Unexpected solution behaviour of ester-functionalized half-sandwich Ru(ii) and Ir(iii) complexes. Issue 23 (19th May 2021)

• Record Type: Journal Article
• Authors: Masaryk, Lukáš; Nemec, Ivan; Kašpárková, Jana; Brabec, Viktor; Štarha, Pavel
• Is Part Of: Dalton transactions. Volume 50:Issue 23(2021)
• Page Start: 8017
• Page End: 8028
• Publication Date: 2021-05-19
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d1dt00466b
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Model multi-targeted half-sandwich Ru and Ir complexes, containing the ester-functionalized chelating ligands, were studied for their stability under various (pseudo)physiological conditions, including the presence of porcine liver esterase (PLE). Abstract : Complexes [Ru(η 6 -pcym)(bpy dca )Cl]PF6 (Ru dca ) and [Ir(η 5 -Cp*)(bpy dca )Cl]PF6 (Ir dca ) were developed as model compounds for the investigation of multi-targeted ester-functionalized half-sandwich ruthenium(ii ) and iridium(iii ) complexes; pcym = 1-methyl-4-(propan-2-yl)benzene ( p -cymene), bpy dca = 2, 2′-bipyridine-4, 4′-diyldimethanediyl bis(dichloroacetate), Cp* = pentamethylcyclopentadienyl. Aiming to understand the in-solution behaviour of these first-in-class complexes containing the pyruvate dehydrogenase kinase inhibitor dichloroacetate (dca) as the terminal bioactive substituent, several experiments were performed under aqueous conditions for Ru dca and Ir dca, as well as for compounds [Ru(η 6 -pcym)(bpy OH )Cl]PF6 (Ru OH ) and [Ir(η 5 -Cp*)(bpy OH )Cl]PF6 (Ir OH ), and acetyl analogues [Ru(η 6 -pcym)(bpy ac )Cl]PF6 (Ru ac ) and [Ir(η 5 -Cp*)(bpy ac )Cl]PF6 (Ir ac ) bearing a different (biologically inactive) terminal substituent; bpy OH = 2, 2′-bipyridine-4, 4′-diyldimethanol, bpy ac = 2, 2′-bipyridine-4, 4′-diyldimethanediyl diacetate. The experiments were also conducted in the presence of porcine liver esterase (PLE). All the six complexes were characterized by relevant techniques ( e.g., NMR and mass spectrometry), including a single-crystal X-ray analysis of complexes Ru dca, Ru ac, Ru OH and Ir OH . Although designed as model compounds, Ru dca, Ir dca, Ru OH and Ir OH were also screened for their antiproliferative activity in four human cancer cell lines (HCT116 colon carcinoma, MDA-MB-231 and MCF-7 breast adenocarcinomas, DU145 prostate carcinoma), where the tested complexes did not show any effect (IC50 > 100 μM).