JBIC Journal of Biological Inorganic Chemistry

, Volume 15, Issue 2, pp 225–235

Copper and zinc bis(thiosemicarbazonato) complexes with a fluorescent tag: synthesis, radiolabelling with copper-64, cell uptake and fluorescence studies

  • SinChun Lim
  • Katherine A. Price
  • Siow-Feng Chong
  • Brett M. Paterson
  • Aphrodite Caragounis
  • Kevin J. Barnham
  • Peter J. Crouch
  • Josephine M. Peach
  • Jonathan R. Dilworth
  • Anthony R. White
  • Paul S. Donnelly
Original Paper

DOI: 10.1007/s00775-009-0587-4

Cite this article as:
Lim, S., Price, K.A., Chong, SF. et al. J Biol Inorg Chem (2010) 15: 225. doi:10.1007/s00775-009-0587-4

Abstract

The synthesis of new copper(II) bis(thiosemicarbazonato) complexes with an appended pyrene chromophore and their zinc(II) analogues is reported. The new proligands and their copper(II) and zinc(II) complexes were characterised by a combination of NMR, EPR, high performance liquid chromatography, mass spectrometry, electronic spectroscopy and electrochemical measurements. The new copper(II) complexes are fluorescent as a consequence of an appended pyrene substituent that is separated from the sulphur coordinating to the metal ion by five bonds. The emission from the pyrene substituent is concentration- and solvent-dependent with characteristic formation of excimer aggregates. A radioactive 64Cu complex has been prepared. Cell permeability, intracellular distribution and importantly the ability to cross the nuclear membrane to target DNA were investigated using confocal fluorescence microscopy in a human cancer cell line under normal oxygen conditions and hypoxic conditions. In both cases, there was no evidence of uptake of the copper(II) bis(thiosemicarbazonato) complexes in the area of the cell nucleus.

Keywords

Coordination chemistry Fluorescence Synthesis Copper(II) bis(thiosemicarbazone) Copper radiopharmaceuticals 

Abbreviations

H2atse/a

Diacetyl bis(N4-ethyl-N4′-amino-thiosemicarbazone)

H2atsm

Diacetyl bis(N4-methylthiosemacarbazone)

H2atsm/a

Diacetyl bis(N4-methyl-N4′-amino-thiosemicarbazone)

CuII(atsm)

Diacetyl bis(N4-methylthiosemicarbazonato)copper(II)

CuII(gtsm)

Glyoxalbis(N4-methylthiosemicarbazonato)copper(II)

DMF

Dimethylformamide

d6-DMSO

Deuterated dimethyl sulphoxide

DMSO

Dimethyl sulphoxide

EPR

Electron paramagnetic resonance

ES-MS

Electrospray mass spectrometry

ICP-MS

Inductively coupled plasma mass spectrometry

LR

LysoTracker Red

PB

Phosphate buffer

SCE

Saturated calomel electrode

Supplementary material

775_2009_587_MOESM1_ESM.pdf (105 kb)
Supplementary material 1 (PDF 105 kb)

Copyright information

© SBIC 2009

Authors and Affiliations

  • SinChun Lim
    • 1
    • 2
  • Katherine A. Price
    • 3
  • Siow-Feng Chong
    • 1
    • 2
  • Brett M. Paterson
    • 1
    • 2
  • Aphrodite Caragounis
    • 3
  • Kevin J. Barnham
    • 2
    • 3
  • Peter J. Crouch
    • 3
  • Josephine M. Peach
    • 4
  • Jonathan R. Dilworth
    • 4
  • Anthony R. White
    • 3
  • Paul S. Donnelly
    • 1
    • 2
  1. 1.School of ChemistryUniversity of MelbourneParkvilleAustralia
  2. 2.Bio21 Molecular Science and Biotechnology InstituteUniversity of MelbourneMelbourneAustralia
  3. 3.Department of PathologyUniversity of MelbourneMelbourneAustralia
  4. 4.Chemistry Research Laboratory, Department of ChemistryUniversity of OxfordOxfordUK

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