Novel Cerium(IV) Coordination Compounds of Monensin and Salinomycin

Abstract

The largely uncharted complexation chemistry of the veterinary polyether ionophores, monensic and salinomycinic acids (HL) with metal ions of type M4+ and the known antiproliferative potential of antibiotics has provoked our interest in exploring the coordination processes between MonH/SalH and ions of Ce4+. (1) Methods: Novel monensinate and salinomycinate cerium(IV)-based complexes were synthesized and structurally characterized by elemental analysis, a plethora of physicochemical methods, density functional theory, molecular dynamics, and biological assays. (2) Results: The formation of coordination species of a general composition [CeL2(OH)2] and [CeL(NO3)2(OH)], depending on reaction conditions, was proven both experimentally and theoretically. The metal(IV) complexes [CeL(NO3)2(OH)] possess promising cytotoxic activity against the human tumor uterine cervix (HeLa) cell line, being highly selective (non-tumor embryo Lep-3 vs. HeLa) compared to cisplatin, oxaliplatin, and epirubicin.

Experimental and DFT Study of Monensinate and Salinomycinate Complexes Containing {Fe3(µ3–O)}7+ Core

“…Such “head-to-tail” cyclization accompanied by a cave-hosted water molecule or hydroxide ion is a common feature of polyether ionophores [ 33 , 42 , 43 ], but the unambiguous coordination mode and the folding of the antibiotics can only be proved by X-ray diffraction on monocrystals. Unfortunately, our attempts to grow suitable crystals were unsuccessful; that is why we used several spectral techniques to explore the structure of the target complexes.…”

“…A member of this group—salinomycin, shows a substantial effect on cancer cells and cancer stem cells [ 18 , 31 , 32 ]. Another representative is monensin, which possesses less pronounced anticancer activity compared to salinomycin but has potential to be included in cancer therapy, due to the high selectivity index of some of its recently studied metal complexes [ 33 ]. Both antibiotics are polyether derivatives of monocarboxylic acids and, similarly to carboxylate siderophores, they may serve as potential ligands for iron(III) binding.…”

Synthesis, Spectral Characterization, and Structural Modelling of Di- and Trinuclear Iron(III) Monensinates with Different Bridging Patterns

“…The following approaches and devices were utilized in the present study: infrared spectroscopy (IR) on a Nicolet 6700 FT-IR spectrometer (Thermo Scientific, Madison, WI, USA); thermogravimetry (TG-DTA, TG-MS) on a Setaram Labsys Evo 1600 (Caluire-et-Cuire, France); electron paramagnetic resonance (EPR) on a Bruker BioSpin EMXplus10/12 EPR spectrometer (Karlsruhe, Germany); nuclear magnetic resonance (NMR) on a Bruker NEO 600 spectrometer (Karlsruhe, Germany); 57 Fe Mössbauer measurements on a Wissel spectrometer (Wissenschaftliche Elektronik GmbH, Starnberg, Germany); microanalysis on a Vario MACRO cube Elementar analysensysteme Gmbh (Stuttgart, Germany) (C, H) and Perkin-Elmer SCIEX-ELAN DRC-e ICP-MS (Massachusetts, USA) (Fe). Details of the technical parameters of the spectrometers and the corresponding sample preparation procedures are described in [41,59].…”