1 – 1H NMR of AuNHC-2 in DMF-d7.
Figure S2 – 13C NMR of AuNHC-2 in DMF-d7.
Figure S3 – HR-ESI-MS of AuNHC-2: the inset shows the isotopic pattern of the species [M+] (m/Z 633.1749, mass error = -4.1 ppm.)
Figure S4 - UV-chromatogram of AuTMX2.
Figure S5 - UV-chromatogram of AuNHC-1.
Figure S6 - UV-chromatogram of AuNHC-2.
Figure S7 - UV-chromatogram of AuNHC-2-pep.
Figure S8 – HR-DESI-MS of AuNHC-2-pep: the inset shows the isotopic pattern of the species [M+2H]2+ (m/Z 728.8509, mass error = 0.0 ppm).
Figure S9 - UV-chromatogram of AuNHC-2-pep2.
Figure S10 – ESI-MS of AuNHC-2-pep2.
Figure S11 – Cytotoxicity studies.
Figure S12 – Radio-HPLC chromatogram of [198Au]AuNHC-1 in human serum albumin after precipitation of proteins.
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