Half-Sandwich Ru(II) Halogenido, Valproato and 4-Phenylbutyrato Complexes Containing 2,2′-Dipyridylamine: Synthesis, Characterization, Solution Chemistry and In Vitro Cytotoxicity

Abstract

Halogenido and carboxylato Ru(II) half-sandwich complexes of the general composition [Ru(η 6 -p-cym)(dpa)X]PF 6 (1-5) were prepared and thoroughly characterized with various techniques (e.g., mass spectrometry, NMR spectroscopy and X-ray analysis); dpa = 2,2 -dipyridylamine; p-cym = p-cymene; X = Cl − (for 1), Br − (for 2), I − (for 3), valproate(1−) (for 4) or 4-phenylbutyrate(1−) (for 5). A single-crystal X-ray analysis showed a pseudo-octahedral piano-stool geometry of [Ru(η 6 -p-cym)(dpa)I]PF 6 (3), with a η 6 -coordinated p-cymene, bidentate N-donor dpa ligand and iodido ligand coordinated to the Ru(II) atom. The results of the 1 H-NMR solution behaviour studies proved that the complexes 1-5 hydrolyse were in the mixture of solvents used (10% MeOD-d 4 /90% D 2 O). Complexes 1-5 were in vitro inactive against the A2780 human ovarian carcinoma cell line, up to the highest tested concentration (IC 50 > 100 µM).

Half-Sandwich Ru(p-cymene) Compounds with Diphosphanes: In Vitro and In Vivo Evaluation As Potential Anticancer Metallodrugs

“…UV–vis spectra of the complexes were recorded at room temperature in ∼10 –4 –10 –6 M ethanol solutions under the same experimental conditions. The electronic spectra (see Figure S3 in the Supporting Information) showed a very intense band ascribed to π–π* electronic transitions occurring in the organometallic fragment Ru­( p -cymene) (λ 200–270 nm), a weak band assigned to metal–ligand charge-transfer transitions (MLCT) from Ru 4d orbitals to the π* orbitals of the ligands (λ 290–390 nm), and a shoulder assigned to d–d transitions (λ 400–600 nm), as has been reported in similar arene complexes …”

“…The electronic spectra (see Figure S3 in the Supporting Information) showed a very intense band ascribed to π−π* electronic transitions occurring in the organometallic fragment Ru(p-cymene) (λ 200−270 nm), a weak band assigned to metal−ligand charge-transfer transitions (MLCT) from Ru 4d orbitals to the π* orbitals of the ligands (λ 290−390 nm), and a shoulder assigned to d−d transitions (λ 400−600 nm), as has been reported in similar arene complexes. 60 The stability of complexes 1 and 2 in solution was evaluated over time by monitoring their UV profiles over a period of 24 h at room temperature (using 2−4% of DMSO to fully dissolve the complexes in aqueous media and cell culture media DMEM). Both complexes demonstrated a good stability in aqueous solution with minimal changes in their UV−visible spectra (see Figures S6−S8 in the Supporting Information).…”

Cell‐based studies of the first‐in‐class half‐sandwich Ir(III) complex containing histone deacetylase inhibitor 4‐phenylbutyrate

“…The 1 H NMR phen and Cp ph signals of complex 1‐PB showed in the same region as reported for complex 1‐Cl (supporting information, Figure S3). 5a The 1 H NMR signals of the aliphatic α‐CH 2 , β‐CH 2 and γ‐CH 2 hydrogens of free PB anion (measured on NaPB) shifted upfield by 0.89 ppm, 0.60 ppm and 0.24 ppm, respectively, after its coordination into the structure of complex 1‐PB , which is consistent with the [Ru(η 6 ‐ p cym)(dpa)(PB)]PF 6 complex . Only a small Δδ = 1.0 ppm was detected in the 13 C NMR spectra for the carboxyl carbon atom of the PB anion upon its coordination to the Ir(III) atom of complex 1‐PB .…”

“…Complex 1‐PB was prepared by the straightforward reaction of the previously reported chlorido complex 1‐Cl 5a with an excess of silver(I) 4‐phenylbutyrate (AgPB), as recently reported for Ru(II) complex [Ru(η 6 ‐ p cym)(dpa)(PB)]PF 6 ( p cym = p ‐cymene and dpa = 2,2`‐dipyridylamine) . Complex 1‐PB was isolated in a good yield and its 99.4% purity ( t R = 9.97 min) was determined by RP‐HPLC/ESI+ MS (supporting information, Figure S1).…”

“…Complexes [Ir(μ‐Cl)(η 5 ‐Cp ph )Cl] 2 and [Ir(η 5 ‐Cp ph )(phen)Cl]PF 6 ( 1‐Cl ) 5a were prepared using the modification of the reported procedures. The synthesis of silver(I) 4‐phenylbutyrate (AgPB) is described elsewhere …”