Article

BioMetals

, Volume 26, Issue 1, pp 85-96

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

  • Rebecca J. SowdenAffiliated withStrathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University
  • , Katherine D. TrotterAffiliated withDepartment of Pure and Applied Chemistry, Strathclyde University
  • , Lynsey DunbarAffiliated withDepartment of Pure and Applied Chemistry, Strathclyde University
  • , Gemma CraigAffiliated withDepartment of Pure and Applied Chemistry, Strathclyde University
  • , Omer ErdemliAffiliated withDepartment of Pure and Applied Chemistry, Strathclyde University
  • , Corinne M. SpickettAffiliated withStrathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde UniversitySchool of Life and Health Sciences, Aston University Email author 
  • , John ReglinskiAffiliated withDepartment of Pure and Applied Chemistry, Strathclyde University

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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