BioMetals

, Volume 26, Issue 1, pp 85–96 | Cite as

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing

  • Rebecca J. Sowden
  • Katherine D. Trotter
  • Lynsey Dunbar
  • Gemma Craig
  • Omer Erdemli
  • Corinne M. Spickett
  • John Reglinski
Article

Abstract

A series of simple copper N2S2 macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Keywords

Copper macrocycles Oxidation–reduction Glutathione Ascorbate Vitamin E Oxidative stress 

Abbreviations

cis-H4NenSen

5,6,13,14-Bisbenzo-8,11-diaza-1,4-dithia-cyclotetradecane

cis-H4NprSen

5,6,14,15-Bisbenzo-8,12-diaza-1,4-dithia-cyclopentadecane

cis-H4NenSpr

6,7,14,15-Bisbenzo-9,12-diaza-1,5-dithia-cyclopentadecane

cis-H4NprSpr

6,7,15,16-Bisbenzo-9,13-diaza-1,5-dithia-cyclohexadecane

trans-H4(N-en-S)2

6,7,13,14-Bisbenzo-4,11-diaza-1,8-dithiacyclotetradecane

cis-H2Nen(CH2CH2OH)2Spr

6,7,14,15-Bisbenzo-9,12,-diaza-1,5-dithiacyclopentadecine-9,12-diethanol

Notes

Acknowledgments

KDT would like to thank Strathclyde University and WestChem for financial assistance. JR, CMS and RJS gratefully acknowledge the support of the BBSRC (BBS/B/01553) and would also like to thank Prof. Peter J Halling for helpful discussion.

Supplementary material

10534_2012_9596_MOESM1_ESM.ppt (206 kb)
Supplementary material 1 (PPT 206 kb)

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Rebecca J. Sowden
    • 1
  • Katherine D. Trotter
    • 2
  • Lynsey Dunbar
    • 2
  • Gemma Craig
    • 2
  • Omer Erdemli
    • 2
  • Corinne M. Spickett
    • 1
    • 3
  • John Reglinski
    • 2
  1. 1.Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde UniversityGlasgowUK
  2. 2.Department of Pure and Applied ChemistryStrathclyde UniversityGlasgowUK
  3. 3.School of Life and Health Sciences, Aston UniversityBirminghamUK

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