Synthesis, characterization and biological application of cyclometalated heteroleptic platinum(II) complexes

• Published in: Applied organometallic chemistry 2018-02, Vol.32 (2), p.n/a
• Main Authors: Lunagariya, Miral V., Thakor, Khyati P., Patel, Nikita J., Patel, Mohan N.
• Format: Article
• Language: English
• Subjects: Acetylacetone; Bacteria; Binding; Chemistry; Coordination compounds; Cyclometalated heteroleptic Pt(II) complexes; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA interaction studies; Fluorescence; In vitro antibacterial assay; In vitro cytotoxicity assay; Lethality; Ligands; Molecular docking; N –donor bidentate ligands; Nuclease; Platinum; Pyrazolo[1,5‐a]pyrimidine based neutral C; Quenching; Saline water; Titration; Toxicity
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.4045

A series of square planar cyclometalated heteroleptic platinum(II) complexes of the type [(C^N)Pt(O^O)] [where, O^O is a β‐diketonato ligand of acetylacetone (acac), C^N = cyclometalating 7‐(4‐fluorophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L1), 7‐(4‐chlorophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L2), 7‐(4‐bromophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L3), 7‐(4‐methoxyphenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L4), 5‐phenyl‐7‐(p‐tolyl)pyrazolo[1,5‐a]pyrimidine (L5)] have been design, synthesized and characterized. All compounds have been screened for biological studies like in vitro antibacterial, in vitro cytotoxicity, cellular level cytotoxicity, absorption titration, viscosity measurements, fluorescence quenching analysis, molecular docking and DNA nuclease. The intrinsic binding constants (Kb) of compounds with HS‐DNA has been obtained in range of 2.892–0.242 × 105 M−1. All the compounds bound with HS DNA by partial intercalative mode of binding. MIC study has been carried out against Gram(+ve) and Gram(−ve) bacterial species. In vitro cytotoxicity against brine shrimp lethality bioassay has been also carried out. The LC50 values of the ligands and complexes have been found in range of 56.49–120.22 μg/mL and 6.71–11.96 μg/mL, respectively. Synthesis of organometallic Pt(II) complexes with heterocyclic pyrazolo[1,5‐a]pyrimidine derivatives bidentate C, N –donor ligands. Characterizationof the compounds was carried out by elemental analysis (C, H, N, S), 1H NMR, 13C NMR, FT‐IR, UV–visible, molar conductivity, mass spectroscopic and TGA spectroscopy. Accommodation of the organometallic Pt(II) complexes in the DNA base pairs as an partial intercalative mode of binding have been confirmed through molecular docking, absorption titration analysis, viscosity measurements and fluorescence quenching analysis. DNA cleavage assay was carried out by gel electrophoresis technique. All the heterocyclic compounds like, pyrazolo[1,5‐a]pyrimidine based ligands, cisplatin, transplatin and their cyclometalated Pt(II) complexes have been examined for in vitro antibacterial assay, in vitro cellular level cytotoxicity against S. Pombe cells, and in vitro cytotoxicity against brine shrimp lethality bioassay (LC50).