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

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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
-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 crosslinking
of linoleic acid was observed. The seven hydroxyl groups of -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.

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  • interaction of silver(II)

    Rights statement: Copyright: 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.

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Details

Original languageEnglish
JournalBioMetals
Early online date16 May 2019
DOIs
Publication statusE-pub ahead of print - 16 May 2019

Bibliographic note

Copyright: 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

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