Cytotoxicity of osmium(II) and cycloosmated half-sandwich complexes from 1-pyrenyl-containing phosphane ligands

Dana Josa; David Aguilà; Pere Fontova; Vanessa Soto-Cerrato; Piedad Herrera-Ramírez; Laia Rafols; Arnald Grabulosa; Patrick Gamez

doi:10.1039/d3dt00743j

Cytotoxicity of osmium(II) and cycloosmated half-sandwich complexes from 1-pyrenyl-containing phosphane ligands

Dalton Trans. 2023 Jun 20;52(24):8391-8401. doi: 10.1039/d3dt00743j.

Authors

Dana Josa^{1

2}, David Aguilà^{1

2}, Pere Fontova³, Vanessa Soto-Cerrato^{4

5}, Piedad Herrera-Ramírez¹, Laia Rafols¹, Arnald Grabulosa^{1

2}, Patrick Gamez^{1

2

6}

Affiliations

¹ Departament de Química Inorgànica i Orgànica, Facultat de Química, Secció de Química Inorgànica, Universitat de Barcelona, Martí i Franquès, 1-11, 08028 Barcelona, Spain. arnald.grabulosa@qi.ub.es.
² Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, 08028 Barcelona, Spain.
³ Department of Chemistry, Universidad de Burgos, 09001 Burgos, Spain.
⁴ Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Campus Bellvitge, Feixa LLarga s/n, 08907 L'Hospitalet de Llobregat, Spain.
⁵ Oncobell Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain.
⁶ Catalan Institution for Research and Advanced Studies, Passeig Lluís Companys 23, 08010 Barcelona, Spain.

PMID: 37265269
DOI: 10.1039/d3dt00743j

Abstract

Five metal-arene complexes of formula [MX₂(η⁶-p-cymene)(diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl) and symbolized as MRX2 were synthesized and fully characterized, namely OsiPrCl2, OsiPrI2, OsPhCl2, OsPhI2 and RuPhI2. Furthermore, nine cyclometalated half-sandwich complexes of formula [MX-(η⁶-p-cymene)(k²C-diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl) or [M(η⁶-p-cymene)(kS-dmso)(k²C-diR(1-pyrenyl)phosphane)]PF₆ (M = Os or Ru, R = isopropyl or phenyl) and symbolized as c-MRX were prepared; hence, c-OsiPrCl, c-OsiPrI, c-OsiPrdmso, c-OsPhCl, c-OsPhI, c-OsPhdmso, c-RuPhCl, c-RuPhI and c-RuPhdmso were obtained and fully characterized. The crystal structures of ten out of the fourteen complexes were solved. All complexes exhibit notable cytotoxic properties against A549 (Lung Adenocarcinoma) human cells, with IC₅₀ values ranging from 48 to 1.42 μM. In addition, complex c-OsiPrdmso shows remarkable toxic behaviours agains other cell lines, namely MCF7 (breast carcinoma), MCF10A (non-tumorigenic epithelial breast) and MDA-MB-435 (melanoma) human cells, as illustrated by IC₅₀ values of 4.36, 4.71 and 2.32 μM, respectively. Finally, it has been found that OsiPrI2 affects the cell cycle of A549 cells, impeding their replication (i.e., the cell cycle is blocked), whereas OsPhI2 (namely with phenyl groups instead of isopropyl ones) does not induce this effect.