Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake

Squarcina A, Franke A, Senft L, Onderka C, Langer J, Vignane T, Filipovic MR, Grill P, Michalke B, Ivanović-Burmazović I (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Inorganic Biochemistry Elsevier

Book Volume: 252

Article Number: 112478

DOI: 10.1016/j.jinorgbio.2024.112478

Abstract

The zinc complexes of chloroquine (CQ; [Zn(CQH+)Cl3]) and hydroxychloroquine (HO-CQ; [Zn(HO-CQH+)Cl3]) were synthesized and characterized by X-Ray structure analysis, FT-IR, NMR, UV–Vis spectroscopy, and cryo-spray mass spectrometry in solid state as well as in aqueous and organic solvent solutions, respectively. In acetonitrile, up to two Zn2+ ions bind to CQ and HO-CQ through the tertiary amine and aromatic nitrogen atoms (KN-aminCQ = (3.8 ± 0.5) x 104 M−1 and KN-aromCQ = (9.0 ± 0.7) x 103 M−1 for CQ, and KN-aminHO-CQ = (3.3 ± 0.4) x 104 M−1 and KN-aromHO-CQ = (1.6 ± 0.2) x 103 M−1 for HO-CQ). In MOPS buffer (pH 7.4) the coordination proceeds through the partially deprotonated aromatic nitrogen, with the corresponding equilibrium constants of KN-arom(aq)CQ = (3.9 ± 1.9) x 103 M−1and KN-arom(aq)HO-CQ = (0.7 + 0.4) x 103 M−1 for CQ and HO-CQ, respectively. An apparent partition coefficient of 0.22 was found for [Zn(CQH+)Cl3]. Mouse embryonic fibroblast (MEF) cells were treated with pre-synthesized [Zn((HO-)CQH+)Cl3] complexes and corresponding ZnCl2/(HO-)CQ mixtures and zinc uptake was determined by application of the fluorescence probe and ICP-OES measurements. Administration of pre-synthesized complexes led to higher total zinc levels than those obtained upon administration of the related zinc/(hydroxy)chloroquine mixtures. The differences in the zinc uptake between these two types of formulations were discussed in terms of different speciation and character of the complexes. The obtained results suggest that intact zinc complexes may exhibit biological effects distinct from that of the related zinc/ligand mixtures.

Authors with CRIS profile

Constantin Onderka Department Chemie und Pharmazie Jens Langer Lehrstuhl für Anorganische und Metallorganische Chemie

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Leibniz-Institut für Analytische Wissenschaften / Leibniz Institute for Analytical Sciences (ISAS) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Squarcina, A., Franke, A., Senft, L., Onderka, C., Langer, J., Vignane, T.,... Ivanović-Burmazović, I. (2024). Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake. Journal of Inorganic Biochemistry, 252. https://doi.org/10.1016/j.jinorgbio.2024.112478

MLA:

Squarcina, Andrea, et al. "Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake." Journal of Inorganic Biochemistry 252 (2024).

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