The facile and additive-free synthesis of a cell-friendly iron()-glutathione complex

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 49; no. 3; pp. 1574 - 1579
• Main Authors: Gao, Ziyu, Carames-Mendez, Pablo, Xia, Dong, Pask, Christopher M, McGowan, Patrick C, Bingham, Paul A, Scrimshire, Alex, Tronci, Giuseppe, Thornton, Paul D
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 04.08.2020
• Subjects: Aqueous solutions; Cell culture; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Ferric Compounds - chemistry; Ferric Compounds - pharmacology; Fluorescence; Glutathione; Glutathione - chemistry; Glutathione - pharmacology; Growth factors; Humans; Iron; Mass spectrometry; Matrix Metalloproteinase 13 - metabolism; Matrix metalloproteinases; Molecular Structure; Sodium sulfide; Statistical analysis; X ray photoelectron spectroscopy; X ray powder diffraction
• ISSN: 1477-9226; 1477-9234; 1477-9234
• DOI: 10.1039/d0dt02331k

The straightfoward creation of an unreported glutathione-stabilised iron( iii ) complex is disclosed. In contrast to previous reports, glutathione was shown to coordinate and stabilise iron directly under physiological conditions in the absence of additional sulfur containing molecules, such as sodium sulfide. The complex was extensively characterised; the molecular geometry was determined as two inequivalent octahedra, approximately 2/3 of which are slightly distorted towards more tetrahedral in character, with the remaining 1/3 more regularly octahedral. The dispersion of the iron( iii )-glutathione complex in aqueous solution yielded particles of 255 ± 4 nm in diameter that enhanced the growth and proliferation of L929 fibroblast cells over 7 days, and inhibited the activity of matrix metalloproteinase-13. Consequently, the unprecedented glutathione-stabilised iron( iii ) complex disclosed has potential use as a simple-to-prepare growth factor for inclusion within cell culture media, and is an excellent candidate as a therapeutic for the treatment of metalloproteinase-13-associated diseases. The straightforward creation of an unreported glutathione-stabilised iron( iii ) complex that enhances L929 fibroblast cell viability, and inhibits matrix metalloproteinase-13 activity is described.