DFT studies of the full mechanistic Suzuki–Miyaura reaction: synthesis, structural analysis and cytotoxicity of P,C-chelated palladium(II) and platinum(II) complexes

Abstract

The new Pd/Pt(II) complexes, [MBr₂(Ph₂PCH₂PPh₂C(H)C(O)C₆H₄-m-Br)] (M = Pd (1); M = Pt (2)), with unsymmetrical phosphorus ylide [Ph₂PCH₂PPh₂=C(H)C(O)C₆H₄Br] (Y) have been synthesized through a simple procedure and were screened in a search for novel antitumor agents. These compounds were characterized by FT-IR, NMR (¹H, ¹³C and ³¹P) spectroscopic methods and density functional theory methods. The crystal structures of 1 and 2 were elucidated by single-crystal X-ray diffraction. The results indicated that the complexes were P,C-chelated. Also, a theoretical study on the structure of the complexes has been investigated at the BP86/def2-SVP level of theory. The nature of metal-ligand bonds in the complexes was analyzed using EDA and ETS-NOCV analyses. In particular, a mechanistic pathway of the Suzuki–Miyaura reaction catalyzed by Pd(II) complex 1 with a P,C-donor ligand has been investigated by DFT studies, which the computational results were in agreement with those of experiments. Moreover, the cytotoxic effects of the compounds were studied in four human carcinoma cell lines: PC3, A2780, MCF-7 and PC-12 by MTT assay. Compound 1 proved to be an outstanding potent cytotoxic agent against PC3 cell line and can be considered as a promising lead in cancer drug discovery and development.

Graphical Abstract

Keywords:

• Pd/Pt-cyclic complexes
• X-ray
• DFT
• catalyst
• cytotoxic

Supplementary material

Physical measurements and selected ³¹P, ¹³C and ¹H NMR spectra of some compounds can be found in the online version. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK. Tel.: [phone]; or [email protected].

Acknowledgements

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

Disclosure statement

No potential conflict of interest was reported by the author(s).