BODIPY‐Appended 2‐(2‐Pyridyl)benzimidazole Platinum(II) Catecholates for Mitochondria‐Targeted Photocytotoxicity. (28th July 2016)

• Record Type: Journal Article
• Authors: Mitra, Koushambi; Gautam, Srishti; Kondaiah, Paturu; Chakravarty, Akhil R.
• Is Part Of: ChemMedChem. Volume 11:Number 17(2016)
• Page Start: 1956
• Page End: 1967
• Publication Date: 2016-07-28
• Subjects: antitumor agents -- bioinorganic chemistry -- BODIPY -- platinum -- singlet oxygen; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600320
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Platinum(II) complexes of the type [Pt(L)(cat)] (1 and2 ), in which H2 cat is catechol and L represents two 2‐(2‐pyridyl)benzimidazole ligands with 4, 4‐difluoro‐4‐bora‐3a, 4a‐diaza‐ s ‐indacene (BODIPY) pendants, were synthesized to achieve mitochondria‐targeted photocytotoxicity. The complexes showed strong absorptions in the range λ =510–540 nm. Complex1 exhibited intense emission at λ =525 nm in 1 % DMSO/water solution (fluorescence quantum yield of 0.06). Nanosecond transient absorption spectral features indicated an enhanced population of the triplet excited state in di‐iodinated complex2 . The generation of singlet oxygen by complex2 upon exposure to visible light, as evidenced from experiments with 1, 3‐diphenylisobenzofuran, is suitable for photodynamic therapy because of the remarkable photosensitizing ability. The complexes resulted in excellent photocytotoxicity in HaCaT cells (half maximal inhibitory concentration IC50 ≈3 μm, λ =400–700 nm, light dose=10 J cm −2 ), but they remained non‐toxic in the dark (IC50 >100 μm ). Confocal microscopy images of1 and Pt estimation from isolated mitochondria showed colocalization of the complexes in the mitochondria. Complex2 displayed generation of reactive oxygen species induced by visible light, disruption of the mitochondrial membrane potential, and apoptosis. Abstract : Light on target : Platinum(II) catecholates with 4, 4‐difluoro‐4‐bora‐3a, 4a‐diaza‐ s ‐indacene (BODIPY)‐appended pyridylbenzimidazole ligands specifically target mitochondria. The complexes exhibit remarkable photocytotoxicity in visible light in HaCaT cells by causing apoptotic cell death through singlet oxygen species, yet they are non‐toxic in the dark. The emisssive BODIPY complex was used for cellular imaging, whereas the diiodo‐BODIPY analogue showed remarkable photodynamic therapy effects.