First-generation bispidine chelators for 213BiIII radiopharmaceutical applications
Hepta- and octadentate bispidines (3,7-diazabicyclo[3.3.1]nonane, diaza-adamantane) with acetate, methyl-pyridine, and methyl-picolinate pendant groups at the amine donors of the bispidine platform have been prepared and used to investigate BiIII coordination chemistry. Crystal structure and solutio...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2020
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| In: |
ChemMedChem
Year: 2020, Volume: 15, Issue: 16, Pages: 1591-1600 |
| ISSN: | 1860-7187 |
| DOI: | 10.1002/cmdc.202000361 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/cmdc.202000361 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000361 
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| Author Notes: | Frank Bruchertseifer, Peter Comba, Bodo Martin, Alfred Morgenstern, Johannes Notni, Miriam Starke, and Hubert Wadepohl |
| Summary: | Hepta- and octadentate bispidines (3,7-diazabicyclo[3.3.1]nonane, diaza-adamantane) with acetate, methyl-pyridine, and methyl-picolinate pendant groups at the amine donors of the bispidine platform have been prepared and used to investigate BiIII coordination chemistry. Crystal structure and solution spectroscopic data (NMR spectroscopy and mass spectrometry) confirm that the rigid and relatively large bispidine cavity with an axially distorted geometry is well suited for BiIII and in all cases forms nine-coordinate complexes; this is supported by an established hole size and shape analysis. It follows that nonadentate bispidines probably will be more suited as bifunctional chelators for 213BiIII-based radiopharmaceuticals. However, two isomeric picolinate-/acetate-based heptadentate ligands already show very efficient complexation kinetics with 213BiIII at ambient temperature and kinetic stability that is comparable with the standard ligands used in this field. The experimentally determined hydrophilicities (log D7.4 values) show that the BiIII complexes reported are relatively hydrophilic and well suited for medicinal applications. We also present a very efficient and relatively accurate method to compute charge distributions and hydrophilicities, and this will help to further optimize the systems reported here. |
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| Item Description: | First published: 02 July 2020 Im Titel ist 213 und III bei "Bi" hochgestellt Gesehen am 05.11.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1860-7187 |
| DOI: | 10.1002/cmdc.202000361 |