title: Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.
abstract: A series of simple copper N(2)S(2) 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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, 27 Taylor Street, Glasgow, G4 0NR, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Sowden
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Trotter
authors.forename: Lynsey
authors.initials: L
authors.lastname: Dunbar
authors.forename: Gemma
authors.initials: G
authors.lastname: Craig
authors.forename: Omer
authors.initials: O
authors.lastname: Erdemli
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spickett
authors.forename: John
authors.initials: J
authors.lastname: Reglinski
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004492:Edetic Acid / Q000737:chemistry; D004988:Ethers, Cyclic / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D006997:Hypochlorous Acid / Q000737:chemistry*; D008970:Molecular Weight; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D019163:Reducing Agents / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012973:Sodium Hypochlorite / Q000737:chemistry; D012996:Solutions; D013440:Sulfides / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D056831:Coordination Complexes; D004988:Ethers, Cyclic; D016877:Oxidants; D019163:Reducing Agents; D012996:Solutions; D013440:Sulfides; D014810:Vitamin E; D012710:Serum Albumin, Bovine; D006997:Hypochlorous Acid; D003300:Copper; D004492:Edetic Acid; D012973:Sodium Hypochlorite; D005978:Glutathione; D001205:Ascorbic Acid