Elsevier

Polyhedron

Volume 161, 15 March 2019, Pages 179-188
Polyhedron

Synthesis, characterization, theoretical and cytotoxicity studies of Pd(II) and Pt(II) complexes with new bidentate carbon donor ligand

https://doi.org/10.1016/j.poly.2019.01.016Get rights and content

Abstract

The new phosphonium salt, the C,C-chelating phosphorus ylide ligand, (MeOC6H5C(O)CHdouble bondPPh2(CH2)2PPh2double bondCHC(O)C6H5OMe), and its Pd(II) and Pt(II) complexes have been synthesized and the cytotoxic activity of the synthesized complexes against three human cancer cell lines, including HeLa (Human cervix cancer cell line), KB (human oral cancer cell line) and U87 MG (human glioblastoma cell line) were evaluated using an MTT assay. The new compounds were identified and characterized using multinuclear (1H, 13C and 31P) NMR, infrared (IR) spectroscopy, elemental analysis, and through UV absorption and fluorescence emission spectra. Also, the crystal structure of the phosphorus ylide ligand was determined by single-crystal X-ray diffraction analysis. According to the obtained results from the MTT assay, the Pd(II) and Pt(II) complexes demonstrated a higher cytotoxic activity against KB human oral cancer cells in comparison with other cell lines, rendering these compounds into suitable candidates for further anti-oral cancer studies. Furthermore, a theoretical study on structure and nature of the Msingle bondC bonding between the Y ligand (ylide) and MCl2 fragment in the [YMCl2] (M = Pd, Pt and Y = (MeOC6H5C(O)CHdouble bondPPh2(CH2)2PPh2double bondCHC(O)C6H5OMe)) complexes have been reported via NBO and energy-decomposition analysis (EDA).

Graphical abstract

Two mononuclear Pd/Pt complexes with new bidentate carbon donor ligand have been synthesized. All newly synthesized compounds were characterized by X-ray analysis and physicochemical and spectroscopic data. Theoretical study on the structure of all complexes was investigated. Cytotoxic activity of all complexes has been performed.

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Introduction

In recent years, the coordination and organometallic chemistry of α-ketostabilized phosphorus ylides have undergone substantial development and have found widespread applications in synthetic organic chemistry, especially in the synthesis of naturally occurring products with biological and pharmacological activities [1], [2], [3], [4]. C,C-chelating phosphorus ylides, derived from bisphosphines, viz., RC(O)CHdouble bondPPh2(CH2)2PPh2double bondCHC(O)R (R = alkyl or aryl groups) [5], [6] show interesting properties such as a high stability, which allows them to be easily handled in air, and an ambidentate ligand character, due to the C-coordination (Fig. 1).

Although the preparation and characterization of transition metal complexes, containing α-ketostabilized phosphorus ylides, have been known since the last century [7], [8], [9], interest in these compounds has increased significantly in recent years. This interest has been driven primarily by the necessity to develop new reagents for chemical synthesis that exhibit enhanced properties [10], [11]. However, the synthesis of C,C-chelating phosphorus ylides, and the study of their complexation to transition metals, is a less documented field and only very few examples have been reported in the literature [12], [13], [14], in spite of their practical importance [15], [16]. Synthesis of transition metal complexes, derived from C,C-chelating phosphorus ylides has started in 2000 by Spannenberg et al. [5]. In 2014, we reported the synthesis of Pd(II) complexes containing such C,C-chelating phosphorus ylides [6].

As part of our interest in transition metal chemistry of C,C-chelating phosphorus ylides, we now focus on the synthesis, electronic and geometric properties of new transition metal complexes with the aim of studying their biological activities. The modern use of transition metal complexes as chemotherapeutic agents dates back returns to the discovery of cisplatin by Rosenberg and co-workers, followed by one of the most impressive drug success stories ever and a significant improvement of cancer therapy [17], [18], [19], [20], [21], [22]. In general, cisplatin and other platinum-based compounds such as carboplatin and oxaliplatin are considered as cytotoxic drugs ultimately leading to programmed cell death by damaging DNA, inhibiting tumor cell division, and inducing apoptosis. Nevertheless, because of serious side effects associated with cisplatin prevent the effectiveness of this compound and significant attempts have been made to replace cisplatin and its derivatives, by more efficient cytotoxic complexes with other transition metals and new ligands. Pd(II) and Pt(II) complexes containing phosphorus ylides are square-planar d8, isoelectronic and isostructural, and therefore appear to be very good candidates for anticancer investigations [23]. In some systems, Pd(II) complexes have greater activity than Pt(II) analogues [24], [25], [26], [27], [28]. However, studies on the cytotoxic properties of Pd(II) and Pt(II) complexes containing C,C-chelating phosphorus ylides, have not yet been reported. Herein we report the synthesis and characterization of a new C,C-chelating phosphorus ylide ligand and its Pd(II) and Pt(II) complexes. Also, the cytotoxic potential of these C,C-chelating phosphorus ylide Pd(II)/Pt(II) complexes were evaluated against three human cancer cell lines including HeLa, KB and U87 MG by an MTT assay.

Section snippets

General

In this study, starting materials and solvents were purchased from Aldrich or Merck and used without further purification. All the reactions were carried out under an atmosphere of dry nitrogen. Infrared spectra were recorded on a Shimadzu 435-U-04 spectrophotometer in the spectral range of 4000–400 cm−1 using the KBr pellets technique. Melting points were measured on a SMPI apparatus and are reported without correction. UV–vis spectra were recorded on a Perkin voyager DE-PRO spectrometer in

Synthesis and spectroscopic characterization

In the present research, the reaction of the diphosphine Ph2P(CH2)2PPh2 with 2 equiv of the 3-methoxyacetophenone for 24 h in acetone gave the corresponding phosphonium salt 1 in good yield. Further treatment with [(CH3)3Si]2NNa led to two-fold elimination of 2 mol HBr, giving the phosphorus ylide 2. The reactions of [MCl2(COD)] (M = Pd and Pt) with phosphorus ylide 2 in a 1:1 molar ratio yielded the C,C-chelated complexes 3 and 4 (Scheme 1).

IR spectral data of the synthesized phosphonium salt

Conclusion

Herein, the synthesis and characterization of a new C,C-chelating phosphorus ylide ligand and its palladium(II) and platinum(II) complexes are reported. The structures of the phosphonium salt and the phosphorus ylide ligand were confirmed by single crystal X-ray diffraction analysis. On the basis of the physicochemical and spectroscopic data, we propose that the ligand herein exhibits a chelating Csingle bondC coordination behavior to the metal center, affording a seven-membered chelate ring. Likewise, in

Acknowledgements

Funding of our research from the Bu-Ali Sina University is gratefully acknowledged.

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