BODIPY–dipicolylamine complexes of platinum(ii): X-ray structure, cellular imaging and organelle-specific near-IR light type-II PDT. Issue 10 (16th February 2022)

• Record Type: Journal Article
• Authors: Bera, Arpan; Gautam, Srishti; Raza, Md Kausar; Pal, Apurba Kumar; Kondaiah, Paturu; Chakravarty, Akhil R.
• Is Part Of: Dalton transactions. Volume 51:Issue 10(2022)
• Page Start: 3925
• Page End: 3936
• Publication Date: 2022-02-16
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d1dt03200c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Pt(ii )-dipicolylamine-BODIPY based photosensitizers [Pt(L 2, 3 )Cl]Cl show remarkable mitochondria and ER-targeted type-II apoptotic PDT activity in visible and red light forming singlet oxygen as the ROS. Abstract : Dipicolylamine (dpa) based platinum(ii ) complexes [Pt(L 1–3 )Cl]Cl (1–3 ), where L 2 and L 3 are green and red light BODIPY-tagged dpa ligands and L 1 is a benzyl derivative of dpa, were synthesized and characterized and their in vitro cytotoxicity was studied. The perchlorate salt of complex 2 was structurally characterized. It showed a PtN3 Cl core with a deformed square-planar geometry. At pH 7.2, complexes 2 and 3 showed strong absorption bands at 500 nm ( ε ∼6.8 × 10 4 dm 3 mol −1 cm −1 ) and 653 nm ( ε ∼1.0 × 10 5 dm 3 mol −1 cm −1 ) in a 1 : 1 (v/v) mixture of dimethyl sulfoxide and Dulbecco's phosphate-buffered saline (DMSO/DPBS), respectively. They displayed respective emission bands at 515 and 677 nm having fluorescence quantum yield values of 0.36 and 0.25. Complex 3 generated singlet oxygen, as evidenced from the 1, 3-diphenylisobenzofuran titration experiments and mechanistic DNA photocleavage study. It showed high photocytotoxicity in red light (600–720 nm) with half-maximal inhibitory concentration (IC50 ) values of 1.73 and 2.67 μM in HeLa and A549 cells. The complexes showed significantly reduced chemo-PDT activity in a non-cancerous HPL1D cell line and in the dark. The 2′, 7′-dichlorofluorescein diacetate assay revealed reactive oxygen species-mediated type-II photodynamic therapy (PDT) activity. Cellular imaging of A549 cancer cells using complexes 2 and 3 revealed their preferential localization in mitochondria and endoplasmic reticulum. The annexin V-FITC/PI assay confirmed apoptotic cell damage. Cell cycle analysis indicated arrest in the G1 phase upon red light irradiation. Pt–DNA adduct formation was proposed from a DNA binding experiment with green light active complex 2 and 9-ethylguanine as a nucleobase from the mass spectral study.