Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics. (16th June 2021)

• Record Type: Journal Article
• Authors: Gilpin, Ian Moore F.; Ullrich, Martin; Wünsche, Thomas; Zarschler, Kristof; Lebeda, Ondřej; Pietzsch, Jens; Pietzsch, Hans‐Jürgen; Walther, Martin
• Is Part Of: ChemMedChem. Volume 16:Number 17(2021)
• Page Start: 2645
• Page End: 2649
• Publication Date: 2021-06-16
• Subjects: Bispidine -- Mercury -- Organomercury -- Radiopharmaceuticals -- Theranostics; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100131
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg−Ph to Hg−S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg−R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in 197(m) HgCl2 (aq), so the desired mercury compound was formed via a water‐tolerant organotin transmetallation. The Hg‐bispidine compound showed high chemical stability in tests with an excess of sulfur‐containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The nat Hg analogue allowed full characterization by NMR and HRMS. Abstract : Stable and versatile : The cyclic bisarylmercury bispidine structure shows exceptional stability against sulfur compounds known to usually react very easily with mercury. Aside from its novelty in mercury chemistry, the in vivo stability paired with the functionalizability of this motif is an important step forward in the development of useful radiomercury pharmaceuticals.