Ruthenium(II) Conjugates of Boron-Dipyrromethene and Biotin for Targeted Photodynamic Therapy in Red Light

• Published in: Inorganic chemistry Vol. 59; no. 1; pp. 913 - 924
• Main Authors: Paul, Subhadeep, Kundu, Paramita, Bhattacharyya, Utso, Garai, Aditya, Maji, Ram Chandra, Kondaiah, Paturu, Chakravarty, Akhil R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.01.2020
• Subjects: A549 Cells; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biotin - chemistry; Biotin - pharmacology; Boron - chemistry; Boron - pharmacology; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Density Functional Theory; DNA Cleavage - drug effects; Drug Screening Assays, Antitumor; Humans; Light; Models, Molecular; Optical Imaging; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Porphobilinogen - analogs & derivatives; Porphobilinogen - chemistry; Porphobilinogen - pharmacology; Ruthenium - chemistry; Ruthenium - pharmacology
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.9b03178

The ruthenium­(II) complexes [RuCl­(L1)­(L3)]Cl (1), [RuCl­(L1)­(L4)]­Cl (2), [RuCl­(L2)­(L4)]Cl (3), [RuCl­(L1)­(L5)]Cl (4), and [RuCl­(L2)­(L5)]Cl (5) of NNN-donor dipicolylamine (dpa) bases (L4, L5) having BODIPY (boron-dipyrromethene) moieties, NN-donor phenanthroline derivatives (L1, L2), and benzyldipicolylamine (bzdpa, L3) were prepared and characterized by spectroscopic techniques and their cellular localization/uptake and photocytotoxicity studied. Complex 1, as its PF6 salt (1a), has been structurally characterized with help of a single-crystal X-ray diffraction technique. It has a RuN5Cl core with the Cl bonded trans to the amine nitrogen atom of bzdpa. The complexes showed intense absorption spectral bands near 500 nm (ε ≈ 58000 M–1 cm–1) in 2 and 3 and 654 nm (ε ≈ 80000 M–1 cm–1) in 4 and 5 in 1/1 DMSO/DPBS (v/v). Complex 5 having biotin and PEGylated-disteryl BODIPY gave a singlet oxygen quantum yield (ΦΔ) of ∼0.65 in DMSO. Complex 5 exhibited remarkable PDT (photodynamic therapy) activity (IC50 ≈ 0.02 μM) with a photocytotoxicity index (PI) value of >5000 in red light of 600–720 nm in A549 cancer cells. The biotin-conjugated complexes showed better photocytotoxicity in comparison to nonbiotinylated analogues in A549 cells. The complexes displayed less toxicity in HPL1D normal cells in comparison to A549 cancer cells. The emissive BODIPY complexes 3 and 5 (ΦF ≈ 0.07 in DMSO) showed significant mitochondrial localization.