Elsevier

Inorganica Chimica Acta

Volume 430, 1 May 2015, Pages 36-45
Inorganica Chimica Acta

Acetylacetonato chelated ruthenium organometallics incorporating imine–phenol function: Spectroscopic, structural, electrochemical and cytotoxicity studies

https://doi.org/10.1016/j.ica.2015.02.023Get rights and content

Highlights

  • Acetylacetonato chelated ruthenium(II) organometallic complexes.

  • Schiff base ligand has undergone a large rotation due to steric repulsion.

  • Geometry optimizations of the complexes were performed in the gas phase.

  • Electronic structure and the absorption spectra of the complexes are scrutinized.

  • The complexes have growth-inhibitory effect on MCF-7 cells, inducing sub G0 cell-cycle arrest.

Abstract

The heterogeneous phase reaction of Ru(η2-RL)(PPh3)2(CO)Cl, 1 with lithium acetylacetonate (Liacac) afforded the complexes of the type Ru(η1-RL)(PPh3)2(CO)(acac), 2 in excellent yield where η2-RL is C6H2O-2-CHNHC6H4R(p)-3-Me-5 and η1-RL is C6H2OH-2-CHNC6H4R(p)-3-Me-5 and R is H, Me, Cl. The chelation of acac is attended with the cleavage of Ru–O and Ru–Cl bonds and iminium–phenolato  imine–phenol prototropic shift. A sterically controlled change in rotational conformation is involved in the 1  2 conversion. The conversion is irreversible and the type 2 species are thermodynamically more stable than the carboxylate, nitrite and nitrate complexes of 1. The crystal structures of Ru(η1-MeL)(PPh3)2(CO)(acac), 2(Me) and Ru(η1-ClL)(PPh3)2(CO)(acac), 2(Cl) are reported. Spectral (UV–Vis, IR, 1H NMR) and electrochemical data of the complexes are also reported. The electronic structure and the absorption spectra of the complexes are scrutinized by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) analyses. The complexes were also screened in vitro for their antiproliferative properties against the MCF-7 breast cancer cell lines by using the MTT assay. Flow cytometric analysis showed that the complexes arrested the cell cycle in the sub G0 phase.

Graphical abstract

A series of acetylacetonato chelated ruthenium(II) organometallic complexes have been prepared and characterized by different spectroscopic techniques and by X-ray crystallography. Acetylacetonato chelation is attended with the cleavage of the Ru–O and Ru–Cl bonds and by the iminium–phenolato to imine–phenol prototropic shift. Density functional theory and time-dependent density functional theory calculations are also reported.

  1. Download : Download high-res image (50KB)
  2. Download : Download full-size image

Introduction

The reaction of the Schiff mono bases of 4-methyl-2,6-diformylphenol with Ru(PPh3)3Cl2 in ethanol afforded the novel ruthenium organometallics of type Ru(η2-RL)(PPh3)2(CO)Cl 1 by decarbonylative orthometallation [1]. The four membered metallacycle incorporating the phenolato function is unprecedented and the CO ligand lies cis to the orthometallated carbon where the aldehyde function was attached before decarbonylative metallation. Also notable is the iminium–phenolato zwitterionic function in the six-membered hydrogen bonded chelate ring.The reactivity of these compounds has also been investigated. Complex 1 undergoes facile regiospecific insertion of alkynes into the Ru–C(aryl) bond [2], [3] of the four membered metallacycle ring making it six-membered. Isonitriles have also been found to insert into the Ru–O bond of 1 promoting metallacycle expansion [4]. It has also been observed that mono-anionic σ-donor ligands such as carboxylate [5], nitrate, nitrite [6], xanthate [7] and pyridine-2-thiolate [8] undergo four-membered chelation via displacement of Ru–O and Ru–Cl bonds affording new organometallics. A facile reaction has also been observed between 1 and 2,2′-bipyridine or 1,10-phenanthroline [9] leading to five-membered α-diimine chelation. All the ligands cited above either make four or five-membered chelation with 1, but none has yet been reported in which six-membered chelation with 1 is present.

