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.

Functionalized bis(thiosemicarbazonato) complexes of zinc and copper: synthetic platforms toward site-specific radiopharmaceuticals.

Two new types of unsymmetrical bis(thiosemicarbazone) proligands and their neutral zinc(II) and copper(II) complexes have been synthesized. These bifunctional ligands both chelate the metal ions and provide pendent amino groups that can be readily functionalized with biologically active molecules. Functionalization has been demonstrated by the synthesis of three water-soluble glucose conjugates of the new zinc(II) bis(thiosemicarbazonato) complexes, and their copper(II) analogues have been prepared in aqueous solution via transmetalation. A range of techniques including NMR, electron paramagnetic resonance, cyclic voltammetry, high-performance liquid chromatography (HPLC), UV/vis, and fluorescence emission spectroscopy have been used to characterize the complexes. Four compounds, including two zinc(II) complexes, have been characterized by X-ray crystallography. The connectivity and conformation of the glucose conjugates have been assigned by NMR spectroscopy. Time-dependent density functional theory calculations have been used to assign the electronic transitions of the copper(II) bis(thiosemicarbazonato) chromophore. Two copper-64-radiolabeled complexes, including one glucose conjugate, have been prepared and characterized using radio-HPLC, and transmetalation is shown to be a viable method for radiolabeling compounds with copper radionuclides. Preliminary cell washout studies have been performed under normoxic conditions, and the uptake and intracellular distribution have been studied using confocal fluorescence microscopy.

Fluorescence studies of the intra-cellular distribution of zinc bis(thiosemicarbazone) complexes in human cancer cells.

The uptake of zinc bis(thiosemicarbazone) complexes in human cancer cells has been studied by fluorescence microscopy and the cellular distribution established, including the degree of uptake in the nucleus.

Approximate quantum cloning with nuclear magnetic resonance.

Here we describe a nuclear magnetic resonance (NMR) experiment that uses a three qubit NMR device to implement the one-to-two approximate quantum cloning network of Buzek et al. [Phys. Rev. A 56, 3446 (1997)]. As expected the experimental results indicate that the network clones all input states with similar fidelities, but as a result of decoherence and incoherent evolution arising from B(1) inhomogeneity the total fidelity achieved does not exceed the measurement bound.