The Fluorine Effect in Zwitterionic Half-Sandwich Iridium(III) Anticancer Complexes.

Author(s) Yang, Y.; Guo, L.; Ge, X.; Zhu, T.; Chen, W.; Zhou, H.; Zhao, L.; Liu, Z.
Journal Inorg Chem
Date Published 2020 Jan 06

The rational design by the introduction of fluorine into a compound has achieved success in the development of organic anticancer drugs. However, the fluorine effect in metal-based anticancer complexes has rarely been reported. In this contribution, we report the synthesis, characterization, chemical reactivity, and biological activity of a series of half-sandwich zwitterionic iridium(III) complexes containing different substituents in the η-Cp ring. The molecular structures for complexes - and were determined by single-crystal X-ray crystallography techniques. Notably, the asymmetrically substituted fluoro complexes and in solution show two conformational isomers. These complexes have sufficient stability, exhibit fluorescence emission, and show potent catalytic activity in converting NADH to NAD. The effect of the substituents in the η-Cp ring for these zwitterionic complexes on their anticancer activity was systematically investigated. Surprisingly, the presence of fluorinated substituents gives rise to a significant increase in the anticancer activity. The lipophilicity and cellular uptake levels of these complexes appeared to be the primary factors for their cytotoxicity in this system. A microscopic mechanism study showed that the typical complex entered A549 cancer cells through an energy-dependent pathway and was mainly located in lysosomes. Furthermore, an increase in ROS level, apoptosis induction, and cell-cycle perturbation together contribute to the anticancer potency of these zwitterionic complexes.

DOI 10.1021/acs.inorgchem.9b03006
ISSN 1520-510X
Citation Yang Y, Guo L, Ge X, Zhu T, Chen W, Zhou H, et al. The Fluorine Effect in Zwitterionic Half-Sandwich Iridium(III) Anticancer Complexes. Inorg Chem. 2020;59(1):748-758.

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