Copper and zinc bis(thiosemicarbazonato) complexes with a fluorescent tag: synthesis, radiolabelling with copper-64, cell uptake and fluorescence studies.
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 (64)Cu 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.
Lim
SinChun
S
School of Chemistry, University of Melbourne, Parkville, VIC, 3010, Australia.
Price
Katherine A
KA
Chong
Siow-Feng
SF
Paterson
Brett M
BM
Caragounis
Aphrodite
A
Barnham
Kevin J
KJ
Crouch
Peter J
PJ
Peach
Josephine M
JM
Dilworth
Jonathan R
JR
White
Anthony R
AR
Donnelly
Paul S
PS
D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D003300:Copper / Q000737:chemistry*; D003301:Copper Radioisotopes / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011721:Pyrenes / Q000737:chemistry; D013882:Thiosemicarbazones / Q000737:chemistry*; D014018:Tissue Distribution; D015032:Zinc / Q000737:chemistry*
D003301:Copper Radioisotopes; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D011721:Pyrenes; D013882:Thiosemicarbazones; D003300:Copper; D015032:Zinc