The interaction of silver(II) complexes with biological macromolecules and antioxidants

Katherine D. Trotter, Olawale Owojaiye, Stuart Meredith, Pat E. Keating, Mark D. Spicer, John Reglinski, Corinne M Spickett

Research output: Contribution to journalArticle

Abstract

Silver is widely used for its antimicrobial properties, but microbial resistance to heavy metals is increasing. Silver(II) compounds are more oxidizing and therefore have the potential to overcome resistance via extensive attack on cellular components, but have traditionally been hard to stabilize for biological applications. Here, the high oxidation state cation was stabilised using pyridinecarboxylate ligands, of which the 2,6-dicarboxypyridine Ag(II) complex (Ag2,6P) was found to have the best tractability. This complex was found to be more stable in phosphate buffer than DMSO, allowing studies of its interaction with water soluble antioxidants and biological macromolecules, with the aim of demonstrating its potential to oxidize them, as well as determining the reaction products. Spectrophotometric analysis showed that Ag2,6P was rapidly reduced by the antioxidants glutathione, ascorbic acid and vitamin E; the unsaturated lipids arachidonic and linoleic acids, model carbohydrate β-cyclodextrin, and protein cytochrome c also reacted readily. Analysis of the reaction with glutathione by NMR and electrospray mass spectrometry confirmed that the glutathione was oxidized to the disulfide form. Mass spectrometry also clearly showed the addition of multiple oxygen atoms to the unsaturated fatty acids, suggesting a radical mechanism, and cross-linking of linoleic acid was observed. The seven hydroxyl groups of β-cyclodextrin were found to be completely oxidized to the corresponding carboxylates. Treatment of cytochrome c with Ag2,6P led to protein aggregation and fragmentation, and dose-dependent oxidative damage was demonstrated by oxyblotting. Thus Ag2,6P was found to be highly oxidizing to a wide variety of polar and nonpolar biological molecules.
LanguageEnglish
Pages627-640
Number of pages14
JournalBioMetals
Volume32
Issue number4
Early online date16 May 2019
DOIs
Publication statusPublished - 1 Aug 2019

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Cytochromes c
Antioxidants
Macromolecules
Silver
silver
Glutathione
glutathione
Mass Spectrometry
Silver Compounds
beta-cyclodextrin
cytochrome c
Linoleic Acids
Arachidonic Acids
Proteins
Linoleic acid
antioxidants
Mass spectrometry
Glutathione Disulfide
linoleic acid
Cyclodextrins

Bibliographical note

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Funding: SM and CMS acknowledge BSSRC and Mologic for the Industrial CASE Award BB/J012939/1. CMS and JR acknowledge support from the UK Engineering and Physical Sciences Research Council (EPSRC) funded “Aston Multidisciplinary Research for Antimicrobial Resistance: The AMR4AMR project” grant, EP/M02735X/1.

Keywords

  • Ag(II) 2,6-dicarboxypyridine
  • Antimicrobial metal
  • Glutathione
  • Lipid peroxidation
  • Oxidative stress

Cite this

Trotter, K. D., Owojaiye, O., Meredith, S., Keating, P. E., Spicer, M. D., Reglinski, J., & Spickett, C. M. (2019). The interaction of silver(II) complexes with biological macromolecules and antioxidants. BioMetals, 32(4), 627-640. https://doi.org/10.1007/s10534-019-00198-0
Trotter, Katherine D. ; Owojaiye, Olawale ; Meredith, Stuart ; Keating, Pat E. ; Spicer, Mark D. ; Reglinski, John ; Spickett, Corinne M. / The interaction of silver(II) complexes with biological macromolecules and antioxidants. In: BioMetals. 2019 ; Vol. 32, No. 4. pp. 627-640.
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Trotter, KD, Owojaiye, O, Meredith, S, Keating, PE, Spicer, MD, Reglinski, J & Spickett, CM 2019, 'The interaction of silver(II) complexes with biological macromolecules and antioxidants' BioMetals, vol. 32, no. 4, pp. 627-640. https://doi.org/10.1007/s10534-019-00198-0

The interaction of silver(II) complexes with biological macromolecules and antioxidants. / Trotter, Katherine D.; Owojaiye, Olawale; Meredith, Stuart; Keating, Pat E.; Spicer, Mark D.; Reglinski, John; Spickett, Corinne M.

In: BioMetals, Vol. 32, No. 4, 01.08.2019, p. 627-640.

Research output: Contribution to journalArticle

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Trotter KD, Owojaiye O, Meredith S, Keating PE, Spicer MD, Reglinski J et al. The interaction of silver(II) complexes with biological macromolecules and antioxidants. BioMetals. 2019 Aug 1;32(4):627-640. https://doi.org/10.1007/s10534-019-00198-0