Authors: | Holland, J. P.; Jones, M. W.; Bonnitcha, P. D.; Lewis, J. S.; Dilworth, J. R. |
Article Title: | Functionalised copper-64 complexes as precursors of potential PET imaging agents for neurodegenerative disorders |
Abstract: | A range of unsymmetrical bis(thiosemicarbazonato)zinc(ii) and copper(ii) complexes functionalised with structural features of the neuroactive agents dopamine and tropinone have been synthesised. The new ligands and complexes have been characterised by using mass spectrometry, elemental analysis, NMR, infrared and electronic absorption spectroscopy techniques. Transmetallation reactions of the zinc(ii) analogues with <sup>64</sup>Cu(OAc)<sub>2</sub> in aqueous solution were found to be a rapid and efficient method for preparing <sup>64</sup>Cu-radiolabelled complexes for potential use as in vivo tracers in positron emission tomography (PET). Oxygen-dependent cellular association assays in EMT6 murine carcinoma cells revealed that despite conjugation of the tropinone group and reduced lipophilicity, the bis(thiosemicarbazonato) copper(ii) complex retains hypoxia-selectively in vitro. The results demonstrate that recognised neuroactive pharmacophores can be conjugated to the bis(thiosemicarbazonato)copper(ii) core as potential precursors of <sup>64</sup>Cu-radiopharmaceuticals for imaging of neurodegenerative disorders. © 2009 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. |
Keywords: | controlled study; unclassified drug; nonhuman; positron emission tomography; mass spectrometry; animal cell; mouse; complex formation; oxygen; animal experiment; drug structure; hypoxia; isotope labeling; polymerization; radiopharmaceutical agent; chemical structure; precursor; aqueous solution; nuclear magnetic resonance; dopamine; copper 64; carcinoma cell; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n amino 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)copper; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n amino 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)copper; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)zinc; diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazido] 3 (4 n ethyl 3 thiosemicarbazide); diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazonato] 3 (4 n ethyl 3 thiosemicarbazonato)copper; diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazonato] 3 (4 n ethyl 3 thiosemicarbazonato)zinc; absorption spectroscopy; chemical reaction; degenerative disease; drug conjugation; infrared spectroscopy; lipophilicity; metallation; synthesis |
Journal Title: | New Journal of Chemistry |
Volume: | 33 |
Issue: | 9 |
ISSN: | 1144-0546 |
Publisher: | Royal Society of Chemistry |
Date Published: | 2009-01-01 |
Start Page: | 1845 |
End Page: | 1852 |
Language: | English |
DOI: | 10.1039/b902895a |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Export Date: 30 November 2010" - "CODEN: NJCHE" - "Source: Scopus" |