Anticancer Effect of an Electronically Coupled Oligoferrocene
Zeh G, Haines P, Miehlich M, Kienz T, Neidlinger A, Friedrich RP, Alexiou C, Hampel F, Guldi DM, Meyer K, Schatz J, Heinze K, Mokhir A (2020)
Publication Type: Journal article
Publication year: 2020
Journal
DOI: 10.1021/acs.organomet.0c00306
Abstract
The mode of anticancer activity of simple ferrocenes often relies on their intracellular oxidation with the formation of cytotoxic ferrocenium species. The former compounds should be considered as prodrugs and derived from them ferroceniums as drugs. The drugs are 17e- organometallic species. Therefore, they are chemically unstable and decompose with formation of free cyclopentadienyl ligands (which are further transformed to more stable species) and iron ions. The short lifetime of ferrocenium drugs limits the anticancer effect of ferrocene prodrugs. In this paper we prepared a series of acylated aminoferrocene monomers, dimers, and higher oligonuclear complexes FcN (where N = 1-4). Drugs [FcN]+ derived from FcN (N > 1) are more stable than monomeric [Fc]+, provided that the ferrocene units are electronically coupled. Correspondingly, we expected that FcN species will be more potent anticancer agents in comparison to the related monomers. These assumptions were confirmed for dimer 10. We observed that this prodrug has sufficient solubility in aqueous solution (100 μM) and favorable lipophilicity (log P = 2.2 ± 0.2). Ferrocene units in 10 are efficiently electronically coupled via a -C(═O)NH- linker according to cyclic voltammetry, differential pulse voltammetry, and spectroelectrochemistry. We observed that 10 is the most efficient catalyst of the production of reactive oxygen species (ROS) and the most active anticancer agent in comparison to control monomers and their mixtures.
Authors with CRIS profile
Gina Zeh
Lehrstuhl für Physikalische Chemie I
Philipp Haines
Lehrstuhl für Physikalische Chemie I
Matthias Miehlich
Lehrstuhl für Anorganische und Allgemeine Chemie
Christoph Alexiou
Professur für Nanomedizin
Frank Hampel
Lehrstuhl für Organische Chemie I
Dirk Michael Guldi
Lehrstuhl für Physikalische Chemie I
Karsten Meyer
Lehrstuhl für Anorganische und Allgemeine Chemie
Jürgen Schatz
Professur für Organische Chemie
Andriy Mokhir
Professur für Organische Chemie
Involved external institutions
Germany (DE)How to cite
APA:
Zeh, G., Haines, P., Miehlich, M., Kienz, T., Neidlinger, A., Friedrich, R.P.,... Mokhir, A. (2020). Anticancer Effect of an Electronically Coupled Oligoferrocene. Organometallics. https://doi.org/10.1021/acs.organomet.0c00306
MLA:
Zeh, Gina, et al. "Anticancer Effect of an Electronically Coupled Oligoferrocene." Organometallics (2020).
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