Ru(II)-Arene Complexes of Curcumin and Bisdesmethoxycurcumin Metabolites.

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis.

Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions.

Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe, Ru] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η-CH)Fe(CO)(κ-PPh(CH)PPh)]{PF} (n = 1-5), compounds 1-5, and heterodinuclear [Fe, Ru] complexes, [(η-CH)Fe(CO)(μ-PPh(CH)PPh))(η-p-cymene)RuCl]{PF} (n = 2-5) (compounds 7-10), were synthesized and characterised.

Potent and selective anticancer activity of half-sandwich ruthenium and osmium complexes with modified curcuminoid ligands.

We have recently reported a series of half-sandwich ruthenium(II) complexes with curcuminoid ligands showing excellent cytotoxic activities (particularly ionic derivatives containing PTA (PTA = 1,3,5-triaza-7-phosphaadamantane). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of a long hydrophobic chain obtained by replacing the OH-groups, present in curcumin and bisdemethoxycurcumin, with the palmitic acid ester. We report the synthesis of ruthenium(II) and osmium(II) p-cymene derivatives containing palmitic acid curcumin ester ligands ((1,3,6)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl)bis(2-methoxy-4,1-phenylene)dipalmitate () and ((1,3,6)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl)bis(4,1-phenylene)dipalmitate ().

Role of the (pseudo)halido ligand in ruthenium(II) -cymene α-amino acid complexes in speciation, protein reactivity and cytotoxicity.

The reactions of the dimeric complexes [RuX(η--cymene)] (X = Br, I, SCN) with L-proline (ProH) and -4-hydroxy-L-proline (HypH), in methanol in the presence of NaOH, afforded [RuX(κ,-Pro)(η--cymene)] (X = Br, 1b; I, 1c; SCN, 1d) and [RuX(κ,-Hyp)(η--cymene)] (X = Br, 2b; I, 2c; SCN, 2d), respectively. Alternatively, the one-pot, sequential addition of the appropriate α-amino carboxylate and X salt to [RuCl(η--cymene)] led to [RuX(κ,-Pro)(η--cymene)] (X = N, 1e; NO, 1f; CN 1g) and [Ru(N)(κ,-Hyp)(η--cymene)] (2e). Complexes [Ru(κ,,'-OCCH(NH)(R)O)(η--cymene)] (R = CH, 3h; R = CHMe, 4h; R = CHCH, 5h) were prepared from the reaction of [RuCl(η--cymene)] with the appropriate α-amino acid and NaOH in refluxing isopropanol.

A Strategy to Conjugate Bioactive Fragments to Cytotoxic Diiron Bis(cyclopentadienyl) Complexes.

A series of bioactive molecules were synthesized from the condensation of aspirin or chlorambucil with terminal alkynes bearing alcohol or amine substituents. Insertion of the resulting alkynes into the iron-carbyne bond of readily accessible diiron bis(cyclopentadienyl) μ-aminocarbyne complexes, [,]CFSO, afforded novel diiron complexes with a bridging vinyliminium ligand, [-]CFSO, functionalized with a bioactive moiety. All compounds were characterized by elemental analysis and IR and multinuclear NMR spectroscopy and in three cases by single-crystal X-ray diffraction.

Hetero-Bis-Conjugation of Bioactive Molecules to Half-Sandwich Ruthenium(II) and Iridium(III) Complexes Provides Synergic Effects in Cancer Cell Cytotoxicity.

Four bipyridine-type ligands variably derivatized with two bioactive groups (taken from ethacrynic acid, flurbiprofen, biotin, and benzylpenicillin) were prepared via sequential esterification steps from commercial 2,2'-bipyridine-4,4'-dicarboxylic acid and subsequently coordinated to ruthenium(II) -cymene and iridium(III) pentamethylcyclopentadienyl scaffolds. The resulting complexes were isolated as nitrate salts in high yields and fully characterized by analytical and spectroscopic methods. NMR and MS studies in aqueous solution and in cell culture medium highlighted a substantial stability of ligand coordination and a slow release of the bioactive fragments in the latter case.