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

被引:53
|
作者
Biancalana, Lorenzo [1 ]
Batchelor, Lucinda K. [2 ]
Funaioli, Tiziana [1 ]
Zacchini, Stefano [3 ]
Bortoluzzi, Marco [4 ]
Pampaloni, Guido [1 ]
Dyson, Paul J. [2 ]
Marchetti, Fabio [1 ]
机构
[1] Univ Pisa, Dipartimento Chim & Chim Ind, Via G Moruzzi 13, I-56124 Pisa, Italy
[2] Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland
[3] Univ Bologna, Dipartimento Chim Ind Toso Montanari, Viale Risorgimento 4, I-40136 Bologna, Italy
[4] Univ Ca Foscari Venezia, Dipartirnento Sci Mol & Nanosistemi, Via Torino 155, I-30170 Venice, Italy
基金
瑞士国家科学基金会;
关键词
INHIBITOR VALPROIC ACID; ARENE COMPLEXES; HUMAN OVARIAN; IN-VITRO; CONDUCTIVITY MEASUREMENTS; GLYOXAL DERIVATIVES; COORDINATION MODES; ANTITUMOR-ACTIVITY; PHASE I; METAL;
D O I
10.1021/acs.inorgchem.8b00882
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
alpha-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 a-diimine ligands, [(eta(6)-p-cymene)RuCl{kappa N-2-(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 a-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 [(eta(6)-p-cymene)RuCl{kappa N-2-(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 adiimine ligand. In vitro cytotoxicity studies were performed against tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines, with the complexes bearing simple a-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.
引用
收藏
页码:6669 / 6685
页数:17
相关论文
共 50 条
  • [1] P-CYMENE RUTHENIUM(II) COMPLEXES WITH 3-SUBSTITUTED PYRAZOLE LIGANDS
    CARMONA, D
    FERRER, J
    MARZAL, IM
    ORO, LA
    TROFIMENKO, S
    GAZZETTA CHIMICA ITALIANA, 1994, 124 (01): : 35 - 42
  • [2] Imine-N-Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p-Cymene Anticancer Complexes: A Structure-Activity Relationship Study
    Yang, Yuliang
    Guo, Lihua
    Tian, Zhenzhen
    Liu, Xicheng
    Gong, Yuteng
    Zheng, Hongmei
    Ge, Xingxing
    Liu, Zhe
    CHEMISTRY-AN ASIAN JOURNAL, 2018, 13 (19) : 2923 - 2933
  • [3] Versatile coordination of acetazolamide to ruthenium(II) p-cymene complexes and preliminary cytotoxicity studies
    Biancalana, Lorenzo
    Batchelor, Lucinda K.
    Ciancaleoni, Gianluca
    Zacchini, Stefano
    Pampaloni, Guido
    Dyson, Paul J.
    Marchetti, Fabio
    DALTON TRANSACTIONS, 2018, 47 (28) : 9367 - 9384
  • [4] p-Cymene Complexes of Ruthenium(II) as Antitumor Agents
    Angeles Pujante-Galian, Maria
    Perez, Sergio A.
    Montalban, Mercedes G.
    Carissimi, Guzman
    Fuster, Marta G.
    Villora, Gloria
    Garcia, Gabriel
    MOLECULES, 2020, 25 (21):
  • [5] Anticancer Organometallic Osmium(II)-p-cymene Complexes
    Paunescu, Emilia
    Nowak-Sliwinska, Patrycja
    Clavel, Catherine M.
    Scopelliti, Rosario
    Griffioen, Arjan W.
    Dyson, Paul J.
    CHEMMEDCHEM, 2015, 10 (09) : 1539 - 1547
  • [6] p-cymene ruthenium thioether complexes
    Cubrilo, Jadranka
    Hartenbach, Ingo
    Lissner, Falk
    Schleid, Thomas
    Niemeyer, Mark
    Winter, Rainer F.
    JOURNAL OF ORGANOMETALLIC CHEMISTRY, 2007, 692 (07) : 1496 - 1504
  • [7] Antiangiogenic and Anticancer Properties of Bifunctional Ruthenium(II)-p-Cymene Complexes: Influence of Pendant Perfluorous Chains
    Nowak-Sliwinska, Patrycja
    Clavel, Catherine M.
    Paunescu, Emilia
    te Winkel, Marije T.
    Griffioen, Arjan W.
    Dyson, Paul J.
    MOLECULAR PHARMACEUTICS, 2015, 12 (08) : 3089 - 3096
  • [8] The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity
    Vajs, Jure
    Steiner, Ivana
    Brozovic, Anamaria
    Pevec, Andrej
    Ambriovic-Ristov, Andreja
    Matkovic, Marija
    Piantanida, Ivo
    Urankar, Damijana
    Osmak, Maja
    Kosmrlj, Janez
    JOURNAL OF INORGANIC BIOCHEMISTRY, 2015, 153 : 42 - 48
  • [9] Ru(II)-p-Cymene Complexes of Furoylthiourea Ligands for Anticancer Applications against Breast Cancer Cells
    Dorairaj, Dorothy Priyanka
    Haribabu, Jebiti
    Dharmasivam, Mahendiran
    Malekshah, Rahime Eshaghi
    Subarkhan, Mohamed Kasim Mohamed
    Echeverria, Cesar
    Karvembu, Ramasamy
    INORGANIC CHEMISTRY, 2023, 62 (30) : 11761 - 11774
  • [10] Luminescent anticancer ruthenium(ii)-p-cymene complexes of extended imidazophenanthroline ligands: synthesis, structure, reactivity, biomolecular interactions and live cell imaging
    Sarkar, Bidisha
    Mondal, Ashaparna
    Madaan, Yukti
    Roy, Nilmadhab
    Moorthy, Anbalagan
    Kuo, Yung-Chih
    Paira, Priyankar
    DALTON TRANSACTIONS, 2019, 48 (32) : 12257 - 12271