In the present work we are exploring the feasibility of introducing a six-membered chelate ring into the organometallic frame of 1 via displacement of Ru–O and Ru–Cl bonds using β-diketonate as the incoming ligand. This ligand choice was based on the reported affinity of β-diketonate for ruthenium [10], [11], [12], [13], [14]. A facile reaction has indeed been observed between 1 and lithium acetylacetonate in dichloromethane–acetone–water medium leading to six-membered O,O-chelated organometallics of type Ru(η1-RL)(PPh3)2(CO)(η2-acac) 2, the structure and properties of which are described in this work.

Investigations into the development of new anticancer drugs have highlighted ruthenium as a potential metal center [15], [16], [17] because ruthenium possesses several favorable properties such as cytotoxicity against cancer cells, similar exchange properties to those of Pt(II) complexes and is easily absorbed and rapidly excreted by the body. It also has reduced toxicity against healthy tissues due to transferrin transport [18], [19]. Several ruthenium complexes have displayed promising anticancer activity [20], [21]. Cytotoxicity of the complexes of type 1 or its derivatives has not been reported earlier. This has prompted us to examine the cytotoxicity of the complexes of type 2 with the human breast cancer cell line MCF-7 which was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay. The cell cycle arrest was also analyzed by flow cytometry. We have also examined the effect of different para-substituent of the Schiff base ligand (η1-RL) on the antiproliferative effect of the complexes of type 2.

To get better insight into the electronic structure and optical properties of these complexes, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) studies have also been presented. These combined experimental and theoretical studies provide the first detailed investigation of the electronic structure of the complexes of type 2.

Section snippets

Materials and methods

The compound Ru(η2-RL)(PPh3)2(CO)Cl 1 was prepared by the literature method [1]. Lithium acetylacetonate (Liacac) was purchased from Sigma Aldrich, India. All other reagents were obtained from commercial sources and were used as received. Infrared spectra were recorded on a Perkin-Elmer L120-00A FT-IR spectrometer as a KBr pellet. Electronic spectra were recorded on a Shimadzu UV-1800 PC Spectrophotometer. 1H NMR spectra were collected on a Bruker DPX-400 spectrometer in CDCl3. Microanalyses

Synthesis and characterization

In dichloromethane–acetone solution Ru(η2-RL)(PPh3)2(CO)Cl 1 reacts smoothly with fivefold excess of aqueous lithium acetylacetonate (Liacac) furnishing a yellow solution from which Ru(η1-RL)(PPh3)2(CO)(η2-acac) 2 was isolated as yellow crystalline solid in excellent yield. The η1-RL ligand in 2 is a tautomeric form of η2-RL ligand [1] in 1. Three different R groups have been used in this work: H, Me and Cl. Specific compounds will be identified by putting R in parenthesis e.g. 2(H) stands for

Conclusions

The main finding of this work will now be summarized. It is demonstrated that Ru(η2-RL)(PPh3)2(CO)Cl 1 undergoes facile substitution of chloride by acetylacetonate affording a new family of aryl ruthenium species, Ru(η1-RL)(PPh3)2(CO)(acac) 2. The complexes are characterized by different spectroscopic techniques, elemental analysis and X-ray structure determination. Structure determination has revealed that in going from 1  2 the RL ligand changes its hapticity from η2 to η1 as the

Acknowledgments

Financial support from the Department of Science and Technology, Government of India (No. SR/S1/IC-65/2010) is gratefully acknowledged. University of Kalyani for infrastructural facilities. The support of DST under FIST program to the Department of Chemistry and PURSE to the University of Kalyani is also acknowledged. We are also thankful to Dr. Rajat Saha of Jadavpur University for help with the crystallography. S.M. thanks UGC, India and M. K. G. thanks University of Kalyani for the

References (38)

  • B.K. Panda et al.

