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

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 M^R_X2 were synthesized and fully characterized, namely Os^iPr_Cl2, Os^iPr_I2, Os^Ph_Cl2, Os^Ph_I2 and Ru^Ph_I2. 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-M^R_X were prepared; hence, c-Os^iPr_Cl, c-Os^iPr_I, c-Os^iPr_dmso, c-Os^Ph_Cl, c-Os^Ph_I, c-Os^Ph_dmso, c-Ru^Ph_Cl, c-Ru^Ph_I and c-Ru^Ph_dmso 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-Os^iPr_dmso 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 Os^iPr_I2 affects the cell cycle of A549 cells, impeding their replication (i.e., the cell cycle is blocked), whereas Os^Ph_I2 (namely with phenyl groups instead of isopropyl ones) does not induce this effect.