title: BODIPY-Appended 2-(2-Pyridyl)benzimidazole Platinum(II) Catecholates for Mitochondria-Targeted Photocytotoxicity.
abstract: Platinum(II) complexes of the type [Pt(L)(cat)] (1 and 2), 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. Complex 1 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 complex 2. The generation of singlet oxygen by complex 2 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 of 1 and Pt estimation from isolated mitochondria showed colocalization of the complexes in the mitochondria. Complex 2 displayed generation of reactive oxygen species induced by visible light, disruption of the mitochondrial membrane potential, and apoptosis.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors.forename: Koushambi
authors.initials: K
authors.lastname: Mitra
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors.forename: Srishti
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, Karnataka, India. paturu@mrdg.iisc.ernet.in.
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, Karnataka, India. arc@ipc.iisc.ernet.in.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D001896:Boron Compounds / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: C479869:2-(2'-pyridyl)benzimidazole; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001562:Benzimidazoles; D001896:Boron Compounds; D002396:Catechols; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents
keywords: BODIPY; antitumor agents; bioinorganic chemistry; platinum; singlet oxygen