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α-Diimines as Versatile, Derivatizable Ligands in Ruthenium(II) p-Cymene Anticancer Complexes.
Journal article

α-Diimines as Versatile, Derivatizable Ligands in Ruthenium(II) p-Cymene Anticancer Complexes.

  • Biancalana L Dipartimento di Chimica e Chimica Industriale , Università di Pisa , Via G. Moruzzi 13 , I-56124 Pisa , Italy.
  • Batchelor LK Institut des Sciences et Ingénierie Chimiques , Ecole Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland.
  • Funaioli T Dipartimento di Chimica e Chimica Industriale , Università di Pisa , Via G. Moruzzi 13 , I-56124 Pisa , Italy.
  • Zacchini S Dipartimento di Chimica Industriale "Toso Montanari" , Università di Bologna , Viale Risorgimento 4 , I-40136 Bologna , Italy.
  • Bortoluzzi M Dipartimento di Scienze Molecolari e Nanosistemi , Università Ca' Foscari Venezia , Via Torino 155 , I-30170 Mestre, Venice , Italy.
  • Pampaloni G Dipartimento di Chimica e Chimica Industriale , Università di Pisa , Via G. Moruzzi 13 , I-56124 Pisa , Italy.
  • Dyson PJ Institut des Sciences et Ingénierie Chimiques , Ecole Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland.
  • Marchetti F Dipartimento di Chimica e Chimica Industriale , Università di Pisa , Via G. Moruzzi 13 , I-56124 Pisa , Italy.
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  • 2018-05-24
Published in:
  • Inorganic chemistry. - 2018
Antineoplastic Agents
Aspirin
Cell Line, Tumor
Cisplatin
Coordination Complexes
Cymenes
Drug Stability
Electrochemical Techniques
Humans
Imines
Ligands
Models, Chemical
Monoterpenes
Quantum Theory
Ruthenium
Solubility
Valproic Acid
Water
English α-Diimines are among the most robust and versatile ligands available in synthetic coordination chemistry, possessing finely tunable steric and electronic properties. A series of novel cationic ruthenium(II) p-cymene complexes bearing simple α-diimine ligands, [(η6- p-cymene)RuCl{κ2 N-(HCNR)2}]NO3 (R = Cy, [1]NO3; R = 4-C6H10OH, [2]NO3; R = 4-C6H4OH, [3]NO3), were prepared in near-quantitative yields as their nitrate salts. [2]NO3 displays high water solubility. The potential of the α-diimine ligand in [3]NO3 as a carrier of bioactive molecules was investigated via esterification reactions with the hydroxyl groups. Thus, the double-functionalized derivatives [(η6- p-cymene)RuCl{κ2 N-(HCN(4-C6H4OCO-R))2}]NO3 (R = aspirinate, [5]NO3; valproate, [6]NO3) and also [4]Cl (R = Me) were obtained in good-to-high yields. UV-vis and multinuclear NMR spectroscopy and cyclic voltammetric studies in aqueous solution revealed only minor ruthenium chloride hydrolytic cleavage, biologically accessible reduction potentials, and pH-dependent behavior of [3]NO3. Density functional theory analysis was performed in order to compare the Ru-Cl bond strength in [1]+ with the analogous ethylenediamine complex, showing that the higher stability observed in the former is related to the electron-withdrawing properties of the α-diimine ligand. In vitro cytotoxicity studies were performed against tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines, with the complexes bearing simple α-diimine ligands ranging from inactive to IC50 values in the low micromolar range. The complexes functionalized with bioactive components, i.e., [5]NO3 and [6]NO3, exhibited a marked increase in the cytotoxicity with respect to the precursor [3]NO3.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://susi.usi.ch/global/documents/86476
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