Near-UV and Visible Light Degradation of Iron (III)-Containing Citrate Buffer: Formation of Carbon Dioxide Radical Anion via Fragmentation of a Sterically Hindered Alkoxyl Radical.
Mol Pharm
; 19(11): 4026-4042, 2022 11 07.
Article
em En
| MEDLINE
| ID: mdl-36074094
ABSTRACT
Citrate is a commonly used buffer in pharmaceutical formulations which forms complexes with adventitious metals such as Fe3+. Fe3+-citrate complexes can act as potent photosensitizers under near-UV and visible light exposure, and recent studies reported evidence for the photo-production of a powerful reductant, carbon dioxide radical anion (â¢CO2-), from Fe3+-citrate complexes (Subelzu, N.; Schöneich, N., Mol. Pharm. 2020, 17, 4163-4179). The mechanisms of â¢CO2- formation are currently unknown but must be established to devise strategies against â¢CO2- formation in pharmaceutical formulations which rely on the use of citrate buffer. In this study, we first established complementary evidence for the photolytic generation of â¢CO2- from Fe3+-citrate through spin trapping and electron paramagnetic resonance (EPR) spectroscopy, and subsequently used spin trapping in conjunction with tandem mass spectrometry (MS/MS) for mechanistic studies on the pathways of â¢CO2- formation. Experiments with stable isotope-labeled citrate suggest that the central carboxylate group of citrate is the major source of â¢CO2-. Competition studies with various inhibitors (alcohols and dimethyl sulfoxide) reveal two mechanisms of â¢CO2- formation, where one pathway involves ß-cleavage of a sterically hindered alkoxyl radical generated from the hydroxyl group of citrate.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dióxido de Carbono
/
Ferro
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article