Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics
| Autor: | Martin Ullrich, Martin Walther, Hans-Jürgen Pietzsch, Kristof Zarschler, Ian Moore F. Gilpin, Thomas Wünsche, Jens Pietzsch, Ondřej Lebeda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
chemistry.chemical_element 01 natural sciences Biochemistry Bispidine Organomercury Theranostic Nanomedicine chemistry.chemical_compound Transmetalation Drug Stability In vivo Drug Discovery Organometallic Compounds Humans General Pharmacology Toxicology and Pharmaceutics Pharmacology Mercury Radioisotopes 010405 organic chemistry Communication Organic Chemistry Mercury Theranostics Combinatorial chemistry Bond-dissociation energy Communications 0104 chemical sciences Mercury (element) 010404 medicinal & biomolecular chemistry chemistry Molecular Medicine Surface modification Chemical stability Radiopharmaceuticals |
| Zdroj: | Chemmedchem |
| ISSN: | 1860-7187 1860-7179 |
| Popis: | 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 natHg analogue allowed full characterization by NMR and HRMS. 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. |
| Databáze: | OpenAIRE |
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