JBIC Journal of Biological Inorganic Chemistry

, 13:861

Cellular uptake and distribution of cobalt complexes of fluorescent ligands

  • Natsuho Yamamoto
  • Sarah Danos
  • Paul D. Bonnitcha
  • Timothy W. Failes
  • Elizabeth J. New
  • Trevor W. Hambley
Original Paper

DOI: 10.1007/s00775-008-0374-7

Cite this article as:
Yamamoto, N., Danos, S., Bonnitcha, P.D. et al. J Biol Inorg Chem (2008) 13: 861. doi:10.1007/s00775-008-0374-7

Abstract

The development of complexes that allow the monitoring of the release and distribution of fluorescent models of anticancer drugs initially bound to cobalt(III) moieties is reported. Strong quenching of fluorescence upon ligation to cobalt(III) was observed for both the carboxylate- and the hydroximate-bound fluorophores as was the partial return of fluorescence following addition of ascorbate and cysteine. The extent of the increase in the fluorescence intensity observed following addition of these potential reductants is indicative of the fluorophore being displaced from the complex by the action of ascorbate or cysteine, by ligand exchange. The cellular distribution of the fluorescence revealed that coordination to cobalt can dramatically alter the subcellular distribution of a bound fluorophore. This work shows that fluorescence can be an effective means of monitoring these agents in cells, and of determining their sites of activation. The results also reveal that the cytotoxicity of such agents correlates with their uptake and distribution patterns and that these are influenced by the types of ligands attached to the complex.

Keywords

Anticancer drugImaging

Abbreviations

ahaH2

Acetohydroxamic acid

c343H

Coumarin-343

c343haH2

Coumarin-343 hydroxamic acid

cyclam

1,4,8,11-Tetraazacyclotetradecane

DMF

N,N′-dimethylformamide

DMSO

Dimethyl sulfoxide

ESI

Electrospray ionisation

HPLC

High-performance liquid chromatography

MTT

3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide

tpa

Tris(2-methylpyridine)amine

Supplementary material

775_2008_374_MOESM1_ESM.pdf (467 kb)
Supplementary material (PDF 466 kb).

Copyright information

© SBIC 2008

Authors and Affiliations

  • Natsuho Yamamoto
    • 1
  • Sarah Danos
    • 1
  • Paul D. Bonnitcha
    • 1
  • Timothy W. Failes
    • 1
  • Elizabeth J. New
    • 1
  • Trevor W. Hambley
    • 1
  1. 1.Centre for Heavy Metals Research, School of ChemistryThe University of SydneySydneyAustralia