    Polyhedron

    (2002)
  • B.K. Panda et al.

    J. Organomet. Chem.

    (2003)
  • S. Chatterjee et al.

    Inorg. Chim. Acta

    (2011)
  • P.C. Bruijnincx et al.

    Curr. Opin. Chem. Biol.

    (2008)
  • L. Bratsos et al.

    Chimia

    (2007)
  • T.F. Chen et al.

    J. Agric. Food Chem.

    (2008)
  • P. Ghosh et al.

    Organometallics

    (1996)
  • K. Ghosh et al.

    Organometallics

    (2001)
  • S. Chattopadhyay et al.

    J. Chem. Soc., Dalton Trans.

    (2001)
  • B.K. Panda et al.

    Organometallics

    (2002)
  • P. Ghosh et al.

    Organometallics

    (1996)
  • P. Ghosh et al.

    Inorg. Chem.

    (1997)
  • S. Chattopadhyay et al.

    Israel J. Chem.

    (2001)
  • D. Das et al.

    Chem. Eur. J.

    (2011)
  • P. Mondal et al.

    Inorg. Chem.

    (2013)
  • S. Kar et al.

    Inorg. Chem.

    (2004)
  • P.N. Liu et al.

    Chem. Eur. J.

    (2007)
    M.A. Bennett et al.

    J. Am. Chem. Soc.

    (1998)
    M.A. Bennett et al.

    Organometallics

    (1998)
  • J.M. Rademaker-Lakhai et al.

    Clin. Cancer Res.

    (2004)
  • C.G. Hartinger et al.

    J. Inorg. Biochem.

    (2006)
  • Cited by (8)

    • A series of ruthenium(II) organometallic complexes incorporating pyridine-2-carboxylato ligand: Detailed spectroscopic and computional studies

      2021, Journal of the Indian Chemical Society
      Citation Excerpt :

      The two Ru─P distances in the complex are more or less similar. Those distances fall within the range of the corresponding distances in other structurally characterized ruthenium complexes [36–48]. The chelation of the picolinate ligand to the Ru center in the complex results in the distortion of the angles around the central metal atom in such a way that the four equatorial angles differ considerably from the mean value of 90°.

    • Cleavage of Ru-C(aryl) bond of a four-membered ortho-metalated ruthenium(II) organometallics by mercaptopyrimidine and pyridine-2,6-dicarboxylate ligands: Spectroscopic, structural and computational studies

      2016, Polyhedron
      Citation Excerpt :

      The Ru1N1 distance is 2.031(3) Å and the Ru1O1 distance is slightly shorter than the RuO3 distance [Ru1O1: 2.104(3) Å; Ru1O3: 2.125(3) Å]. The RuN and RuO distances in 3 CH3CN fall within the range of the corresponding distances in other structurally characterized pyridine-2,6-dicarboxylate complexes of ruthenium(II) [31]. The geometry optimization of the complexes 2 and 3 were performed in the gas phase assuming a singlet ground state (S = 0, t2g6) to get an insight into the ground state geometry, electronic structure and nature of FMOs of the complexes.

    • Honeycomb-shaped coordination polymers based on the self-assembly of long flexible ligands and alkaline-earth ions

      2016, Journal of Solid State Chemistry
      Citation Excerpt :

      Coordination polymers (CPs) consisting of inorganic metal ions or clusters and organic ligands, which may generate a huge number of novel interpenetration networks, have become one of the fastest growing fields in chemistry and attract immense interest. [1–5]. CPs may allow rational design strategies for assembling porous materials to target some diverse functionalities and potentially industrial applications, such as gas storage and separation, catalysis, guest-exchange, molecular recognition, magnetic properties and selective luminescent probes [6–19]. Obviously, the topological features the geometry of metal centers and the coordination mode of bridging ligands.

    View all citing articles on Scopus
    View full text