The electrochemical profiles of Auranofin and Aubipyc, two representative medicinal gold compounds: A comparative study.

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.

journal_name

J Inorg Biochem

authors

Kupiec M,Ziółkowski R,Massai L,Messori L,Pawlak K

doi

10.1016/j.jinorgbio.2019.110714

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

110714

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(18)30710-4

journal_volume

198

pub_type

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