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Light‐Tunable Generation of Singlet Oxygen and Nitric Oxide with a Bichromophoric Molecular Hybrid: a Bimodal Approach to Killing Cancer Cells
Author(s) -
Fraix Aurore,
Blangetti Marco,
Guglielmo Stefano,
Lazzarato Loretta,
Marino Nino,
Cardile Venera,
Graziano Adriana C. E.,
Manet Ilse,
Fruttero Roberta,
Gasco Alberto,
Sortino Salvatore
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500396
Subject(s) - singlet oxygen , chemistry , photosensitizer , photochemistry , conjugate , quantum yield , fluorescence , trifluoromethyl , nitro , photodynamic therapy , alkyl , oxygen , organic chemistry , mathematical analysis , physics , mathematics , quantum mechanics
The design, synthesis, photochemical properties, and biological evaluation of a novel photoactivatable bichromophoric conjugate are reported. The compound 1 , [4‐(4,4‐difluoro‐2,6‐diiodo‐1,3,5,7‐tetramethyl‐4‐bora‐3a,4a‐diaza‐ s ‐indacen‐8‐yl)‐ N ‐(3‐((4‐nitro‐3‐(trifluoromethyl)phenyl)amino)propyl)butanamide] combines a 2,6‐diiodo‐1,3,5,7‐tetramethyl BODIPY derivative as singlet oxygen ( 1 O 2 ) photosensitizer and 4‐nitro‐3‐(trifluoromethyl)aniline (NOPD) as nitric oxide (NO) photodonor, joined by an alkyl spacer. These two chromogenic units absorb in distinct regions of the visible spectrum, and their individual photochemical properties are conserved in the molecular conjugate. Irradiation of the bichromophoric conjugate with green light afforded 1 O 2 in high quantum yields, whereas 1 O 2 production was negligible with the use of blue light; under this latter condition, NO was released. Photogeneration of NO and cytotoxic 1 O 2 can therefore be regulated by appropriately tuning the excitation light wavelength and intensity. Tested on melanoma cancer cells, this resulted in amplified photomortality relative to that of a structurally correlated model compound 2 [4‐(4,4‐difluoro‐2,6‐diiodo‐1,3,5,7‐tetramethyl‐4‐bora‐3a,4a‐diaza‐ s ‐indacen‐8‐yl)‐ N ‐(3‐( p ‐tolylamino)propyl)butanamide] deprived of the NO‐release capacity. The cellular uptake of 1 , evaluated by confocal fluorescence microscopy, showed that the product is localized in the cytoplasm.