The electrochemical profiles of Auranofin andAubipyc, two representative medicinal gold compounds: A comparative study

Monika Prządka-Kupiec , Robert Ziółkowski , L. Massai , L. Messori , Katarzyna Pawlak

Abstract

A micro-electrochemical reaction cell was coupled to an electrospray mass spectrometer in order to track redox transformations for two representative medicinal gold compounds - i.e. [(2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranosato-S)(triethylphosphine)gold(I)] and [Au(bipydmb-H)(OH)][PF6] (where bipydmb-H is deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine), known as Auranofin and Aubipyc respectively - in parallel to square wave voltammetry (SWV) measurements. Irreversible oxidation of thio-glucose tetraacetate was the dominant reaction for the gold(I) compound Auranofin; oxidation was accompanied by hydrolysis leading to progressive deacetylation. Two main active forms were identified for this prodrug: the triethylphosphinegold(I) cation and a gold(I) thioglucose species, with a variable number of acetyl groups. For the gold(III) complex Aubipyc irreversible reduction of the gold(III) center was highlighted, accompanied by a ligand exchange process. The free gold(I) ion is proposed to be the final species that subsequently binds transport proteins in the bloodstream. Molecule specific mass spectrometry determinations provide complementary data to square wave voltammetry helping to understand the nature of the electrochemical conversions of complex or unstable compounds. Finally, it was possible to establish that oxidizing conditions during drug preparation and administration should be avoided in the case of Auranofin; conversely, reduction conditions typical for the blood or the cytosol environment are suitable to obtain the active gold(I) species from the gold(III) complex Aubipyc.
Author Monika Prządka-Kupiec (FC / CAC)
Monika Prządka-Kupiec,,
- Chair Of Analytical Chemistry
, Robert Ziółkowski (FC / CMB)
Robert Ziółkowski,,
- Chair of Medical Biotechnology
, L. Massai - [Universita degli Studi di Firenze]
L. Massai,,
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, L. Messori - [Universita degli Studi di Firenze]
L. Messori,,
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, Katarzyna Pawlak (FC / CAC)
Katarzyna Pawlak,,
- Chair Of Analytical Chemistry
Journal seriesJournal of Inorganic Biochemistry, ISSN 0162-0134, (N/A 70 pkt)
Issue year2019
Vol198
Pages110714-110724
Publication size in sheets0.3
Keywords in English Cytotoxic gold complexes, Metallodrug, Prodrug, Electrochemical cell, Voltammetry, Electrospray MS
ASJC Classification1303 Biochemistry; 1604 Inorganic Chemistry
DOIDOI:10.1016/j.jinorgbio.2019.110714
URL https://www.ncbi.nlm.nih.gov/pubmed/31170580
Languageen angielski
File
wdpb_publikacje_pliki_plik_publikacja_3698_org.pdf 2.06 MB
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 04-02-2020, ArticleFromJournal
Publication indicators Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.895; WoS Impact Factor: 2018 = 3.224 (2) - 2018=3.188 (5)
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