Locked and Loaded: Ruthenium(II)-Capped Cucurbit[ n]uril-Based Rotaxanes with Antimetastatic Properties

Martin Sojka; Michaela Fojtu; Jindriska Fialova; Michal Masarik; Marek Necas; Radek Marek

doi:10.1021/acs.inorgchem.9b01203

Locked and Loaded: Ruthenium(II)-Capped Cucurbit[ n]uril-Based Rotaxanes with Antimetastatic Properties

Inorg Chem. 2019 Aug 19;58(16):10861-10870. doi: 10.1021/acs.inorgchem.9b01203. Epub 2019 Jul 29.

Authors

Martin Sojka^{1

2}, Michaela Fojtu^{2

3

4}, Jindriska Fialova⁴, Michal Masarik^{2

3

4}, Marek Necas^{1

2}, Radek Marek^{1

2}

Affiliations

¹ Department of Chemistry, Faculty of Science , Masaryk University , Kamenice 5 , CZ-62500 Brno , Czechia.
² CEITEC-Central European Institute of Technology , Masaryk University , Kamenice 5 , CZ-62500 Brno , Czechia.
³ Department of Pathological Physiology, Faculty of Medicine , Masaryk University , Kamenice 5 , CZ-62500 Brno , Czechia.
⁴ Department of Physiology, Faculty of Medicine , Masaryk University , Kamenice 5 , CZ-62500 Brno , Czechia.

PMID: 31355636
DOI: 10.1021/acs.inorgchem.9b01203

Abstract

We report here the first coupling of Ru(II) units with cucurbit[6/7]uril-based pseudorotaxane ligands meant for biological application. The resulting ruthenium-capped rotaxanes were fully characterized, and a structure of one supramolecular system was determined by X-ray diffraction. Because the biological properties of Ru-based metallodrugs are tightly linked to the ligand-exchange processes, the effect of salt concentration on the hydrolysis of chlorides from the Ru(II) center was monitored by using ¹H NMR spectroscopy. The biological activity of Ru(II)-based rotaxanes was evaluated for three selected mammalian breast cell lines, HBL-100, MCF-7, and MDA-MB-231. The antimetastatic activity of the assembled cationic Ru(II)-rotaxane systems, evaluated in migration assays against MCF-7 and MDA-MB-231 cell lines, is notably enhanced compared to that of RAPTA-C, a reference that was used. The indicated synergistic effect of combining Ru(II) with a pseudorotaxane unit opens a new direction in searching for anticancer supramolecular metallodrugs.